From: Subject: Guidelines for Preventing Opportunistic Infections Among Hematopoietic Stem Cell Transplant Recipients Date: Thu, 26 Oct 2006 11:40:08 +0300 MIME-Version: 1.0 Content-Type: multipart/related; boundary="----=_NextPart_000_0197_01C6F8F3.7CDB3540"; type="text/html" X-MimeOLE: Produced By Microsoft MimeOLE V5.50.4927.1200 This is a multi-part message in MIME format. ------=_NextPart_000_0197_01C6F8F3.7CDB3540 Content-Type: text/html; charset="Windows-1252" Content-Transfer-Encoding: quoted-printable Content-Location: http://www.cdc.gov/mmwr/preview/mmwrhtml/rr4910a1.htm Guidelines for Preventing Opportunistic Infections = Among Hematopoietic Stem Cell Transplant Recipients

Guidelines for Preventing Opportunistic Infections Among = Hematopoietic=20 Stem Cell Transplant Recipients

Recommendations of CDC, the Infectious Disease Society of = America, and=20 the American Society of Blood and Marrow Transplantation

Please note: = An=20 erratum has been published for this article. To view the erratum, = please=20 click here.<= /I>=20

Abbreviations Used in This Publication

ANC absolute neutrophil count

BAL bronchoalveolar lavage

CDA chlorodeoxyadenosine

CJD Creutzfeldt-Jakob disease

CMV cytomegalovirus

CRV community-acquired respiratory virus =

DNA deoxyribonucleic acid

EBV Epstein-Barr virus

EPA Environmental Protection Agency

FDA Food and Drug Administration

G-CSF granulocyte colony-stimulating factor = (filgastrim)=20

GM-CSF granulocyte-macrophage colony-stimulating = factor=20 (sargramostim)

GVHD graft-versus-host disease

HCW health-care worker

HEPA filter high-efficiency (>90%) particulate air = filter=20

Hib Haemophilus influenzae type b =

HIV human immunodeficiency virus

HLA human lymphocyte antigen

HSCT hematopoietic stem cell transplant; for this = report,=20 includes all blood- and marrow-derived hematopoietic stem = cell=20 transplants

HSV herpes simplex virus

HTLV human T-lymphotropic virus

IgA immunoglobulin A

IgG immunoglobulin G

IgM immunoglobulin M

IVIG intravenous immunoglobulin

LAF laminar air flow

LD Legionnaires' disease

LRI lower respiratory infection

MIC minimum inhibitory concentration

MRSA methicillin-resistant Staphylococcus = aureus=20

nvCJD new variant Creutzfeldt-Jakob disease =

OI opportunistic infection

PCP Pneumocystis carinii pneumonia =

PCR polymerase chain reaction

PZA/RIF pyrazinamide/rifampin

RNA ribonucleic acid

RSV respiratory syncytial virus

TB Mycobacteria tuberculosis

TMP-SMZ trimethoprim-sulfamethasaxole

TST tuberculin skin test

UCB umbilical cord blood

URI upper respiratory infection

VRE vancomycin-resistant Enterococcus =

VZIG varicella-zoster immunoglobulin

VZV varicella-zoster = virus

The following CDC staff members prepared this report: =

Clare A. Dykewicz, M.D., M.P.H.
Harold W. Jaffe, M.D.,=20 Director
Division of AIDS, STD, and TB Laboratory=20 Research
National Center for Infectious Diseases=20
Jonathan E. Kaplan, M.D.
Division of AIDS, STD, and TB = Laboratory=20 Research
National Center for Infectious Diseases
Division of = HIV/AIDS Prevention --- Surveillance and Epidemiology
National = Center=20 for HIV, STD, and TB Prevention=20
in collaboration with the Guidelines Working Group Members = from=20 CDC, the Infectious Disease Society of America, and the American = Society=20 of Blood and Marrow Transplantation

Clare A. Dykewicz, M.D., M.P.H., Chair
Harold W. Jaffe,=20 M.D.
Thomas J. Spira, M.D.
Division of AIDS, STD, and TB=20 Laboratory Research=20
William R. Jarvis, M.D.
Hospital Infections = Program
National=20 Center for Infectious Diseases, CDC=20
Jonathan E. Kaplan, M.D.
Division of AIDS, STD, and TB = Laboratory=20 Research
National Center for Infectious Diseases
Division of = HIV/AIDS Prevention --- Surveillance and Epidemiology
National = Center=20 for HIV, STD, and TB Prevention, CDC=20
Brian R. Edlin, M.D.
Division of HIV/AIDS=20 Prevention---Surveillance and Epidemiology
National Center for = HIV,=20 STD, and TB Prevention, CDC=20
Robert T. Chen, M.D., M.A.
Beth Hibbs, R.N.,=20 M.P.H.
Epidemiology and Surveillance Division
National=20 Immunization Program, CDC=20
Raleigh A. Bowden, M.D.
Keith Sullivan, M.D.
Fred = Hutchinson=20 Cancer Research Center
Seattle, Washington
David Emanuel, M.B.Ch.B.
Indiana = University
Indianapolis,=20 Indiana=20
David L. Longworth, M.D.
Cleveland Clinic=20 Foundation
Cleveland, Ohio=20
Philip A. Rowlings, M.B.B.S., M.S.
International Bone = Marrow=20 Transplant Registry/Autologous Blood and Marrow Transplant=20 Registry
Milwaukee, Wisconsin=20
Robert H. Rubin, M.D.
Massachusetts General = Hospital
Boston,=20 Massachusetts
and
Massachusetts Institute of=20 Technology
Cambridge, Massachusetts=20
Kent A. Sepkowitz, M.D.
Memorial-Sloan Kettering Cancer=20 Center
New York, New York=20
John R. Wingard, M.D.
University of = Florida
Gainesville,=20 Florida=20
Additional Contributors

John F. Modlin, M.D.
Dartmouth Medical School
Hanover, = New=20 Hampshire=20
Donna M. Ambrosino, M.D.
Dana-Farber Cancer = Institute
Boston,=20 Massachusetts=20
Norman W. Baylor, Ph.D.
Food and Drug=20 Administration
Rockville, Maryland=20
Albert D. Donnenberg, Ph.D.
University of=20 Pittsburgh
Pittsburgh, Pennsylvania
Pierce Gardner, M.D.
State University of New York at = Stony=20 Brook
Stony Brook, New York=20
Roger H. Giller, M.D.
University of Colorado
Denver,=20 Colorado=20
Neal A. Halsey, M.D.
Johns Hopkins = University
Baltimore,=20 Maryland=20
Chinh T. Le, M.D.
Kaiser-Permanente Medical = Center
Santa Rosa,=20 California=20
Deborah C. Molrine, M.D.
Dana-Farber Cancer = Institute
Boston,=20 Massachusetts=20
Keith M. Sullivan, M.D.
Fred Hutchinson Cancer Research=20 Center
Seattle, Washington=20
Summary

CDC, the Infectious Disease Society of America, and the = American=20 Society of Blood and Marrow Transplantation have cosponsored these = guidelines for preventing opportunistic infections (OIs) among=20 hematopoietic stem cell transplant (HSCT) recipients. The = guidelines were=20 drafted with the assistance of a working group of experts in = infectious=20 diseases, transplantation, and public health. For the purposes of = this=20 report, HSCT is defined as any transplantation of blood- or = marrow-derived=20 hematopoietic stem cells, regardless of transplant type (i.e., = allogeneic=20 or autologous) or cell source (i.e., bone marrow, peripheral = blood, or=20 placental or umbilical cord blood). Such OIs as bacterial, viral, = fungal,=20 protozoal, and helminth infections occur with increased frequency = or=20 severity among HSCT recipients. These evidence-based guidelines = contain=20 information regarding preventing OIs, hospital infection control,=20 strategies for safe living after transplantation, vaccinations, = and=20 hematopoietic stem cell safety. The disease-specific sections = address=20 preventing exposure and disease for pediatric and adult and = autologous and=20 allogeneic HSCT recipients. The goal of these guidelines is = twofold: to=20 summarize current data and provide evidence-based recommendations=20 regarding preventing OIs among HSCT patients. The guidelines were=20 developed for use by HSCT recipients, their household and close = contacts,=20 transplant and infectious diseases physicians, HSCT center = personnel, and=20 public health professionals. For all recommendations, prevention=20 strategies are rated by the strength of the recommendation and the = quality=20 of the evidence supporting the recommendation. Adhering to these=20 guidelines should reduce the number and severity of OIs among HSCT = recipients.=20
INTRODUCTION

In 1992, the Institute of Medicine (1) recommended that = CDC lead=20 a global effort to detect and control emerging infectious agents. = In=20 response, CDC published a plan (2) that outlined national = disease=20 prevention priorities, including the development of guidelines for = preventing opportunistic infections (OIs) among immunosuppressed = persons.=20 During 1995, CDC published guidelines for preventing OIs among = persons=20 infected with human immunodeficiency virus (HIV) and revised those = guidelines during 1997 and 1999 (3--5). Because of the = success of=20 those guidelines, CDC sought to determine the need for expanding = OI=20 prevention activities to other immunosuppressed populations. An = informal=20 survey of hematology, oncology, and infectious disease specialists = at=20 transplant centers and a working group formed by CDC determined = that=20 guidelines were needed to help prevent OIs among hematopoietic = stem cell=20 transplant (HSCT)* recipients.

The working group defined OIs as infections that occur with = increased=20 frequency or severity among HSCT recipients, and they drafted=20 evidence-based recommendations for preventing exposure to and = disease=20 caused by bacterial, fungal, viral, protozoal, or helminthic = pathogens.=20 During March 1997, the working group presented the first draft of = these=20 guidelines at a meeting of representatives from public and private = health=20 organizations. After review by that group and other experts, these = guidelines were revised and made available during September 1999 = for a=20 45-day public comment period after notification in the Federal=20 Register. Public comments were added when feasible, and the = report was=20 approved by CDC, the Infectious Disease Society of America, and = the=20 American Society of Blood and Marrow Transplantation. The = pediatric=20 content of these guidelines has been endorsed also by the American = Academy=20 of Pediatrics. The hematopoietic stem cell safety section was = endorsed by=20 the International Society of Hematotherapy and Graft Engineering. =

The first recommendations presented in this report are followed = by=20 recommendations for hospital infection control, strategies for = safe=20 living, vaccinations, and hematopoietic stem cell safety. Unless = otherwise=20 noted, these recommendations address allogeneic and autologous and = pediatric and adult HSCT recipients. Additionally, these = recommendations=20 are intended for use by the recipients, their household and other = close=20 contacts, transplant and infectious diseases specialists, HSCT = center=20 personnel, and public health professionals.

Using These Guidelines

For all recommendations, prevention strategies are rated by the = strength of the recommendation (Table= =20 1) and the quality of the evidence (Table= =20 2) supporting the recommendation. The principles of this = rating system=20 were developed by the Infectious Disease Society of America and = the U.S.=20 Public Health Service for use in the guidelines for preventing OIs = among=20 HIV-infected persons (3--6). This rating system allows = assessments=20 of recommendations to which adherence is critical.=20
BACKGROUND

HSCT is the infusion of hematopoietic stem cells from a donor = into a=20 patient who has received chemotherapy, which is usually = marrow-ablative.=20 Increasingly, HSCT has been used to treat neoplastic diseases, = hematologic=20 disorders, immunodeficiency syndromes, congenital enzyme = deficiencies, and=20 autoimmune disorders (e.g., systemic lupus erythematosus or = multiple=20 sclerosis) (7--10). Moreover, HSCT has become standard = treatment=20 for selected conditions (7,11,12). Data from the = International Bone=20 Marrow Transplant Registry and the Autologous Blood and Marrow = Transplant=20 Registry indicate that approximately 20,000 HSCTs were performed = in North=20 America during 1998 (Statistical Center of the International Bone = Marrow=20 Transplant Registry and Autologous Blood and Marrow Transplant = Registry,=20 unpublished data, 1998).

HSCTs are classified as either allogeneic or autologous on the = basis of=20 the source of the transplanted hematopoietic progenitor cells. = Cells used=20 in allogeneic HSCTs are harvested from a donor other than the = transplant=20 recipient. Such transplants are the most effective treatment for = persons=20 with severe aplastic anemia (13) and offer the only = curative=20 therapy for persons with chronic myelogenous leukemia (12). = Allogeneic donors might be a blood relative or an unrelated donor. = Allogeneic transplants are usually most successful when the donor = is a=20 human lymphocyte antigen (HLA)-identical twin or matched sibling. = However,=20 for allogeneic candidates who lack such a donor, registry = organizations=20 (e.g., the National Marrow Donor Program) maintain computerized = databases=20 that store information regarding HLA type from millions of = volunteer=20 donors (14--16). Another source of stem cells for = allogeneic=20 candidates without an HLA-matched sibling is a mismatched family = member=20 (17,18). However, persons who receive allogeneic grafts = from donors=20 who are not HLA-matched siblings are at a substantially greater = risk for=20 graft-versus-host disease (GVHD) (19). These persons are = also at=20 increased risk for suboptimal graft function and delayed immune = system=20 recovery (19). To reduce GVHD among allogeneic HSCTs, = techniques=20 have been developed to remove T-lymphocytes, the principal = effectors of=20 GVHD, from the donor graft. Although the recipients of=20 T-lymphocyte--depleted marrow grafts generally have lower rates of = GVHD,=20 they also have greater rates of graft rejection, cytomegalovirus = (CMV)=20 infection, invasive fungal infection, and Epstein-Barr virus=20 (EBV)-associated posttransplant lymphoproliferative disease = (20).=20

The patient's own cells are used in an autologous HSCT. Similar = to=20 autologous transplants are syngeneic transplants, among whom the=20 HLA-identical twin serves as the donor. Autologous HSCTs are = preferred for=20 patients who require high-level or marrow-ablative chemotherapy to = eradicate an underlying malignancy but have healthy, undiseased = bone=20 marrows. Autologous HSCTs are also preferred when the immunologic=20 antitumor effect of an allograft is not beneficial. Autologous = HSCTs are=20 used most frequently to treat breast cancer, non-Hodgkin's = lymphoma, and=20 Hodgkin's disease (21). Neither autologous nor syngeneic = HSCTs=20 confer a risk for chronic GVHD.

Recently, medical centers have begun to harvest hematopoietic = stem=20 cells from placental or umbilical cord blood (UCB) immediately = after=20 birth. These harvested cells are used primarily for allogeneic = transplants=20 among children. Early results demonstrate that greater degrees of=20 histoincompatibility between donor and recipient might be = tolerated=20 without graft rejection or GVHD when UCB hematopoietic cells are = used=20 (22--24). However, immune system function after UCB = transplants has=20 not been well-studied.

HSCT is also evolving rapidly in other areas. For example,=20 hematopoietic stem cells harvested from the patient's peripheral = blood=20 after treatment with hematopoietic colony-stimulating factors = (e.g.,=20 granulocyte colony-stimulating factor [G-CSF or filgastrim] or=20 granulocyte-macrophage colony-stimulating factor [GM-CSF or = sargramostim])=20 are being used increasingly among autologous recipients = (25) and=20 are under investigation for use among allogeneic HSCT. Peripheral = blood=20 has largely replaced bone marrow as a source of stem cells for = autologous=20 recipients. A benefit of harvesting such cells from the donor's = peripheral=20 blood instead of bone marrow is that it eliminates the need for = general=20 anesthesia associated with bone marrow aspiration.

GVHD is a condition in which the donated cells recognize the=20 recipient's cells as nonself and attack them. Although the use of=20 intravenous immunoglobulin (IVIG) in the routine management of = allogeneic=20 patients was common in the past as a means of producing immune = modulation=20 among patients with GVHD, this practice has declined because of = cost=20 factors (26) and because of the development of other = strategies for=20 GVHD prophylaxis (27). For example, use of cyclosporine = GVHD=20 prophylaxis has become commonplace since its introduction during = the early=20 1980s. Most frequently, cyclosporine or tacrolimus (FK506) is = administered=20 in combination with other immunosuppressive agents (e.g., = methotrexate or=20 corticosteroids) (27). Although cyclosporine is effective = in=20 preventing GVHD, its use entails greater hazards for infectious=20 complications and relapse of the underlying neoplastic disease for = which=20 the transplant was performed.

Although survival rates for certain autologous recipients have = improved=20 (28,29), infection remains a leading cause of death among=20 allogeneic transplants and is a major cause of morbidity among = autologous=20 HSCTs (29). Researchers from the National Marrow Donor = Program=20 reported that, of 462 persons receiving unrelated allogeneic HSCTs = during=20 December 1987--November 1990, a total of 66% had died by 1991 = (15).=20 Among primary and secondary causes of death, the most common cause = was=20 infection, which occurred among 37% of 307 patients (15).** =

Despite high morbidity and mortality after HSCT, recipients who = survive=20 long-term are likely to enjoy good health. A survey of 798 persons = who had=20 received an HSCT before 1985 and who had survived for >5 years = after=20 HSCT, determined that 93% were in good health and that 89% had = returned to=20 work or school full time (30). In another survey of 125 = adults who=20 had survived a mean of 10 years after HSCT, 88% responded that the = benefits of transplantation outweighed the side effects = (31).

Immune System Recovery After HSCT

During the first year after an HSCT, recipients typically = follow a=20 predictable pattern of immune system deficiency and recovery, = which begins=20 with the chemotherapy or radiation therapy (i.e., the conditioning = regimen) administered just before the HSCT to treat the underlying = disease. Unfortunately, this conditioning regimen also destroys = normal=20 hematopoiesis for neutrophils, monocytes, and macrophages and = damages=20 mucosal progenitor cells, causing a temporary loss of mucosal = barrier=20 integrity. The gastrointestinal tract, which normally contains = bacteria,=20 commensal fungi, and other bacteria-carrying sources (e.g., skin = or=20 mucosa) becomes a reservoir of potential pathogens. Virtually all = HSCT=20 recipients rapidly lose all T- and B-lymphocytes after = conditioning,=20 losing immune memory accumulated through a lifetime of exposure to = infectious agents, environmental antigens, and vaccines. Because = transfer=20 of donor immunity to HSCT recipients is variable and influenced by = the=20 timing of antigen exposure among donor and recipient, passively = acquired=20 donor immunity cannot be relied upon to provide long-term immunity = against=20 infectious diseases among HSCT recipients.

During the first month after HSCT, the major host-defense = deficits=20 include impaired phagocytosis and damaged mucocutaneous barriers.=20 Additionally, indwelling intravenous catheters are frequently = placed and=20 left in situ for weeks to administer parenteral medications, blood = products, and nutritional supplements. These catheters serve as = another=20 portal of entry for opportunistic pathogens from organisms = colonizing the=20 skin (e.g., . coagulase-negative=20 Staphylococci, Staphylococcus aureus, Candida = species, and Enterococci) (32,33).

Engraftment for adults and children is defined as the point at = which a=20 patient can maintain a sustained absolute neutrophil count (ANC) = of=20 >500/mm³ and sustained platelet count of = >20,000,=20 lasting >3 consecutive days without transfusions. Among=20 unrelated allogeneic recipients, engraftment occurs at a median of = 22 days=20 after HSCT (range: 6--84 days) (15). In the absence of=20 corticosteroid use, engraftment is associated with the restoration = of=20 effective phagocytic function, which results in a decreased risk = for=20 bacterial and fungal infections. However, all HSCT recipients and=20 particularly allogeneic recipients, experience an immune system=20 dysfunction for months after engraftment. For example, although = allogeneic=20 recipients might have normal total lymphocyte counts within = >2=20 months after HSCT, they have abnormal CD4/CD8 T-cell ratios, = reflecting=20 their decreased CD4 and increased CD8 T-cell counts (27). = They=20 might also have immunoglobulin G (IgG)₂, = IgG₄, and=20 immunoglobulin A (IgA) deficiencies for months after HSCT and have = difficulty switching from immunoglobulin M (IgM) to IgG production = after=20 antigen exposure (32). Immune system recovery might be = delayed=20 further by CMV infection (34).

During the first >2 months after HSCT, recipients = might=20 experience acute GVHD that manifests as skin, gastrointestinal, = and liver=20 injury, and is graded on a scale of I--IV (32,35,36). = Although=20 autologous or syngeneic recipients might occasionally experience a = mild,=20 self-limited illness that is acute GVHD-like (19,37), GVHD = occurs=20 primarily among allogeneic recipients, particularly those = receiving=20 matched, unrelated donor transplants. GVHD is a substantial risk = factor=20 for infection among HSCT recipients because it is associated with = a=20 delayed immunologic recovery and prolonged immunodeficiency = (19).=20 Additionally, the immunosuppressive agents used for GVHD = prophylaxis and=20 treatment might make the HSCT recipient more vulnerable to = opportunistic=20 viral and fungal pathogens (38).

Certain patients, particularly adult allogeneic recipients, = might also=20 experience chronic GVHD, which is graded as either limited or = extensive=20 chronic GVHD (19,39). Chronic GVHD appears similar to = autoimmune,=20 connective-tissue disorders (e.g., scleroderma or systemic lupus=20 erythematosus) (40) and is associated with cellular and = humoral=20 immunodeficiencies, including macrophage deficiency, impaired = neutrophil=20 chemotaxis (41), poor response to vaccination = (42--44), and=20 severe mucositis (19). Risk factors for chronic GVHD = include=20 increasing age, allogeneic HSCT (particularly those among whom the = donor=20 is unrelated or a non-HLA identical family member) (40), = and a=20 history of acute GVHD (24,45). Chronic GVHD was first = described as=20 occurring >100 days after HSCT but can occur 40 days after HSCT = (19). Although allogeneic recipients with chronic GVHD have = normal=20 or high total serum immunoglobulin levels (41), they = experience=20 long-lasting IgA, IgG, and IgG subclass deficiencies = (41,46,47) and=20 poor opsonization and impaired reticuloendothelial function. = Consequently,=20 they are at even greater risk for infections (32,39), = particularly=20 life-threatening bacterial infections from encapsulated organisms = (e.g.,=20 Stre. pneumoniae, Ha. influenzae, or Ne.=20 meningitidis). After chronic GVHD resolves, which might take = years,=20 cell-mediated and humoral immunity function are gradually = restored.

Opportunistic Pathogens After HSCT

HSCT recipients experience certain infections at different = times=20 posttransplant, reflecting the predominant host-defense defect(s) = (Figur= e).=20 Immune system recovery for HSCT recipients takes place in three = phases=20 beginning at day 0, the day of transplant. Phase I is the = preengraftment=20 phase (<30 days after HSCT); phase II, the postengraftment = phase=20 (30--100 days after HSCT); and phase III, the late phase (>100 = days=20 after HSCT). Prevention strategies should be based on these three = phases=20 and the following information:=20

Phase I, preengraftment. During the first month=20 posttransplant, HSCT recipients have two critical risk factors = for=20 infection --- prolonged neutropenia and breaks in the = mucocutaneous=20 barrier resulting from the HSCT preparative regimens and = frequent=20 vascular access required for patient care. Consequently, oral,=20 gastro-intestinal, and skin flora are sources of infection. = Prevalent=20 pathogens include Candida species, and as neutropenia = continues,=20 Aspergillus species. Additionally, herpes simplex virus = (HSV)=20 reactivation can occur during this phase. During preengraftment, = the=20 risks for infection are the same for autologous or allogeneic = patients,=20 and OIs can appear as febrile neutropenia. Although a = recipient's first=20 fever during preengraftment is probably caused by a bacterial = pathogen,=20 rarely is an organism or site of infection identified. Instead, = such=20 infections are usually treated preemptively or empirically = (48)=20 until the neutropenia resolves (49). Growth factors can = be=20 administered during phase I to decrease neutropenia duration and = complications (e.g., febrile neutropenia) (50).=20
Phase II, postengraftment. Phase II is dominated by = impaired=20 cell-mediated immunity for allogeneic or autologous recipients. = Scope=20 and impact of this defect for allogeneic recipients are = determined by=20 the extent of GVHD and its immunosuppressive therapy. After = engraftment,=20 the herpes viruses, particularly CMV, are critical pathogens. At = 30--100=20 days after HSCT, CMV causes pneumonia, hepatitis, and colitis = and=20 potentiates superinfection with opportunistic pathogens, = particularly=20 among patients with active GVHD. Other dominant pathogens during = this=20 phase include Pneumocystis carinii and Aspergillus = species.=20
Phase III, late phase. During phase III, autologous=20 recipients usually have more rapid recovery of immune system = function=20 and, therefore, a lower risk for OIs than do allogeneic = recipients.=20 Because of cell-mediated and humoral immunity defects and = impaired=20 reticuloendothelial system function, allogeneic patients with = chronic=20 GVHD and recipients of alternate donor allogeneic transplants = are at=20 risk for certain infections during this phase. Alternate donors = include=20 matched unrelated, UCB, or mismatched family-related donors. = These=20 patients are at risk for infections that include CMV, = varicella-zoster=20 virus (VZV), EBV-related posttransplant lymphoproliferative = disease,=20 community-acquired respiratory viruses (CRV), and infections = with=20 encapsulated bacteria (e.g., Ha. influenzae and Stre.=20 pneumoniae). Risk for these infections is approximately = proportional=20 to the severity of the patient's GVHD during phases II and III. = Patients=20 receiving mismatched allogeneic transplants have a higher attack = rate=20 and severity of GVHD and, therefore, a higher risk for OIs = during phases=20 II and III than do patients receiving matched allogeneic HSCTs. = In=20 contrast, patients undergoing autologous transplantation are = primarily=20 at risk for infection during phase I.

Preventing infections among HSCT recipients is preferable to = treating=20 infections. How ever, despite recent technologic advances, more = research=20 is needed to optimize health outcomes for HSCT recipients. Efforts = to=20 improve immune system reconstitution, particularly among = allogeneic=20 transplant recipients, and to prevent or resolve the immune = dysregulation=20 resulting from donor-recipient histoincompatibility and GVHD = remain=20 substantial challenges for preventing recurrent, persistent, or=20 progressive infections among HSCT patients.=20
BACTERIAL INFECTIONS

General Recommendations

Preventing Exposure

Because bacteria are carried on the hands, health-care workers = (HCWs)=20 and others in contact with HSCT recipients should routinely follow = appropriate hand-washing practices to avoid exposing recipients to = bacterial pathogens (AIII).

Preventing Disease

Preventing Early Disease (0--100 Days After = HSCT).=20 Routine gut decontamination is not recommended for HSCT candidates = (51--53) (DIII). Because of limited data, no recommendations can = be made=20 regarding the routine use of antibiotics for bacterial prophylaxis = among=20 afebrile, asymptomatic neutropenic recipients. Although studies = have=20 reported that using prophylactic antibiotics might reduce = bacteremia rates=20 after HSCT (51), infection-related fatality rates are not reduced = (52). If=20 physicians choose to use prophylactic antibiotics among = asymptomatic,=20 afebrile, neutropenic recipients, they should routinely review = hospital=20 and HSCT center antibiotic-susceptibility profiles, particularly = when=20 using a single antibiotic for antibacterial prophylaxis (BIII). = The=20 emergence of fluoquinolone-resistant coagulase-negative=20 Staphylococci and Es. coli (51,52), = vancomycin-intermediate=20 Sta. aureus and vancomycin-resistant Enterococcus = (VRE) are=20 increasing concerns (54). Vancomycin should not be used as an = agent for=20 routine bacterial prophylaxis (DIII). Growth factors (e.g., GM-CSF = and=20 G-CSF) shorten the duration of neutropenia after HSCT (55); = however, no=20 data were found that indicate whether growth factors effectively = reduce=20 the attack rate of invasive bacterial disease.

Physicians should not routinely administer IVIG products to = HSCT=20 recipients for bacterial infection prophylaxis (DII), although = IVIG has=20 been recommended for use in producing immune system modulation for = GVHD=20 prevention. Researchers have recommended routine IVIG*** use to = prevent=20 bacterial infections among the approximately 20%--25% of HSCT = recipients=20 with unrelated marrow grafts who experience severe = hypogamma-globulinemia=20 (e.g., IgG < 400 mg/dl) within the first 100 days after = transplant=20 (CIII). For example, recipients who are hypogammaglobulinemic = might=20 receive prophylactic IVIG to prevent bacterial sinopulmonary = infections=20 (e.g., from Stre. pneumoniae) (8) (CIII). For=20 hypogammaglobulinemic allogeneic recipients, physicians can use a = higher=20 and more frequent dose of IVIG than is standard for non-HSCT = recipients=20 because the IVIG half-life among HSCT recipients (generally 1--10 = days) is=20 much shorter than the half-life among healthy adults (generally = 18--23=20 days) (56--58). Additionally, infections might accelerate = IgG=20 catabolism; therefore, the IVIG dose for a hypogammaglobulinemic = recipient=20 should be individualized to maintain trough serum IgG = concentrations=20 >400--500 mg/dl (58) (BII). Consequently, physicians = should=20 monitor trough serum IgG concentrations among these patients = approximately=20 every 2 weeks and adjust IVIG doses as needed (BIII) (Appen= dix).=20

Preventing Late Disease (>100 Days After = HSCT).=20 Antibiotic prophylaxis is recommended for preventing infection = with=20 encapsulated organisms (e.g., Stre. pneumoniae, Ha.=20 influenzae, or Ne. meningitidis) among allogeneic = recipients=20 with chronic GVHD for as long as active chronic GVHD treatment is=20 administered (59) (BIII). Antibiotic selection should be = guided by=20 local antibiotic resistance patterns. In the absence of severe=20 demonstrable hypogammaglobulinemia (e.g., IgG levels < 400 = mg/dl, which=20 might be associated with recurrent sinopulmonary infections), = routine=20 monthly IVIG administration to HSCT recipients >90 days after = HSCT is=20 not recommended (60) (DI) as a means of preventing = bacterial=20 infections.

Other Disease Prevention Recommendations. Routine = use of=20 IVIG among autologous recipients is not recommended (61) = (DII).=20 Recommendations for preventing bacterial infections are the same = among=20 pediatric or adult HSCT recipients.

Recommendations Regarding Stre. pneumoniae

Preventing Exposure

Appropriate care precautions should be taken with hospitalized = patients=20 infected with Stre. pneumoniae (62,63) (BIII) to = prevent=20 exposure among HSCT recipients.

Preventing Disease

Information regarding the currently available 23-valent = pneumococcal=20 polysaccharide vaccine indicates limited immunogenicity among HSCT = recipients. However, because of its potential benefit to certain = patients,=20 it should be administered to HSCT recipients at 12 and 24 months = after=20 HSCT (64--66) (BIII). No data were found regarding safety = and=20 immunogenicity of the 7-valent conjugate pneumococcal vaccine = among HSCT=20 recipients; therefore, no recommendation regarding use of this = vaccine can=20 be made.

Antibiotic prophylaxis is recommended for preventing infection = with=20 encapsulated organisms (e.g., Stre. pneumoniae, Ha.=20 influenzae, and Ne. meningitidis) among allogeneic = recipients=20 with chronic GVHD for as long as active chronic GVHD treatment is=20 administered (59) (BIII). Trimethoprim-sulfamethasaxole = (TMP-SMZ)=20 administered for Pneumocystis carinii pneumonia (PCP) = prophylaxis=20 will also provide protection against pneumococcal infections. = However, no=20 data were found to support using TMP-SMZ prophylaxis among HSCT = recipients=20 solely for the purpose of preventing Stre. pneumoniae = disease.=20 Certain strains of Stre. pneumoniae are resistant to = TMP-SMZ and=20 penicillin. Recommendations for preventing pneumococcal infections = are the=20 same for allogeneic or autologous recipients.

As with adults, pediatric HSCT recipients aged >2 = years=20 should be administered the current 23-valent pneumococcal = polysaccharide=20 vaccine because the vaccine can be effective (BIII). However, this = vaccine=20 should not be administered to children aged <2 years because it = is not=20 effective among that age population (DI). No data were found = regarding=20 safety and immunogenicity of the 7-valent conjugate pneumococcal = vaccine=20 among pediatric HSCT recipients; therefore, no recommendation = regarding=20 use of this vaccine can be made.

Recommendations Regarding Streptococci viridans =

Preventing Exposure

Because Streptococci viridans colonize the oropharynx = and gut,=20 no effective method of preventing exposure is known.

Preventing Disease

Chemotherapy-induced oral mucositis is a potential source of=20 Streptococci viridans bacteremia. Consequently, before = conditioning=20 starts, dental consults should be obtained for all HSCT candidates = to=20 assess their state of oral health and to perform any needed dental = procedures to decrease the risk for oral infections after = transplant=20 (67) (AIII).

Generally, HSCT physicians should not use prophylactic = antibiotics to=20 prevent Streptococci viridans infections (DIII). No data = were found=20 that demonstrate efficacy of prophylactic antibiotics for this = infection.=20 Furthermore, such use might select antibiotic-resistant bacteria, = and in=20 fact, penicillin- and vancomycin-resistant strains of = Streptococci=20 viridans have been reported (68). However, when = Streptococci=20 viridans infections among HSCT recipients are virulent and = associated=20 with overwhelming sepsis and shock in an institution, prophylaxis = might be=20 evaluated (CIII). Decisions regarding the use of Streptococci=20 viridans prophylaxis should be made only after consultation = with the=20 hospital epidemiologists or infection-control practitioners who = monitor=20 rates of nosocomial bacteremia and bacterial susceptibility = (BIII).

HSCT physicians should be familiar with current antibiotic=20 susceptibilities for patient isolates from their HSCT centers, = including=20 Streptococci viridans (BIII). Physicians should maintain a = high=20 index of suspicion for this infection among HSCT recipients with=20 symptomatic mucositis because early diagnosis and aggressive = therapy are=20 currently the only potential means of preventing shock when = severely=20 neutropenic HSCT recipients experience Streptococci = viridans=20 bacteremia (69).

Recommendations Regarding Ha. influenzae type b =

Preventing Exposure

Adults with Ha. influenzae type b (Hib) pneumonia = require=20 standard precautions (62) to prevent exposing the HSCT = recipient to=20 Hib. Adults and children who are in contact with the HSCT = recipient and=20 who have known or suspected invasive Hib disease, including = meningitis,=20 bacteremia, or epiglottitis, should be placed in droplet = precautions until=20 24 hours after they begin appropriate antibiotic therapy, after = which they=20 can be switched to standard precautions. Household contacts = exposed to=20 persons with Hib disease and who also have contact with HSCT = recipients=20 should be administered rifampin prophylaxis according to published = recommendations (70,71); prophylaxis for household contacts = of a=20 patient with Hib disease are necessary if all contacts aged <4 = years=20 are not fully vaccinated (BIII) (Appen= dix).=20 This recommendation is critical because the risk for invasive Hib = disease=20 among unvaccinated household contacts aged <4 years is = increased, and=20 rifampin can be effective in eliminating Hib carriage and = preventing=20 invasive Hib disease (72--74). Pediatric household contacts = should=20 be up-to-date with Hib vaccinations to prevent possible Hib = exposure to=20 the HSCT recipient (AII).

Preventing Disease

Although no data regarding vaccine efficacy among HSCT = recipients were=20 found, Hib conjugate vaccine should be administered to HSCT = recipients at=20 12, 14, and 24 months after HSCT (BII). This vaccine is = recommended=20 because the majority of HSCT recipients have low levels of Hib = capsular=20 polysaccharide antibodies >4 months after HSCT = (75), and=20 allogeneic recipients with chronic GVHD are at increased risk for=20 infection from encapsulated organisms (e.g., Hib) (76,77). = HSCT=20 recipients who are exposed to persons with Hib disease should be = offered=20 rifampin prophylaxis according to published recommendations = (70)=20 (BIII) (Appen= dix).=20

Antibiotic prophylaxis is recommended for preventing infection = with=20 encapsulated organisms (e.g., Stre. pneumoniae, Ha.=20 influenzae, or Ne. meningitidis) among allogeneic = recipients=20 with chronic GVHD for as long as active chronic GVHD treatment is=20 administered (59) (BIII). Antibiotic selection should be = guided by=20 local antibiotic-resistance patterns. Recommendations for = preventing Hib=20 infections are the same for allogeneic or autologous recipients.=20 Recommendations for preventing Hib disease are the same for = pediatric or=20 adult HSCT recipients, except that any child infected with Hib = pneumonia=20 requires standard precautions with droplet precautions added for = the first=20 24 hours after beginning appropriate antibiotic therapy = (62,70)=20 (BIII). Appropriate pediatric doses should be administered for Hib = conjugate vaccine and for rifampin prophylaxis (71) (Appen= dix).=20
VIRAL INFECTIONS

Recommendations Regarding Cytomegalovirus

Preventing Exposure

HSCT candidates should be tested for the presence of serum = anti-CMV IgG=20 antibodies before transplantation to determine their risk for = primary CMV=20 infection and reactivation after HSCT (AIII). Only Food and Drug=20 Administration (FDA) licensed or approved tests should be used. = HSCT=20 recipients and candidates should avoid sharing cups, glasses, and = eating=20 utensils with others, including family members, to decrease the = risk for=20 CMV exposure (BIII).

Sexually active patients who are not in long-term monogamous=20 relationships should always use latex condoms during sexual = contact to=20 reduce their risk for exposure to CMV and other sexually = transmitted=20 pathogens (AII). However, even long-time monogamous pairs can be=20 discordant for CMV infections. Therefore, during periods of=20 immuno-compromise, sexually active HSCT recipients in monogamous=20 relationships should ask partners to be tested for serum CMV IgG = antibody,=20 and discordant couples should use latex condoms during sexual = contact to=20 reduce the risk for exposure to this sexually transmitted OI = (CIII).

After handling or changing diapers or after wiping oral and = nasal=20 secretions, HSCT candidates and recipients should practice regular = hand=20 washing to reduce the risk for CMV exposure (AII). = CMV-seronegative=20 recipients of allogeneic stem cell transplants from = CMV-seronegative=20 donors (i.e., R-negative or D-negative) should receive only=20 leukocyte-reduced or CMV-seronegative red cells or = leukocyte-reduced=20 platelets (<1 x 10⁶ leukocytes/unit) to prevent=20 transfusion-associated CMV infection (78) (AI). However,=20 insufficient data were found to recommend use of leukocyte-reduced = or=20 CMV-seronega tive red cells and platelets among CMV-seronegative=20 recipients who have CMV-seropositive donors (i.e., R-negative or=20 D-positive).

All HCWs should wear gloves when handling blood products or = other=20 potentially contaminated biologic materials (AII) to prevent = transmission=20 of CMV to HSCT recipients. HSCT patients who are known to excrete = CMV=20 should be placed under standard precautions (62) for the = duration=20 of CMV excretion to avoid possible transmission to = CMV-seronegative HSCT=20 recipients and candidates (AIII). Physicians are cautioned that = CMV=20 excretion can be episodic or prolonged.

Preventing Disease and Disease Recurrence

HSCT recipients at risk for CMV disease after HSCT (i.e., all=20 CMV-seropositive HSCT recipients, and all CMV-seronegative = recipients with=20 a CMV-seropositive donor) should be placed on a CMV disease = prevention=20 program from the time of engraftment until 100 days after HSCT = (i.e.,=20 phase II) (AI). Physicians should use either prophylaxis or = preemptive=20 treatment with ganciclovir for allogeneic recipients (AI). In = selecting a=20 CMV disease prevention strategy, physicians should assess the = risks and=20 benefits of each strategy, the needs and condition of the patient, = and the=20 hospital's virology laboratory support capability.

Prophylaxis strategy against early CMV (i.e., <100 days = after HSCT)=20 for allogeneic recipients involves administering ganciclovir = prophylaxis=20 to all allogeneic recipients at risk throughout phase II (i.e., = from=20 engraftment to 100 days after HSCT). The induction course is = usually=20 started at engraftment (AI), although physicians can add a brief=20 prophylactic course during HSCT preconditioning (CIII) (Appen= dix).=20

Preemptive strategy against early CMV (i.e., <100 days after = HSCT)=20 for allogeneic recipients is preferred over prophylaxis for=20 CMV-seronegative HSCT recipients of seropositive donor cells = (i.e.,=20 D-positive or R-negative) because of the low attack rate of active = CMV=20 infection if screened or filtered blood product support is used = (BII).=20 Preemptive strategy restricts ganciclovir use for those patients = who have=20 evidence of CMV infection after HSCT. It requires the use of = sensitive and=20 specific laboratory tests to rapidly diagnose CMV infection after = HSCT and=20 to enable immediate administration of ganciclovir after CMV = infection has=20 been detected. Allogeneic recipients at risk should be screened=20 >1 times/week from 10 days to 100 days after HSCT (i.e., = phase=20 II) for the presence of CMV viremia or antigenemia (AIII).

HSCT physicians should select one of two diagnostic tests to = determine=20 the need for preemptive treatment. Currently, the detection of CMV = pp65=20 antigen in leukocytes (antigenemia) (79,80) is preferred = for=20 screening for preemptive treatment because it is more rapid and = sensitive=20 than culture and has good positive predictive value = (79--81).=20 Direct detection of CMV-DNA (deoxyribonucleic acid) by polymerase = chain=20 reaction (PCR) (82) is very sensitive but has a low = positive=20 predictive value (79). Although CMV-DNA PCR is less = sensitive than=20 whole blood or leukocyte PCR, plasma CMV-DNA PCR is useful during=20 neutropenia, when the number of leukocytes/slide is too low to = allow CMV=20 pp65 antigenemia testing.

Virus culture of urine, saliva, blood, or bronchoalveolar = washings by=20 rapid shell-vial culture (83) or routine culture = (84,85) can=20 be used; however, viral culture techniques are less sensitive than = CMV-DNA=20 PCR or CMV pp65 antigenemia tests. Also, rapid shell-viral = cultures=20 require >48 hours and routine viral cultures can require = weeks=20 to obtain final results. Thus, viral culture techniques are less=20 satisfactory than PCR or antigenemia tests. HSCT centers without = access to=20 PCR or antigenemia tests should use prophylaxis rather than = preemptive=20 therapy for CMV disease prevention (86) (BII). Physicians = do use=20 other diagnostic tests (e.g., hybrid capture CMV-DNA assay, = Version 2.0=20 [87] or CMV pp67 viral RNA [ribonucleic acid] detection)=20 (88); however, limited data were found regarding use among = HSCT=20 recipients, and therefore, no recommendation for use can be made. =

Allogeneic recipients <100 days after HSCT (i.e., = during=20 phase II) should begin preemptive treatment with ganciclovir if = CMV=20 viremia or any antigenemia is detected or if the recipient has=20 >2 consecutively positive CMV-DNA PCR tests (BIII). = After=20 preemptive treatment has been started, maintenance ganciclovir is = usually=20 continued until 100 days after HSCT or for a minimum of 3 weeks, = whichever=20 is longer (AI) (Appen= dix).=20 Antigen or PCR tests should be negative when ganciclovir is = stopped.=20 Studies report that a shorter course of ganciclovir (e.g., for 3 = weeks or=20 until negative PCR or antigenemia occurs) (89--91) might = provide=20 adequate CMV prevention with less toxicity, but routine weekly = screening=20 by pp65 antigen or PCR test is necessary after stopping = ganciclovir=20 because CMV reactivation can occur (BIII).

Presently, only the intravenous formulation of ganciclovir has = been=20 approved for use in CMV prophylactic or preemptive strategies = (BIII). No=20 recommendation for oral ganciclovir use among HSCT recipients can = be made=20 because clinical trials evaluating its efficacy are still in = progress. One=20 group has used ganciclovir and foscarnet on alternate days for CMV = prevention (92), but no recommendation can be made = regarding this=20 strategy because of limited data. Patients who are = ganciclovir-intolerant=20 should be administered foscarnet instead (93) (BII) (Appen= dix).=20 HSCT recipients receiving ganciclovir should have ANCs checked=20 >2 times/week (BIII). Researchers report managing=20 ganciclovir-associated neutropenia by adding G-CSF (94) or=20 temporarily stopping ganciclovir for >2 days if the = patient's=20 ANC is <1,000 (CIII). Ganciclovir can be restarted when the = patient's=20 ANC is >1,000 for 2 consecutive days. Alternatively, = researchers=20 report substituting foscarnet for ganciclovir if a) the HSCT = recipient is=20 still CMV viremic or antigenemic or b) the ANC remains <1,000 = for >5=20 days after ganciclovir has been stopped (CIII) (Appen= dix).=20 Because neutropenia accompanying ganciclovir administration is = usually=20 brief, such patients do not require antifungal or antibacterial=20 prophylaxis (DIII).

Currently, no benefit has been reported from routinely = administering=20 ganciclovir prophylaxis to all HSCT recipients at >100 days = after HSCT=20 (i.e., during phase III). However, persons with high risk for late = CMV=20 disease should be routinely screened biweekly for evidence of CMV=20 reactivation as long as substantial immunocompromise persists = (BIII). Risk=20 factors for late CMV disease include allogeneic HSCT accompanied = by=20 chronic GVHD, steroid use, low CD4 counts, delay in high avidity = anti-CMV=20 antibody, and recipients of matched unrelated or T-cell--depleted = HSCTs=20 who are at high risk (95--99). If CMV is still detectable = by=20 routine screening >100 days after HSCT, ganciclovir = should be=20 continued until CMV is no longer detectable (AI). If low-grade CMV = antigenemia (<5 positive cells/slide) is detected on routine = screening,=20 the antigenemia test should be repeated in 3 days (BIII). If CMV=20 antigenemia indicates >5 cells/slide, PCR is positive, = or the=20 shell-vial culture detects CMV viremia, a 3-week course of = preemptive=20 ganciclovir treatment should be administered (BIII) (Appen= dix).=20 Ganciclovir should also be started if the patient has had = >2=20 consecutively positive viremia or PCR tests (e.g., in a person = receiving=20 steroids for GVHD or who received ganciclovir or foscarnet at = <100 days=20 after HSCT). Current investigational strategies for preventing = late CMV=20 disease include the use of targeted prophylaxis with antiviral = drugs and=20 cellular immunotherapy for those with deficient or absent = CMV-specific=20 immune system function.

If viremia persists after 4 weeks of ganciclovir preemptive = therapy or=20 if the level of antigenemia continues to rise after 3 weeks of = therapy,=20 ganciclovir-resistant CMV should be suspected. If CMV viremia = recurs=20 during continuous treatment with ganciclovir, researchers report=20 restarting ganciclovir induction (100) or stopping = ganciclovir and=20 starting foscarnet (CIII). Limited data were found regarding the = use of=20 foscarnet among HSCT recipients for either CMV prophylaxis or = preemptive=20 therapy (92,93).

Infusion of donor-derived CMV-specific clones of CD8+ T-cells = into the=20 transplant recipient is being evaluated under FDA Investigational = New Drug=20 authorization; therefore, no recommendation can be made. Although, = in a=20 substantial cooperative study, high-dose acyclovir has had certain = efficacy for preventing CMV disease (101), its utility is = limited=20 in a setting where more potent anti-CMV agents (e.g., ganciclovir) = are=20 used (102). Acyclovir is not effective in preventing CMV = disease=20 after autologous HSCT (103) and is, therefore, not = recommended for=20 CMV preemptive therapy (DII). Consequently, valacyclovir, although = under=20 study for use among HSCT recipients, is presumed to be less = effective than=20 ganciclovir against CMV and is currently not recommended for CMV = disease=20 prevention (DII).

Although HSCT physicians continue to use IVIG for immune system = modulation, IVIG is not recommended for CMV disease prophylaxis = among HSCT=20 recipients (DI). Cidofovir, a nucleoside analog, is approved by = FDA for=20 the treatment of AIDS-associated CMV retinitis. The drug's major=20 disadvantage is nephrotoxicity. Cidofovir is currently in FDA = phase 1=20 trial for use among HSCT recipients; therefore, recommendations = for its=20 use cannot be made.

Use of CMV-negative or leukocyte-reduced blood products is not=20 routinely required for all autologous recipients because most have = a=20 substantially lower risk for CMV disease. However, CMV-negative or = leukocyte-reduced blood products can be used for CMV-seronegative=20 autologous recipients (CIII). Researchers report that = CMV-seropositive=20 autologous recipients be evaluated for preemptive therapy if they = have=20 underlying hematologic malignancies (e.g., lymphoma or leukemia), = are=20 receiving intense conditioning regimens or graft manipulation, or = have=20 recently received fludarabine or 2-chlorodeoxyadenosine (CDA) = (CIII). This=20 subpopulation of autologous recipients should be monitored weekly = from=20 time of engraftment until 60 days after HSCT for CMV reactivation, = preferably with quantitative CMV pp65 antigen (80) or = quantitative=20 PCR (BII).

Autologous recipients at high risk who experience CMV = antigenemia=20 (i.e., blood levels of >5 positive cells/slide) should = receive 3=20 weeks of preemptive treatment with ganciclovir or foscarnet = (80),=20 but CD34+-selected patients should be treated at any level of = antigenemia=20 (BII) (Appen= dix).=20 Prophylactic approach to CMV disease prevention is not appropriate = for=20 CMV-seropositive autologous recipients. Indications for the use of = CMV=20 prophylaxis or preemptive treatment are the same for children or = adults.=20

Recommendations Regarding EBV

Preventing Exposure

All transplant candidates, particularly those who are = EBV-seronegative,=20 should be advised of behaviors that could decrease the likelihood = of EBV=20 exposure (AII). For example, HSCT recipients and candidates should = follow=20 safe hygiene practices (e.g., frequent hand washing [AIII] and = avoiding=20 the sharing of cups, glasses, and eating utensils with others)=20 (104) (BIII), and they should avoid contact with = potentially=20 infected respiratory secretions and saliva (104) (AII). =

Preventing Disease

Infusion of donor-derived, EBV-specific cytotoxic T-lymphocytes = has=20 demonstrated promise in the prophylaxis of EBV-lymphoma among = recipients=20 of T-cell--depleted unrelated or mismatched allogeneic recipients=20 (105,106). However, insufficient data were found to = recommend its=20 use. Prophylaxis or preemptive therapy with acyclovir is not = recommended=20 because of lack of efficacy (107,108) (DII).

Recommendations Regarding HSV

Preventing Exposure

HSCT candidates should be tested for serum anti-HSV IgG before=20 transplant (AIII); however, type-specific anti-HSV IgG serology = testing is=20 not necessary. Only FDA-licensed or -approved tests should be = used. All=20 HSCT candidates, particularly those who are HSV-seronegative, = should be=20 informed of the importance of avoiding HSV infection while=20 immunocompromised and should be advised of behaviors that will = decrease=20 the likelihood of HSV exposure (AII). HSCT recipients and = candidates=20 should avoid sharing cups, glasses, and eating utensils with = others=20 (BIII). Sexually active patients who are not in a long-term = monogamous=20 relationship should always use latex condoms during sexual contact = to=20 reduce the risk for exposure to HSV as well as other sexually = transmitted=20 pathogens (AII). However, even long-time monogamous pairs can be=20 discordant for HSV infections. Therefore, during periods of=20 immunocompromise, sexually active HSCT recipients in such = relationships=20 should ask partners to be tested for serum HSV IgG antibody. If = the=20 partners are discordant, they should consider using latex condoms = during=20 sexual contact to reduce the risk for exposure to this sexually=20 transmitted OI (CIII). Any person with disseminated, primary, or = severe=20 mucocutaneous HSV disease should be placed under contact = precautions for=20 the duration of the illness (62) (AI) to prevent = transmission of=20 HSV to HSCT recipients.

Preventing Disease and Disease Recurrence

Acyclovir. Acyclovir prophylaxis should be = offered to all=20 HSV-seropositive allogeneic recipients to prevent HSV reactivation = during=20 the early posttransplant period (109--113) (AI). Standard = approach=20 is to begin acyclovir prophylaxis at the start of the conditioning = therapy=20 and continue until engraftment occurs or until mucositis resolves, = whichever is longer, or approximately 30 days after HSCT (BIII) = (Appen= dix).=20 Without supportive data from controlled studies, routine use of = antiviral=20 prophylaxis for >30 days after HSCT to prevent HSV is not = recommended=20 (DIII). Routine acyclovir prophylaxis is not indicated for=20 HSV-seronegative HSCT recipients, even if the donors are = HSV-seropositive=20 (DIII). Researchers have proposed administration of ganciclovir=20 prophylaxis alone (86) to HSCT recipients who required = simultaneous=20 prophylaxis for CMV and HSV after HSCT (CIII) because ganciclovir = has in=20 vitro activity against CMV and HSV 1 and 2 (114), although=20 ganciclovir has not been approved for use against HSV.

Valacyclovir. Researchers have reported = valacyclovir use=20 for preventing HSV among HSCT recipients (CIII); however, = preliminary data=20 demonstrate that very high doses of valacyclovir (8 g/day) were = associated=20 with thrombotic thrombocytopenic purpura/hemolytic uremic syndrome = among=20 HSCT recipients (115). Controlled trial data among HSCT = recipients=20 are limited (115), and the FDA has not approved = valacyclovir for=20 use among recipients. Physicians wishing to use valacyclovir among = recipients with renal impairment should exercise caution and = decrease=20 doses as needed (BIII) (Appen= dix).=20

Foscarnet. Because of its substantial renal and=20 infusion-related toxicity, foscarnet is not recommended for = routine HSV=20 prophylaxis among HSCT recipients (DIII).

Famciclovir. Presently, data regarding safety and = efficacy of famciclovir among HSCT recipients are limited; = therefore, no=20 recommendations for HSV prophylaxis with famciclovir can be made. =

Other Recommendations

HSV prophylaxis lasting >30 days after HSCT might be = considered for=20 persons with frequent recurrent HSV (CIII) (Appen= dix).=20 Acyclovir can be used during phase I for administration to=20 HSV-seropositive autologous recipients who are likely to = experience=20 substantial mucositis from the conditioning regimen (CIII). = Antiviral=20 prophylaxis doses should be modified for use among children (Appen= dix),=20 but no published data were found regarding valacyclovir safety and = efficacy among children.

Recommendations Regarding VZV

Preventing Exposure

HSCT candidates should be tested for the presence of serum = anti-VZV IgG=20 antibodies (AIII). However, these tests are not 100% reliable,=20 particularly among severely immunosuppressed patients. Researchers = recommend that a past history of varicella accompanied by a = positive titer=20 is more likely to indicate the presence of immunity to VZV than a = low=20 positive titer alone. All HSCT candidates and recipients, = particularly=20 those who are VZV-seronegative, should be informed of the = potential=20 seriousness of VZV disease among immunocompromised persons and = advised of=20 strategies to decrease their risk for VZV exposure = (116--122)=20 (AII).

Although researchers report that the majority of VZV disease = after HSCT=20 is caused by reactivation of endogenous VZV, HSCT candidates and=20 recipients who are VZV-seronegative, or VZV-seropositive and=20 immunocompromised, should avoid exposure to persons with active = VZV=20 infections (123) (AII). HCWs, family members, household = contacts,=20 and visitors who are healthy and do not have a reported history of = varicella infection or who are VZV-seronegative should receive VZV = vaccination before being allowed to visit or have direct contact = with an=20 HSCT recipient (AIII). Ideally, VZV-susceptible family members, = household=20 contacts, and potential visitors of immunocompromised HSCT = recipients=20 should be vaccinated as soon as the decision is made to perform = HSCT. The=20 vaccination dose or doses should be completed >4 weeks = before=20 the conditioning regimen begins or >6 weeks (42 days) = before the=20 HSCT is performed (BIII).

HSCT recipients and candidates undergoing conditioning therapy = should=20 avoid contact with any VZV vaccine recipient who experiences a = rash after=20 vaccination (BIII). When this rash occurs, it usually appears = 14--21 days=20 after VZV vaccination (median: 22 days; range: 5--35 days) = (personal=20 communication from Robert G. Sharrar, M.D., Merck & Co., = Inc.).=20 However, to date, no serious disease has been reported among=20 immuno-compromised patients from transmission of VZV vaccine = virus, and=20 the VZV vaccine strain is susceptible to acyclovir.

All HSCT recipients with VZV disease should be placed under = airborne=20 and contact precautions (62) (AII) to prevent transmission = to other=20 HSCT recipients. Contact precautions should be continued until all = skin=20 lesions are crusted. Airborne precautions should be instituted 10 = days=20 after exposure to VZV and continued until 21 days after last = exposure or=20 28 days postexposure if the patient received varicella-zoster=20 immunoglobulin (VZIG)**** (62) (AI) because a person = infected with=20 VZV can be infectious before the rash appears.

Preventing Disease

VZIG. VZV-seronegative HSCT recipients should be=20 administered VZIG as soon as possible but ideally within 96 hours = after=20 close or household contact with a person having either chickenpox = or=20 shingles if the HSCT recipient is not immunocompetent (i.e., = allogeneic=20 patient <24 months after HSCT, >24 months after HSCT = and on=20 immunosuppressive therapy, or having chronic GVHD) (AII). = Researchers=20 report VZIG administration for VZV exposure as described for HSCT=20 recipients who were VZV-seropositive before HSCT (CIII).

Because of the high morbidity of VZV-associated disease among = severely=20 immunocompromised HSCT recipients and until further data are = published,=20 HSCT physicians should administer VZIG to all VZV-seronegative = HSCT=20 recipients or candidates undergoing conditioning therapy who are = exposed=20 to a VZV vaccinee having a varicella-like rash (BIII). Researchers = also=20 report VZIG administration for this situation for VZV-seropositive = HSCT=20 recipients and candidates undergoing conditioning therapy (CIII). = These=20 recommendations are made because the vaccinee might be unknowingly = incubating wild-type varicella, particularly during the first 14 = days=20 after varicella vaccination, and because vaccine-strain VZV has = been=20 rarely transmitted by VZV vaccinees with vesicular rashes = postvaccination=20 (121).

If VZV-seronegative HSCT recipients or candidates undergoing=20 conditioning therapy are closely exposed to varicella >3 weeks = after=20 receiving VZIG, they should be administered another dose of VZIG=20 (120) (BIII). Researchers also recommend VZIG = administration for=20 this condition for VZV-seropositive HSCT recipients and candidates = undergoing conditioning therapy (CIII).

Antiviral Drugs. Any HSCT recipient or candidate=20 undergoing conditioning therapy who experiences a VZV-like rash=20 (particularly after exposure to a person with wild-type varicella = or=20 shingles) should receive preemptive intravenous acyclovir until=20 >2 days after all lesions have crusted (BIII) (Appen= dix).=20 Any HSCT recipient or candidate undergoing conditioning therapy = who=20 experiences a VZV-like rash after exposure to a VZV vaccinee with = a rash=20 should be administered intravenous acyclovir preemptively to = prevent=20 severe, disseminated VZV disease (BII). Acyclovir should be = administered=20 until 2 days after all lesions have crusted.

Long-term acyclovir prophylaxis to prevent recurrent VZV = infection=20 (e.g., during the first 6 months after HSCT) is not routinely = recommended=20 (124--126) (DIII); however, this therapy could be = considered for=20 use among HSCT recipients with severe, long-term immunodeficiency = (CIII).=20 When acyclovir resistance occurs among patients, HSCT physicians = should=20 use foscarnet for preemptive treatment of VZV disease (127) = (BIII).=20 Researchers report valacyclovir use for preventing HSV among HSCT=20 recipients (CIII). However, preliminary data demonstrate that very = high=20 doses of valacyclovir (8 g/day) were associated with thrombotic=20 thrombocytopenic purpura/hemolytic uremic syndrome among HSCT = recipients=20 (115). Controlled trial data regarding HSCT recipients are = limited=20 (115), and the FDA has not approved valacyclovir for use = among HSCT=20 recipients. Physicians wishing to use valacyclovir among HSCT = recipients=20 with renal impairment should exercise caution and decrease doses = as needed=20 (BIII) (Appen= dix).=20 No data were found demonstrating safety and efficacy of preemptive = treatment of famciclovir against herpes zoster among HSCT = recipients.=20 Consequently, no recommendation for its use can be made.

Live-Attenuated VZV Vaccine. VZV vaccine use is=20 contraindicated among HSCT recipients <24 months after HSCT=20 (128) (EIII). Use of VZV vaccine among HSCT recipients is=20 restricted to research protocols for recipients >24 = months after=20 HSCT who are presumed immunocompetent. Further research is needed = to=20 determine the safety, immunogenicity, and efficacy of VZV vaccine = among=20 HSCT recipients.

Other Recommendations

An inactivated VZV vaccine has been used investigationally = among HSCT=20 recipients (129); however, more studies are needed before a = recommendation regarding its use can be made. Recommendations for = VZV=20 prevention are the same for allogeneic or autologous recipients.=20 Recommendations for preventing VZV disease among pediatric or = adult HSCT=20 recipients are the same, except that appropriate dose adjustments = for VZIG=20 should be made for pediatric HSCT recipients (AIII) (Appen= dix).=20

Recommendations Regarding CRV Infections: Influenza, = Respiratory=20 Syncytial Virus, Parainfluenza Virus, and Adenovirus

Preventing Exposure

Preventing CRV exposure is critical in preventing CRV disease=20 (130,131). To prevent nosocomial CRV transmission, HSCT = recipients=20 and their HCWs should always follow HSCT infection control = guidelines=20 (AIII). To minimize the risk for CRV transmission, HCWs and = visitors with=20 upper respiratory infection (URI) symptoms should be restricted = from=20 contact with HSCT recipients and HSCT candidates undergoing = conditioning=20 therapy (AIII). At a minimum, active clinical surveillance for CRV = disease=20 should be conducted on all hospitalized HSCT recipients and = candidates=20 undergoing conditioning therapy; this clinical surveillance should = include=20 daily screening for signs and symptoms of CRV (e.g., URI or lower=20 respiratory infection [LRI]) (AIII). Viral cultures of = asymptomatic HSCT=20 candidates are unlikely to be useful. HSCT recipients with URI or = LRI=20 symptoms should be placed under contact precautions to avoid = transmitting=20 infection to other HSCT candi dates and recipients, HCWs, and = visitors=20 until the etiology of illness is identified (62) (BIII). = Optimal=20 isolation precautions should be modified as needed after the = etiology is=20 identified (AIII). HSCT recipients and candidates, their family = members=20 and visitors, and all HCWs should be informed regarding CRV = infection=20 control measures and the potential severity of CRV infections = among HSCT=20 recipients (130--140) (BIII). Physicians have routinely = conducted=20 culture-based CRV surveillance among HSCT recipients; however, the = cost=20 effectiveness of this approach has not been evaluated.

Influenza vaccination of family members and close or household = contacts=20 is strongly recommended during each influenza season (i.e., = October--May)=20 starting the season before HSCT and continuing >24 = months after=20 HSCT (141) (AI) to prevent influenza exposure among the = recipients=20 or candidates. All family members and close or household contacts = of HSCT=20 recipients who remain immunocompromised >24 months after = HSCT=20 should continue to be vaccinated annually as long as the HSCT = recipient's=20 immuno-compromise persists (141) (AI). Seasonal influenza=20 vaccination is strongly recommended for all HCWs of HSCT = recipients=20 (142,143) (AI).

If HCWs, family members, or other close contacts of HSCT = recipients=20 receive influenza vaccination during an influenza A outbreak, they = should=20 receive amantadine or rimantadine chemoprophylaxis for 2 weeks = after=20 influenza vaccination (BI) while the vaccinee experiences an = immunologic=20 response to the vaccine. Such a strategy is likely to prevent = transmission=20 of influenza A to HCWs and other close contacts of HSCT = recipients, which=20 could prevent influenza A transmission to HSCT recipients = themselves.=20 However, if a nosocomial outbreak occurs with an influenza A = strain that=20 is not contained in the available influenza vaccine, all healthy = family=20 members, close and household contacts, and HCWs of HSCT recipients = and=20 candidates should be administered influenza A chemoprophylaxis = with=20 amantadine or rimantadine until the end of the outbreak = (141)=20 (BIII).

In 1999, two neuroaminidase inhibitors (zanamivir and = oseltamivir) were=20 approved for treatment of influenza, but are not currently = approved for=20 prophylaxis. To date, experience is limited regarding use of = zanamivir or=20 oseltamivir in the treatment or prophylaxis of influenza among = HSCT=20 settings. However, HCWs, family members, or other close contacts = can be=20 offered a neuroaminidase inhibitor (e.g., zanamivir or = oseltamivir) using=20 the same strategies outlined previously, if a) rimantadine or = amantadine=20 cannot be tolerated, b) the outbreak strain of influenza A is = amantadine=20 or rimantadine-resistant, or c) the outbreak strain is influenza B = (144--147) (BI). Zanamivir can be administered to persons = aged=20 >12 years, and oseltamivir can be administered to = persons aged=20 >18 years. Patients with influenza should be placed = under=20 droplet and standard precautions (AIII) to prevent transmission of = influenza to HSCT recipients. HCWs with influenza should be = excused from=20 patient care until they are no longer infectious (AIII).

Preventing Disease

HSCT physicians should determine the etiology of a URI in an = HSCT=20 recipient or candidate undergoing conditioning therapy, if = possible,=20 because respiratory syncytial virus (RSV), influenza, = parainfluenza, and=20 adenovirus URIs can progress to more serious LRI, and certain CRVs = can be=20 treated (BIII). Appropriate diagnostic samples include = nasopharyngeal=20 washes, swabs or aspirates, throat swabs, and bronchoalveolar = lavage (BAL)=20 fluid. HSCT candidates with URI symptoms at the time conditioning = therapy=20 is scheduled to start should postpone their conditioning regimen = until the=20 URIs resolve, if possible, because certain URIs might progress to = LRI=20 during immunosuppression (131,133,137,138) (BIII).

Recommendations Regarding Influenza. Life-long = seasonal=20 influenza vaccination is recommended for all HSCT candidates and=20 recipients, beginning during the influenza season before HSCT and = resuming=20 >6 months after HSCT (142) (BIII). Influenza = vaccinations=20 administered to HSCT recipients <6 months after HSCT are = unlikely to be=20 beneficial and are not recommended (142) (DII). HSCT = recipients=20 <6 months after HSCT should receive chemoprophylaxis with = amantadine or=20 rimantadine during community or nosocomial influenza A outbreaks = (BIII).=20 These drugs are not effective against influenza B. Additionally,=20 antiviral-resistant strains of influenza can emerge during = treatment with=20 amantadine or rimantadine and transmission of resistant strains = can occur=20 (148,149). During such outbreaks, HSCT recipients 6--24 = months=20 after HSCT, or >24 months after HSCT and still substantially=20 immunocompromised (i.e., receiving immunosuppressive therapy, have = had a=20 relapse of their underlying disease, or have GVHD) and who have = not yet=20 received a current influenza vaccination, should be vaccinated = against=20 influenza immediately (BIII). Additionally, to allow sufficient = time for=20 the patient to experience an immunologic response to influenza = vaccine,=20 chemoprophylaxis with amantadine or rimantadine can be used for = these HSCT=20 recipients for 2 weeks after vaccination during a nosocomial or = community=20 influenza A outbreak (CIII). Influenza A chemoprophylaxis with = amantadine=20 or rimantadine has been recommended for all influenza A-exposed = HSCT=20 recipients <24 months after HSCT or >24 months after = HSCT and=20 substantially immunocompromised regardless of vaccination history, = because=20 of their likely suboptimal immunologic response to influenza = vaccine=20 (142,143). However, no recommendation regarding such=20 chemoprophylaxis can be made because of lack of data.

To prevent severe disease, early preemptive therapy with = amantadine or=20 rimantadine has been reported for HSCT recipients with unexplained = acute=20 URI or LRI symptoms during a community or nosocomial outbreak of = influenza=20 A (141). However, the effectiveness in preventing = influenza-related=20 complications and the safety of this strategy have not been = evaluated=20 among HSCT recipients. Therefore, data are insufficient to make a=20 recommendation.

Neuroaminidase inhibitors (zanimivir and oseltamivir), = intravenous and=20 aerosol ribavirin, and combination drug therapy (e.g., rimantadine = or=20 amantadine with ribavirin or interferon) (143,150--153) = have been=20 proposed for investigational, preemptive treatment to prevent = severe=20 influenza disease among HSCT recipients. However, because of lack = of data,=20 no recommendation for use of these strategies among HSCT = recipients can be=20 made.

Recommendations Regarding RSV. Respiratory = secretions of=20 any hospitalized HSCT candidate or recipient who experiences signs = or symptoms of CRV infection should be tested promptly by = viral=20 culture and rapid diagnostic tests for RSV (BIII). If two = diagnostic=20 samples taken >2 days apart do not identify a = respiratory=20 pathogen despite persistence of respiratory symptoms, BAL and = further=20 testing are advised (BIII). This testing is critical because of = the high=20 morbidity and case fatality of RSV disease among HSCT recipients=20 (154,155). HSCT recipients, particularly those who are=20 preengraftment and at highest risk for severe RSV pneumonia, = should have=20 their illness diagnosed early (i.e., during RSV URI), and their = illness=20 should be treated aggressively to prevent fatal RSV disease = (BIII).

Although a definitive, uniformly effective preemptive therapy = for RSV=20 infection among HSCT recipients has not been identified, certain=20 strategies have been proposed, including use of aerosolized = ribavirin=20 (155,156), RSV antibodies (i.e., passive immunization with = high=20 RSV-titered IVIG or RSV immunoglobulin) in combination with = aerosolized=20 ribavirin (137,157), and RSV monoclonal antibody = (158).=20 Clinical trials are currently underway to evaluate the efficacy of = these=20 strategies. No recommendation regarding the optimal method for RSV = prevention and preemptive therapy can be made because of limited = data.=20 Further, current data do not support use of intravenous ribavirin = for=20 preemptive therapy for RSV pneumonia among HSCT recipients = (60)=20 (DIII), and no commercially licensed vaccines against RSV are = currently=20 available.

Recommendations Regarding Parainfluenza Virus and=20 Adenovirus. Immuno-prophylaxis, chemoprophylaxis, and = preemptive=20 treatment for parainfluenza virus and adenovirus infections among = HSCT=20 recipients have been proposed (159,160). However, no = recommendation=20 can be made in these guidelines because of insufficient data. No=20 commercially licensed vaccines against parainfluenza or adenovirus = are=20 currently available.

Other Disease Prevention Recommendations

The recommendations for preventing CRV infections and their = recurrence=20 are the same for allogeneic or autologous recipients. Generally, = these=20 recommendations apply to children or adults (161--164), but = with=20 appropriate adjustments in antiviral drug and influenza vaccine = doses for=20 children (Appen= dix).=20

For pediatric HSCT recipients and candidates aged >6 months, = annual=20 seasonal influenza vaccination is recommended HSCT (BIII). = Children aged=20 <9 years who are receiving influenza vaccination for the first = time=20 require two doses administered >1 months apart (AI). = Healthy=20 children who receive influenza vaccination for the first time = might not=20 generate protective antibodies until 2 weeks after receipt of the = second=20 dose of influenza vaccine. Therefore, during an influenza A = outbreak,=20 pediatric recipients aged <9 years, >6 months after = HSCT, and=20 receiving their first influenza vaccination, should be = administered=20 >6 weeks of influenza A chemoprophylaxis after the first = dose of=20 influenza vaccine (141) (BIII) (Appen= dix).=20 Amantadine and rimantadine are not FDA-approved for children aged = <1=20 year (141,161) (DIII).

To prevent RSV disease, researchers report substituting = RSV-IVIG for=20 IVIG during RSV season (i.e., November--April) for pediatric = recipients=20 (i.e., children aged <18 years) who receive routine IVIG = therapy=20 (164) (i.e., those with hypogammaglobulinemia) (CIII) (Appen= dix).=20 Other researchers report that pediatric recipients with RSV can be = considered for preemptive therapy (e.g., during URI or early LRI) = with=20 aerosolized ribavirin (CIII), although this therapy remains = controversial=20 (164) (Appen= dix).=20 Droplet and contact precautions for the duration of illness are = required=20 for pediatric recipients for the duration of adenovirus = (62)=20 (AIII).=20
FUNGAL INFECTIONS

General Recommendations

Preventing Exposure

Limited data were found that demonstrate to what extent = preventing=20 fungal exposures is effective in preventing infection and disease. = However, HSCT recipients and candidates undergoing conditioning = therapy=20 have been advised to avoid contact with certain areas and = substances,=20 including foods, that might increase a patient's risk for fungal = exposures=20 (CII). Specific precautions have included avoiding areas of high = dust=20 exposure (e.g., excavation sites, areas of building construction = or=20 renovation, chicken coops, and caves), occupations involving soil, = and=20 foods that contain molds (e.g., blue cheese).

Preventing Disease

Growth factors (e.g., GM-CSF and G-CSF) shorten the duration of = neutropenia after HSCT (165); however, no data were found = that=20 indicate which growth factors effectively reduce the attack rate = of=20 invasive fungal disease. Therefore, no recommendation for use of = growth=20 factors solely for prophylaxis against invasive fungal disease can = be=20 made.

Topical antifungal drugs, which are applied to the skin or = mucosa=20 (e.g., nystatin or clotrimazole), might reduce fungal colonization = in the=20 area of application. However, these agents have not been proven to = prevent=20 generation of locally invasive or disseminated yeast infections = (e.g.,=20 candidiasis) or mold infections (e.g., aspergillosis) and are not=20 recommended for their prophylaxis (DII). Performing fungal = surveillance=20 cultures is not indicated for asymptomatic HSCT recipients=20 (166,167) (DII), but cultures should be obtained from = symptomatic=20 HSCT recipients (BIII).

Recommendations Regarding Yeast Infections

Preventing Exposure

Invasive candidiasis is usually caused by dissemination of = endogenous=20 Candida species that have colonized a patient's = gastrointestinal=20 tract (168). Consequently, methods of preventing exogenous = yeast=20 exposure usually do not prevent invasive yeast infections after = HSCT.=20 However, because Candida species can be carried on the = hands, HCWs=20 and others in contact with HSCT recipients should follow = appropriate=20 hand-washing practices to safeguard patients from exposure (AIII). =

Preventing Disease

Allogeneic recipients should be administered fluconazole = prophylaxis to=20 prevent invasive disease with fluconazole-susceptible = Candida=20 species during neutropenia, particularly among centers where = Can.=20 albicans is the predominant cause of invasive fungal disease=20 preengraftment (AI) (Appen= dix).=20 Because candidiasis occurs during phase I (169), = fluconazole (400=20 mg/day by mouth or intravenously) should be administered = (169,170)=20 from the day of HSCT until engraftment (AII). However, fluconazole = is not=20 effective against certain Candida species, including = Can.=20 krusei (171) and Can. glabrata and is, = therefore, not=20 recommended for their prevention (DI). Further studies are needed = to=20 determine the optimal duration of fluconazole prophylaxis. = Preliminary=20 studies have reported that low-dose fluconazole prophylaxis = (100--200=20 mg/day by mouth) among neutropenic patients has variable efficacy = in=20 preventing candidiasis (172). Therefore, this therapy is = not=20 recommended for HSCT recipients (DII). Oral, nonabsorbable = antifungal=20 drugs, including oral amphotericin B (500 mg suspension every 6 = hours),=20 nystatin, and clotrimazole troches, might reduce superficial = colonization=20 and control local mucosal candidiasis, but have not been = demonstrated to=20 reduce invasive candidiasis (CIII).

Other Recommendations

HSCT candidates with candidemia or invasive candidiasis can = safely=20 receive transplants (173) if a) their infection was = diagnosed early=20 and treated immediately and aggressively with amphotericin B or=20 alternatively with appropriate doses of fluconazole if the = organism is=20 susceptible; and b) evidence of disease control is reported (e.g., = by=20 serial computed tomography scans) before the transplant (BIII). = Such=20 patients should continue receiving therapeutic doses of an = appropriate=20 antifungal drug throughout phase I (BII) and until a careful = review of=20 clinical, laboratory, and serial computed tomography scans = verifies=20 resolution of candidiasis (BII).

Because autologous recipients generally have an overall lower = risk for=20 invasive fungal infection than allogeneic recipients, certain = autologous=20 recipients do not require routine antiyeast prophylaxis (DIII). = However,=20 researchers recommend administering antiyeast prophylaxis to a=20 subpopulation of autologous recipients with underlying hematologic = malignancies (e.g., lymphoma or leukemia) and who have or will = have=20 prolonged neutropenia and mucosal damage from intense conditioning = regimens or graft manipulation, or have received fludarabine or = 2-CDA=20 recently (BIII). Recommendations regarding preventing invasive = yeast=20 infections among pediatric or adult HSCT recipients are the same, = except=20 that appropriate dose adjustments for prophylactic drugs should be = made=20 for pediatric recipients (Appen= dix).=20

Recommendations Regarding Mold Infections

Preventing Exposure

Nosocomial mold infections among HSCT recipients result = primarily from=20 respiratory exposure to and direct contact with fungal spores=20 (174). Ongoing hospital construction and renovation have = been=20 associated with an increased risk for nosocomial mold infection,=20 particularly aspergillosis, among severely immunocompromised = patients=20 (175--177). Therefore, whenever possible, HSCT recipients = who=20 remain immunocompromised should avoid hospital construction or = renovation=20 areas (AIII). When constructing new HSCT centers or renovating old = ones,=20 hospital planners should ensure that rooms for HSCT patients have = an=20 adequate capacity to minimize fungal spore counts through use of=20

high-efficiency (>90%) particulate air (HEPA) filtration=20 (140,178,179) (BIII);=20
directed room airflow (i.e., positive air pressure in = patient rooms=20 in relation to corridor air pressure) so that air from patient = rooms=20 flows into the corridor (180) (BIII);=20
correctly sealed rooms, including correctly sealed windows = and=20 electrical outlets (140) (BIII);=20
high rates of room air exchange (i.e., >12 air = changes/hour)=20 (140,178) (BIII); and=20
barriers between patient care and renovation or construction = areas=20 (e.g., sealed plastic) that prevent dust from entering patient = care=20 areas and that are=20
impermeable to Aspergillus species (175,179) = (BIII).=20
Additionally, HSCT centers should be cleaned with = care,=20 particularly after hospital renovation or construction, to avoid = exposing=20 HSCT recipients and candidates to mold spores (174,176) = (BIII).=20
Preventing Disease

No regimen has been reported to be clearly effective or = superior in=20 preventing aspergillosis, and therefore, no recommendation can be = made.=20 Further studies are needed to determine the optimal strategy for=20 aspergillosis prevention. Moderate-dose (0.5 mg/kg/day) = amphotericin B=20 (181--184), low-dose (0.1--0.25 mg/kg/day) amphotericin B=20 (185--187), intranasal amphotericin B spray (188), = lipid=20 formulations of amphotericin B (182,189), and aerosolized=20 amphotericin B (190) have been administered for = aspergillosis=20 prophylaxis, but data are limited regarding the safety and = efficacy of=20 these formulations among HSCT recipients. Additionally, = itraconazole=20 capsules are not recommended for fungal prophylaxis among HSCT = recipients=20 (191) (DII) for three reasons. First, itraconazole capsules = are=20 poorly absorbed gastrointestinally, particularly among patients = who are=20 fasting (192) or receiving cytotoxic agents (193). = Second,=20 persons taking itraconazole capsules do not achieve steady-state = serum=20 levels for 2 weeks (188,194), and when achieved, these = levels are=20 lower than the average Aspergillus species minimum = inhibitory=20 concentration (MIC) among HSCT recipients (195). Third,=20 itraconazole has adverse interactions with other drugs (e.g.,=20 antiepileptics, rifampin, oral hypoglycemics, protease inhibitors, = vinca=20 alkaloids, cyclosporine, methylprednisolone, and warfarin-like=20 anticoagulants) (196). Trials assessing the efficacy of the = recently licensed cyclodextrin oral solution and intravenous = formulations=20 of itraconazole in preventing invasive fungal disease among HSCT=20 recipients are in progress; however, no recommendations regarding = its use=20 for Aspergillus species infection prophylaxis can be made. = For HSCT=20 recipients whose respiratory specimens are culture positive for=20 Aspergillus species, acute invasive aspergillosis should be = diagnosed presumptively (197) and treated preemptively and=20 aggressively (e.g., with intravenous amphotericin) (AIII).

The risk for aspergillosis recurrence has been high among = allogeneic=20 recipients with preexisting invasive aspergillosis. Previously, = allogeneic=20 HSCTs were avoided among persons with uncontrolled, proven = aspergillosis.=20 However, HSCT center personnel have recently reported successful=20 allogeneic or autologous HSCT among a limited number of persons = who have=20 had successfully treated, prior invasive pulmonary aspergillosis=20 (198--200). Because of limited data, no recommendations = regarding=20 strategies for preventing aspergillosis recurrence can be made.=20
PROTOZOAL AND HELMINTHIC INFECTIONS

Recommendations Regarding PCP

Preventing Exposure

Although a possible cause of PCP is reactivation of latent = infection=20 among immunocompromised persons, cases of person-to-person = transmission of=20 PCP have been reported (201--206). Generally, standard = precautions=20 should be used for patients with PCP (62) (BIII), but = researchers=20 have reported patients with PCP being isolated (201,204) = and=20 contact precautions being used if evidence existed of = person-to-person=20 transmission in the institution (CIII). This subject remains=20 controversial, and until further data are published, HSCT = recipients=20 should avoid exposure to persons with PCP (62) (CIII).

Preventing Disease and Disease Recurrence

Physicians should prescribe PCP prophylaxis for allogeneic = recipients=20 throughout all periods of immunocompromise (207) after = engraftment.=20 Prophylaxis should be administered from engraftment until 6 months = after=20 HSCT (AII) for all patients, and >6 months after HSCT for the = duration=20 of immunosuppression for those who a) are receiving = immunosuppressive=20 therapy (e.g. prednisone or cyclosporine) (AI), or b) have chronic = GVHD=20 (BII). However, PCP prophylaxis can be initiated before = engraftment if=20 engraftment is delayed (CIII). Researchers report an additional 1- = to=20 2-week course of PCP prophylaxis before HSCT (i.e., day --14 to = day --2)=20 (CIII).

Preferred PCP prophylaxis is TMP-SMZ (AII); however, if TMP-SMZ = is=20 administered before engraftment, the associated myelosuppression = could=20 delay engraftment, and patients might experience sensitivity to = the drug.=20 Every effort should be made to keep such patients on the drug, = including=20 assessment of desensitization therapy, although data regarding = this=20 technique among HSCT recipients are limited. For patients who = cannot=20 tolerate TMP-SMZ, physicians can choose to use alternative PCP = prophylaxis=20 regimens (e.g., dapsone) (208) (BIII). Use of aerosolized=20 pentamidine (209) is associated with the lowest PCP = prevention=20 rates and should only be used if other agents cannot be tolerated. = Atovaquone is a possible alternative drug for PCP prophylaxis = among=20 dapsone-intolerant persons with HIV infection (210); = however, no=20 recommendation regarding use of atovaquone among HSCT recipients = can be=20 made because of lack of data. Although data are limited, = concomitant use=20 of leucovorin (folinic acid) and TMP-SMZ is not recommended=20 (211,212) (DIII). A patient's history of PCP should not be = regarded=20 as a contraindication to HSCT (213) (DIII).

Recurrent PCP among HSCT recipients is rare; however, patients = with=20 continued immunosuppression should remain on PCP prophylaxis until = their=20 immunosuppression is resolved (AI). The regimen recommended for = preventing=20 toxoplasmosis recurrence among HSCT recipients (i.e., TMP-SMZ) = will also=20 prevent PCP recurrence.

Other Recommendations

PCP prophylaxis should be considered for autologous recipients = who have=20 underlying hematologic malignancies (i.e., lymphoma or leukemia), = are=20 receiving intense conditioning regimens or graft manipulation, or = have=20 recently received fludarabine or 2-CDA (207,214) (BIII). = PCP=20 prophylaxis should be administered >6 months after HSCT = if=20 substantial immunosuppression or immunosuppressive therapy (e.g.,=20 steroids) persists (CIII). Use of PCP prophylaxis among other = autologous=20 recipients is controversial (CIII). Generally, indications for PCP = prophylaxis are the same among children or adults, but pediatric = doses=20 should be used (Appen= dix).=20

Recommendations Regarding Toxoplasma gondii =

Preventing Exposure

All HSCT recipients should be provided information regarding = strategies=20 to reduce their risk for Toxoplasma species exposure. = Researchers=20 report that potential donors for allogeneic HSCT be tested for = To.=20 gondii antibodies (215,216) by using FDA-licensed or = -approved=20 screening tests that include IgG antibody testing because To.=20 gondii has been reported to be transmitted by leukocyte = transfusion=20 (217) and HSCT (218,219) (CIII).

Preventing Disease and Disease Recurrence

Because most toxoplasmosis among HSCT recipients is caused by = disease=20 reactivation, researchers report that candidates for allogeneic = HSCT can=20 be tested for IgG antibody to determine whether they are at risk = for=20 disease reactivation after HSCT (215,216,218) (CIII). = However, the=20 value of such testing is controversial because a limited number of = patients who were seronegative for To. gondii pretransplant = experienced the infection posttransplant (220). If testing = is=20 performed, only FDA-licensed or -approved screening tests should = be used.=20

Researchers recommend toxoplasmosis prophylaxis for = seropositive=20 allogeneic recipients with active GVHD or a prior history of = toxoplasmic=20 chorioretinitis (221,222), but data demonstrating efficacy = are=20 limited (CIII). The optimal prophylactic regimen for toxoplasmosis = among=20 HSCT recipients has not been determined, but a proposed drug is = TMP-SMZ=20 (BII), although allogeneic recipients have experienced = break-through=20 clinical disease despite TMP-SMZ prophylaxis (218). For = patients=20 who are TMP-SMZ--intolerant, a combination of clindamycin, = pyramethamine,=20 and leucovorin can be substituted for To. gondii = prophylaxis (Appen= dix).=20 After therapy for toxoplasmosis, HSCT recipients should continue = receiving=20 suppressive doses of TMP-SMZ or an alternate regimen for the = duration of=20 their immunosuppression (BIII) (Appen= dix).=20

Other Recommendations

Recipients of autologous transplants are at negligible risk for = toxoplasmosis reactivation (218). No prophylaxis or = screening for=20 toxoplasmosis infection is recommended for such patients (DIII).=20 Indications for toxoplasmosis prophylaxis are the same among = children or=20 adults, but pediatric doses should be used among children (Appen= dix).=20

Recommendations Regarding Strongyloides = stercoralis=20

Preventing Exposure

Allogeneic recipients should avoid contact with outhouses and = cutaneous=20 exposure to soil or other surfaces that might be contaminated with = human=20 feces (223) (AIII). Allogeneic recipients who work in = settings=20 (e.g., hospitals or institutions) where they could be exposed to = fecal=20 matter should wear gloves when working with patients or in areas = with=20 potential fecal contamination (AIII).

Preventing Disease and Disease Recurrence

Travel and residence histories should be obtained for all = patients=20 before HSCT to determine any exposures to high-risk areas (e.g., = such=20 moist temperate areas as the tropics, subtropics, or the = southeastern=20 United States and Europe) (223) (BIII). HSCT candidates who = have=20 unexplained peripheral eosinophilia or who have resided in or = traveled to=20 areas endemic for strongyloidiasis, even during the distant past, = should=20 be screened for asymptomatic strongyloidiasis before HSCT (BIII).=20 Serologic testing with an enzyme-linked immunosorbent assay is the = preferred screening method and has a sensitivity and specificity = of=20 >90% (223,224) (BIII). FDA-licensed or -approved = screening tests=20 should be used. Although stool examinations for strongyloidiasis = are=20 specific, the sensitivity obtained from >3 stool = examinations is=20 60%--70%; the sensitivity obtained from concentrated stool exams = is, at=20 best, 80% (223). A total of >3 stool examinations = should=20 be performed if serologic tests are unavailable or if = strongyloidiasis is=20 clinically suspected in a seronegative patient (BIII).

HSCT candidates whose screening tests before HSCT are positive = for=20 Strongyloides species, and those with an unexplained = eosinophilia=20 and a travel or residence history indicative of exposure to=20 Strongyloides stercoralis should be empirically treated = before=20 transplantation (225,226), preferably with ivermectin = (BIII), even=20 if seronegative or stool-negative (Appen= dix).=20

To prevent recurrence among HSCT candidates with = parasitologically=20 confirmed strongyloidiasis, cure after therapy should be verified = with=20 >3 consecutive negative stool examinations before = proceeding=20 with HSCT (AIII). Data are insufficient to recommend a drug = prophylaxis=20 regimen after HSCT to prevent recurrence of strongyloidiasis. HSCT = recipients who had strongyloidiasis before or after HSCT should be = monitored carefully for signs and symptoms of recurrent infection = for 6=20 months after treatment (BIII).

Other Recommendations

Hyperinfection strongyloidiasis has not been reported after = autologous=20 HSCT; however, the same screening precautions should be used among = autologous recipients (BIII). Indications for empiric treatment = for=20 strongyloidiasis before HSCT are the same among children or adults = except=20 for children weighing <15 kg, for whom the preferred drug is=20 thiabendazole (BIII) (Appen= dix).=20

Recommendations Regarding Trypanosoma cruzi =

Preventing Exposure

HSCT physicians should be aware that Trypanosoma cruzi, = the=20 etiologic agent of Chagas' disease, can be transmitted = congenitally,=20 through blood transfusion (227), and possibly through HSCT. = Additionally, treatment for persons infected with Tr. cruzi = is not=20 always effective, even during the acute stage of infection = (227).=20 Therefore, potential donors who were born, received a blood = transfusion,=20 or ever lived for >6 months in a Chagas' disease endemic = area=20 (e.g., parts of South and Central America and Mexico) should be = screened=20 serologically for anti-Tr. cruzi serum IgG antibody = (228)=20 (BIII). Persons who lived <6 months in a Chagas'-endemic area = but who=20 had high-risk living conditions (e.g., having had extensive = exposure to=20 the Chagas' disease vector --- the reduviid bug --- or having = lived in=20 dwellings with mud walls, unmilled logs and sticks, or a thatched = roof)=20 should also be screened for evidence of Tr. cruzi infection = (BIII).=20 Because Chagas' disease can be transmitted congenitally, = researchers=20 report that any person with extensive multigenerational maternal = family=20 histories of cardiac disease (e.g., cardiomegaly and arrhythmias) = should=20 be screened serologically for serum IgG anti-Tr. cruzi = antibodies=20 (227) (CIII). To decrease the risk for misdiagnosis by=20 false-positive or false-negative serologic tests, Tr. cruzi = screening should consist of >2 conventional serologic = tests=20 (e.g., enzyme immunoassay, indirect hemagglutination, indirect = fluorescent=20 antibody) or >1 conventional serologic tests, followed = by a=20 confirmatory serologic test (e.g., radioimmunoprecipitation assay) = (229) (BIII). Persons with active Chagas' disease should = not serve=20 as HSCT donors (DIII). Researchers also recommend deferral of HSCT = donation for a past history of Chagas' disease (CIII).

Preventing Disease

HSCT candidates who are at risk for being infected with Tr.=20 cruzi should be screened for serum IgG anti-Tr. cruzi = antibody=20 (228) (BIII). Tr. cruzi seropositivity is not a=20 contraindication to HSCT (228,230). However, if an acute = illness=20 occurs in a Tr. cruzi-seropositive HSCT recipient, = particularly=20 during neutropenia, Tr. cruzi reactivation should be = included in=20 the differential diagnosis (230) (BIII). Researchers have = proposed=20 use of beznidazole or nifurtimox for preemptive therapy or = prophylaxis of=20 recurrent Tr. cruzi among seropositive HSCT recipients=20 (230,231), but insufficient data were found to make a=20 recommendation.*****

Other Recommendations

Recommendations are the same for autologous or allogeneic = recipients.=20 However, recurrence of Chagas' disease is probably less likely to = occur=20 among autologous recipients because of the shorter duration of=20 immunosuppression. Recommendations are the same among children or = adults.=20
HOSPITAL INFECTION CONTROL

Room Ventilation

HSCT center personnel should follow published guidelines for = hospital=20 room design and ventilation (140,180) (BIII). HSCT centers = should=20 also prevent birds from gaining access to hospital air-intake = ducts=20 (140,174) (AII). All allogeneic recipients should be placed = in=20 rooms with >12 air exchanges/hour (232,233) and = point-of-use=20 HEPA filters that are capable of removing particles >0.3 = =B5m in=20 diameter (140,178,180,233) (AIII). Correct filtration is = critical=20 in HSCT centers with ongoing construction and renovation = (179).=20 When portable HEPA filters are used as adjuncts to the primary = ventilation=20 system, they must be placed centrally in patient rooms so that = space is=20 available around all surfaces to allow free air circulation = (BIII). The=20 need for environmental HEPA filtration for autologous recipients = has not=20 been established. However, HEPA-filtered rooms should be evaluated = for=20 autologous recipients if they experience prolonged neutropenia, a=20 substantial risk factor for nosocomial aspergillosis (CIII).

A laminar air flow (LAF) room contains filtered air that moves = in=20 parallel, unidirectional flow --- the air enters the room from one = wall=20 and exits the room on the opposite wall (232). Although LAF = has=20 been demonstrated to protect patients from infection during = aspergillosis=20 outbreaks related to hospital construction (234,235), the = value of=20 routine LAF room use for all HSCT recipients is doubtful because=20 substantial overall survival benefit has not been reported = (236).=20 During 1983, LAF rooms were preferred for allogeneic recipients = with=20 aplastic anemia and HLA-identical sibling donors because use of = regular=20 rooms was associated with a mortality rate that was approximately = four=20 times higher than for those recipients treated in LAF rooms = (237).=20 However, the survival of aplastic anemia HSCT recipients during = the late=20 1990s exceeds that reported during the early 1980s, and no studies = have=20 been done to determine whether HSCT recipients with aplastic = anemia still=20 have an improved survival rate when treated in an LAF room. = Therefore,=20 HSCT centers need not construct LAF rooms for each HSCT recipient. = Use of=20 LAF rooms, if available, is optional (CII).

Hospital rooms should have directed airflow so that air intake = occurs=20 at one side of the room and air exhaust occurs at the opposite = side=20 (140) (BIII). Each hospital room should also be well-sealed = (e.g,=20 around windows and electrical outlets) (140) (BIII). To = provide=20 consistent positive pressure in the recipient's room, HSCT centers = should=20 maintain consistent pressure differentials between the patient's = room and=20 the hallway or anteroom at >2.5 Pa (i.e., 0.01 inches by water = gauge)=20 (232,233) (BIII). Generally, hospital rooms for HSCT = recipients=20 should have positive room air pressure when compared with any = adjoining=20 hallways, toilets, and anterooms, if present.

Anterooms should have positive air pressure compared with = hallways=20 (180). An exception is the HSCT recipient with an active = disease=20 that has airborne transmission (e.g., pulmonary or laryngeal=20 Mycobacteria tuberculosis [TB] or measles). These HSCT = patients=20 should be placed in negative isolation rooms (62) (BIII), = and a=20 room with an anteroom is recommended for such patients = (180)=20 (BIII).

Whenever possible, HSCT centers should have self-closing doors = to=20 maintain constant pressure differentials among the HSCT = recipients' room=20 and anterooms, if available, and hallways (233) (BIII). To = enable=20 the nursing staff to observe the HSCT recipient even when the = doors are=20 closed, windows can be installed in either the door or the wall of = the=20 HSCT recipient's room (233) (CIII).

HSCT centers should provide backup emergency power and = redundant=20 air-handling and pressurization systems to maintain a constant = number of=20 air exchanges and room pressurization in the center when the = central=20 ventilation system is shut off for maintenance and repair = (238)=20 (BIII). Additionally, infection control personnel should work with = maintenance personnel to develop protocols to protect HSCT centers = at all=20 times from bursts of mold spores that might occur when = air-handling=20 systems are restarted after routine maintenance shut-downs (BIII). =

Construction, Renovation, and Building Cleaning

Construction and Renovation

Hospital construction and renovation have been associated with = an=20 increased risk for nosocomial fungal infection, particularly=20 aspergillosis, among severely immuno-compromised patients=20 (175,176). Therefore, persons responsible for HSCT center=20 construction or renovation should consult published = recommendations=20 regarding environmental controls during construction = (239,240)=20 (AIII).

Whenever possible, HSCT recipients, HCWs, and visitors should = avoid=20 construction or renovation areas (240) (AIII). Also, = equipment and=20 supplies used by HSCT recipients or their HCWs should not be = exposed to=20 construction or renovation areas (240). When planning for=20 construction or renovation, the HSCT center should include plans = for=20 intensified aspergillosis-control measures (AIII). Construction = and=20 renovation infection control planning committees should include = engineers,=20 architects, housekeeping staff, infection control personnel, the = director=20 of the HSCT center, the administration, and safety officers = (241)=20 (BIII).

When constructing new HSCT centers, planners should ensure that = patient=20 rooms will have adequate capacity to minimize fungal spore counts = by=20 following room ventilation recommendations. During outdoor = construction=20 and demolition, the intake air should be sealed (BIII), if = possible; if=20 not, filters should be checked frequently. Additionally, to = protect HSCT=20 patient care areas during fire drills and emergencies, weather = stripping=20 should be placed around stairwell doors, or alternatively, the = stairwell=20 air should be filtered to the level of safety of the adjacent = hospital air=20 (BIII). False ceilings should be avoided whenever possible = (174)=20 (BII). If use of false ceilings cannot be avoided, the area above = false=20 ceilings should be vacuumed routinely to minimize dust and, = therefore,=20 fungal exposure to patients (174) (BIII).

During hospital construction or renovation, hospitals should = construct=20 rigid, dust-proof barriers with airtight seals (242) = between=20 patient care and construction or renovation areas to prevent dust = from=20 entering patient care areas; these barriers (i.e., sealed drywall) = should=20 be impermeable to Aspergillus species = (140,175,176,179,240)=20 (BIII). If impervious barriers cannot be created around the = construction=20 or renovation area, patients should be moved from the area until=20 renovation or construction is complete and the area has been = cleaned=20 appropriately (176) (BIII). HSCT centers should direct = pedestrian=20 traffic occurring near construction or renovation areas away from = patient=20 care areas to limit the opening and closing of doors or other = barriers=20 that might cause dust dispersion, entry of contaminated air, or = tracking=20 of dust into patient areas (140), particularly those in the = HSCT=20 center (176) (BIII). If possible, specific corridors, = entrances,=20 and exits should be dedicated to construction use only = (240). An=20 elevator to which patients do not have access also should be = dedicated to=20 construction use only (240). Construction workers, whose = clothing=20 might be contaminated with Aspergillus species spores, = should use=20 the construction elevator and avoid contact with patients, patient = care=20 areas, other elevators, and nonconstruction areas (BIII).

Hospital construction or renovation areas should have negative = air=20 pressure relative to that in adjacent patient care areas, if no=20 contraindications exist for such pressure differential=20 (140,176,179,240,242) (BIII). Ideally, air from the = construction or=20 renovation areas should be exhausted to the outside of the = hospital=20 (176) (BIII) or if recirculated, it should be HEPA-filtered = first=20 (BIII).

Researchers have proposed that HSCT recipients wear the N95 = respirator=20 to prevent mold exposure during transportation near hospital = construction=20 or renovation areas (CIII) because the N95 respirators are = regarded as=20 effective against any aerosol. However, to be maximally effective, = N95=20 respirators must be fit-tested and all users must be trained. With = correct=20 personnel fit-testing and training, N95 respirators reliably = reduce=20 aerosol exposure by 90%. Without fit-testing and training, aerosol = exposure would be reduced but not necessarily by 90% (243). = For=20 patients who cannot use or tolerate an N95 respirator, researchers = have=20 proposed using the powered air purifying respirator = (244,245),=20 which can be used by patients in wheelchairs. Limitations of the = powered=20 air purifying respirator include its cost and that it is not = appropriate=20 for young children and infants. General limitations of using = respirators=20 are that no commercially available respi rator, including N95, has = been=20 tested specifically for its efficacy in reducing exposure to=20 Aspergillus species in hospital construction or renovation = areas,=20 and no studies have been done that assess the usefulness and = acceptability=20 of using respirators among HSCT recipients. Standard surgical = masks=20 provide negligible protection against mold spores and are not = recommended=20 for this indication (DIII).

Newly constructed or renovated areas should be cleaned before = patients=20 are allowed to enter them (140,176) (AIII). Decontamination = of=20 fungal-contaminated areas that cannot be extracted and replaced = should be=20 done using copper-8-quinolate (179) (BIII). Also, areas = above false=20 ceilings located under or adjacent to construction areas should be = vacuumed (174) (BIII). Additionally, the ventilation, = direction of=20 airflow, and room pressurization should be tested and correctly = adjusted=20 before patients are allowed to enter (BIII).

Cleaning

HSCT centers should be cleaned >1 times/day with = special=20 attention to dust control (BIII). Exhaust vents, window sills, and = all=20 horizontal surfaces should be cleaned with cloths and mop heads = that have=20 been premoistened with an FDA- or Environmental Protection Agency=20 (EPA)-registered hospital disinfectant (BIII). Thorough cleaning = during=20 and after any construction activity, including minor renovation = projects,=20 is critical (BIII).

HSCT center personnel should prohibit exposures of patients to = such=20 activities as vacuuming or other floor or carpet vacuuming that = could=20 cause aerosolization of fungal spores (e.g., Aspergillus = species)=20 (140) (AIII). Accordingly, doors to patient rooms should be = closed=20 when vacuuming HSCT center corridors. All vacuum cleaners used in = the HSCT=20 center should be fitted with HEPA filters. An FDA- or = EPA-registered=20 disinfectant (246,247) should be used daily for = environmental=20 disinfection and when wet vacuuming is performed in the HSCT = center=20 (BIII). If an HSCT center provides care for infants, phenolic=20 disinfectants can be used to clean the floors only if the compound = is=20 diluted according to the product label; but phenolic compounds = should not=20 be used to clean basinets or incubators (246) (DIII).

Water leaks should be cleaned up and repaired as soon as = possible but=20 within 72 hours to prevent mold proliferation in floor and wall = coverings,=20 ceiling tiles, and cabinetry in and around all HSCT patients care = areas=20 (BIII). If cleanup and repair are delayed >72 hours = after the=20 water leak, the involved materials should be assumed to contain = fungi and=20 handled accordingly. Use of a moisture meter to detect water = penetration=20 of walls should be used whenever possible to guide decision-making = (238) (BIII). For example, if the wall does not have = <20%=20 moisture content >72 hours after water penetration, it = should be=20 removed (BIII). Design and selection of furnishings should focus = on=20 creating and maintaining a dust-free environment. Flooring and = finishes=20 (i.e., wall coverings, window shades, and countertops) used in = HSCT=20 centers should be scrubbable, nonporous, easily disinfected, and = they=20 should collect minimal dust (BIII).

Isolation and Barrier Precautions

HSCT center personnel should follow published guidelines for = hospital=20 isolation practices, including CDC guidelines for preventing = nosocomial=20 infections (62,140,248) (AIII). However, the efficacy of = specific=20 isolation and barrier precautions in preventing noso-comial = infections=20 among HSCT recipients has not been evaluated.

HSCT recipients should be placed in private (i.e., = single-patient)=20 rooms (BIII). If contact with body fluids is anticipated, standard = precautions should be followed (AIII). These precautions include = hand=20 washing and wearing appropriate gloves, surgical masks or eye and = face=20 protection, and gowns during procedures and activities that are = likely to=20 generate splashes or sprays of blood, body fluids, secretions or=20 excretions, or cause soiling of clothing (62). When = indicated, HSCT=20 recipients should also be placed on airborne, droplet, or contact=20 precautions in addition to standard precautions (62) = (AIII).=20 Careful observation of isolation precautions is critical in = preventing=20 transmission of infectious agents among HSCT recipients, HCWs, = visitors,=20 and other HSCT recipients. Physicians are cautioned that HSCT = recipients=20 might have a prolonged or episodic excretion of organisms (e.g., = CMV).=20

Researchers have proposed that HSCT recipients wear surgical = mask and=20 gloves when exiting their hospital rooms before engraftment = (CIII). All=20 HSCT recipients who are immunocompromised (phases I--III of immune = system=20 recovery) and candidates undergoing conditioning therapy should = minimize=20 the time spent in crowded areas of the hospital (e.g., waiting = areas and=20 elevators) (BIII) to minimize potential exposure to persons with = CRV=20 infections.

Hand Hygiene

Hand washing is the single-most critical and effective = procedure for=20 preventing nosocomial infection (62). All persons, but = particularly=20 HCWs, should wash their hands before entering and after leaving = the rooms=20 of HSCT recipients and candidates undergoing conditioning therapy=20 (62,249) or before and after any direct contact with = patients=20 regardless of whether they were soiled from the patient, = environment, or=20 objects (AI). HSCT recipients should be encouraged to practice = safe hand=20 hygiene (e.g., washing hands before eating, after using the = toilet, and=20 before and after touching a wound) (BIII). Hand washing should be = done=20 with an antimicrobial soap and water (AIII); alternatively, use of = hygienic hand rubs is another acceptable means of maintaining hand = hygiene=20 (250,251). If gloves are worn, HCWs should put them on in = the=20 patient's room after hand washing and then discard them in the = same=20 patient's room before washing hands again after exiting the room. = When=20 worn, gloves should always be changed between patients or when = soiled=20 before touching a clean area (e.g., change gloves after touching = the=20 perineum and before going to a "clean" area) (AIII). Appropriate = gloves=20 should be used by all persons when handling potentially = contaminated=20 biological materials (AII). Items worn on the hands and fingers = (e.g.,=20 rings or artificial nails [248,252]) and adhesive bandage = strips,=20 can create a nidus for pathogenic organisms that is difficult to = clean.=20 Thus, HCWs should avoid wearing such items whenever possible = (BII).

Equipment

All HSCT center personnel should sterilize or disinfect and = maintain=20 equipment and devices using only EPA-registered compounds as = directed by=20 established guidelines (140,180,246,247,253--256) (AIII). = HSCT=20 center personnel should monitor opened and unopened wound-dressing = supplies (e.g., adhesive bandages [257,258] and surgical = and=20 elastic adhesive tape [259]) to detect mold contamination = and=20 prevent subsequent cutaneous transmission to patients (BII).

Monitoring should consist of discarding all bandages and wound=20 dressings that are out of date, have damaged packaging, or are = visually=20 contaminated by construction debris or moisture (BIII). When arm = boards=20 are used to provide support for intravenous lines, only sterile = dressing=20 materials should be used (260), and arm boards should be = changed=20 frequently (e.g., daily) (BIII). Additionally, unsterile tongue = depressors=20 inserted into a piece of foam tubing should not be used as splints = for=20 intravenous and arterial catheter sites because these have been = associated=20 with an outbreak of fatal invasive nosocomial Rhizopus = microsporus=20 among preterm (i.e., very low-birth--weight) infants (261) = (DII).=20 HSCT centers should not install carpeting in hallways outside = (DII) or in=20 patient rooms (DIII) because contaminated carpeting has been = associated=20 with outbreaks of aspergillosis among HSCT recipients = (262,263).=20

Plants, Play Areas, and Toys

Although to date, exposure to plants and flowers has not been=20 conclusively reported to cause fungal infections among HSCT = recipients,=20 most researchers strongly recommend that plants and dried or fresh = flowers=20 should not be allowed in the rooms of hospitalized HSCT candidates = undergoing conditioning therapy and HSCT recipients (phases I--III = of=20 immune system recovery) because Aspergillus species have = been=20 isolated from the soil of potted ornamental plants (e.g., cacti), = the=20 surface of dried flower arrangements, and fresh flowers=20 (140,174,178,264) (BIII).

Play areas for pediatric HSCT recipients and candidates = undergoing=20 conditioning therapy should be cleaned and disinfected = >1=20 times/week and as needed (BIII). Only toys, games, and videos that = can be=20 kept clean and disinfected should be allowed in the HSCT center = (BIII).=20 HSCT centers should follow published recommendations for washing = and=20 disinfecting toys (265) (BIII). All HSCT center toys, = games, and=20 videos should be routinely and thoroughly washed or wiped down = when=20 brought into the HSCT center and thereafter >1 = times/week and as=20 needed by using a nontoxic FDA- or EPA-registered disinfectant=20 (246,247,265) followed by a water rinse (BIII). Cloth or = plush toys=20 should be washed in a hot cycle of a washing machine or = dry-cleaned=20 >1 times/week and as needed (BIII). Alternatively, = machine=20 washing in a cold cycle is acceptable if laundry chemicals for = cold water=20 washing are used in proper concentration (265). Hard = plastic toys=20 should be scrubbed with warm soapy water using a brush to clean = crevices,=20 rinsed in clean water, immersed in a mild bleach solution, which = should be=20 made fresh daily, for 10--20 minutes, rinsed again, and allowed to = air dry=20 (246). Alternatively, hard plastic toys can be washed in a=20 dishwasher or hot cycle of a washing machine (BIII). Broviac = dolls******=20 should be disassembled upon completion of play and washed with a = nontoxic=20 FDA- or EPA-registered disinfectant (246,247), rinsed with = tap=20 water, and allowed to air dry before other children are allowed to = play=20 with them (BIII). Toys that cannot be washed, disinfected, or = dry-cleaned=20 after use should be avoided (BIII). Infants, toddlers, and = children who=20 put toys in their mouths should not share toys (265) = (DIII). For=20 children in isolation, researchers recommend the following:=20

Disposable play items should be offered whenever possible = (BIII).=20
Before returning a washable toy used in an isolation room to = the=20 pediatric play room for use by another child, it should be = cleaned again=20 as previously described (BIII).=20
When a child is taken out of isolation, toys, games, and = videos used=20 during the period of isolation and that might serve as fomites = for=20 infection should be thoroughly disinfected with a nontoxic FDA- = or=20 EPA-registered disinfectant (246,247,265) (BIII). After = use in=20 isolation rooms, cloth or plush toys should be placed in a = plastic bag=20 and separated from unused toys. All cloth or plush toys used in=20 isolation rooms should be washed in a washing machine or = dry-cleaned=20 before being used in a nonisolation room (BIII). Toys that = cannot be=20 disinfected or dry-cleaned after use in an isolation room should = be=20 discarded (BIII).
Water-retaining bath toys have been = associated=20 with an outbreak of Pseudomonas aeruginosa in a pediatric = oncology=20 ward (266); therefore, these toys should not be used by=20 immunocompromised HSCT recipients and candidates (DII). = Occupational and=20 physical therapy items should be cleaned and disinfected as = previously=20 described (BIII). Soil-based materials (e.g., clay or potting = soil) should=20 be avoided (BIII).=20
HCWs

HSCT center personnel should have a written comprehensive = policy=20 regarding their immunizations and vaccinations, and that policy = should=20 meet current CDC, Advisory Committee on Immunization Practices, = and=20 Healthcare Infection Control Practices Advisory Committee = recommendations=20 (267) (BIII). Immunizations are needed to prevent = transmission of=20 vaccine-preventable diseases to HSCT recipients and candidates = undergoing=20 conditioning therapy. All HCWs with diseases transmissible by air, = droplet, and direct contact (e.g., VZV, infectious = gastroenteritis, HSV=20 lesions of lips or fingers, and URIs) should be restricted from = patient=20 contact and temporarily reassigned to other duties (AI). HSCT = center=20 personnel should follow published recommendations regarding the = duration=20 of work restrictions for HCWs with infectious diseases = (268,269)=20 (BIII). HSCT center HCWs with bloodborne viruses (e.g., HIV or = hepatitis B=20 or C viruses) should not be restricted from patient contact (DIII) = as long=20 as they do not perform procedures that pose a high risk for injury = that=20 could result in patient exposure to the HCW's blood or body = fluids. Work=20 exclusion policies should be designed to encourage HCWs to report = their=20 illnesses or exposures (AII).

HSCT Center Visitors

Hospitals should have written policies for screening HSCT = center=20 visitors, particularly children, for potentially infectious = conditions.=20 Such screening should be performed by clinically trained HCWs = (BII).=20 Visitors who might have communicable infectious diseases (e.g., = URIs,=20 flu-like illnesses, recent exposure to communicable diseases, an = active=20 shingles rash whether covered or not, a VZV-like rash within 6 = weeks of=20 receiving a live-attenuated VZV vaccine, or a history of receiving = an oral=20 polio vaccine within the previous 3--6 weeks) should not be = allowed in the=20 HSCT center or allowed to have direct contact with HSCT recipients = or=20 candidates undergoing conditioning therapy (AII). No absolute = minimum age=20 requirement for HSCT center visitors exists; however, all visitors = must be=20 able to understand and follow appropriate hand washing and = isolation=20 precautions (AIII). The number of HSCT center visitors at any one = time=20 should be restricted to a number that permits the nursing staff to = perform=20 appropriate screening for contagious diseases and adequate = instruction and=20 supervision of hand washing, glove and mask use, and biosafety = precautions=20 (BIII).

Patient Skin and Oral Care

To optimize skin care, HSCT recipients should take daily = showers or=20 baths during and after transplantation (BIII), using a mild soap = (BIII).=20 Skin care during neutropenia should also include daily inspection = of skin=20 sites likely to be portals of infection (e.g., the perineum and=20 intravascular access sites) (BIII). HSCT recipients and candidates = undergoing conditioning therapy should maintain good perineal = hygiene to=20 minimize loss of skin integrity and risk for infection (BIII). To=20 facilitate this precaution, HSCT center personnel should develop = protocols=20 for patient perineal care, including recommendations for gentle = but=20 thorough perineal cleaning after each bowel movement and thorough = drying=20 of the perineum after each urination (BIII). Females should always = wipe=20 the perineum from front to back after using the toilet to prevent = fecal=20 contamination of the urethra and urinary tract infections (AIII).=20 Moreover, to prevent vaginal irritation, menstruating = immunocompromised=20 HSCT recipients should not use tampons (DIII) to avoid the risk = for=20 cervical and vaginal abrasions. Additionally, the use of rectal=20 thermometers, enemas, suppositories, and rectal exams are = contraindicated=20 among HSCT recipients to avoid skin or mucosal breakdown (DIII). =

All HSCT candidates and their caregivers should be educated = regarding=20 the importance of maintaining good oral and dental hygiene for at = least=20 the first year after HSCT to reduce the risk for oral and dental=20 infections (AIII). For example, HSCT candidates should be informed = that=20 establishment of the best possible periodontal health before HSCT = is a=20 substantial step in avoiding short- and long-term oral infections = and that=20 maintenance of safe oral hygiene after HSCT can minimize the = severity of=20 infections and facilitate healing of mucositis, particularly = before=20 engraftment (BIII).

All HSCT candidates should receive a dental evaluation and = relevant=20 treatment before conditioning therapy begins (270,271) = (AIII).=20 Likely sources of dental infection should be vigorously eliminated = (271) (AIII). For example, teeth with moderate to severe = caries=20 should be restored; ill-fitting dental prostheses should be = repaired; and=20 teeth compromised by moderate to severe periodontal disease should = be=20 extracted (271). Ideally, 10--14 days should elapse between = the=20 completion of tissue-invasive oral procedures and onset of = conditioning=20 therapy to allow for adequate healing and monitoring for = postsurgical=20 complications (AIII).

HSCT recipients with mucositis and HSCT candidates undergoing=20 conditioning therapy should maintain safe oral hygiene by = performing oral=20 rinses 4--6 times/day with sterile water, normal saline, or sodium = bicarbonate solutions (270) (AIII). HSCT recipients and = candidates=20 should brush their teeth >2 times/day with a soft = regular=20 toothbrush (270) (BIII). If the recipient cannot tolerate = these=20 brushings, use of an ultrasoft toothbrush or toothette (i.e., foam = swab on=20 a stick), can be used (CIII), but physicians should be aware that = using=20 the latter products are less desirable than using soft regular or=20 ultrasoft toothbrushes because the toothettes remove less dental = debris=20 (270). Using toothpaste is optional, depending on the = recipient's=20 tolerance (270) (CIII). HSCT recipients and candidates = undergoing=20 conditioning therapy who are skilled at dental flossing should = floss daily=20 if this can be done without trauma (BIII). Routine dental = supervision is=20 advised to monitor and guide the patient's maintenance of oral and = dental=20 hygiene (BIII). To decrease the risk for mechanical trauma and = infection=20 of oral mucosa, fixed orthodontic appliances and space maintainers = should=20 not be worn from the start of conditioning therapy until = preengraftment=20 mucositis resolves, and these devices should not be worn during = any=20 subsequent periods of mucositis (270) (DIII). Dental and = transplant=20 teams and the patient's community dentist should coordinate = removal of=20 these appliances and long-term rehabilitation of any oral lesions = (BIII).=20 However, patients who normally wear removable dental prostheses = might be=20 able to wear them during conditioning therapy before HSCT and = during=20 mucositis after HSCT, depending on the degree of tissue integrity = at the=20 denture-bearing sites and the ability of the patient to maintain = denture=20 hygiene on a daily basis (CIII).

Preventing Bacterial Intravascular Catheter-Related = Infections=20

HSCT center personnel are advised to implement published = guidelines for=20 preventing intravascular device-related infections (33) = (AIII).=20 Contact with tap water at the central venous catheter site should = be=20 avoided (BIII). For long-term central venous access among = children, HSCT=20 physicians can use a totally implantable device among children = aged <4=20 years if the anticipated duration of vascular access is >30 = days (CII).=20 However, such a device among children aged <4 years is not = generally=20 used as the actual HSCT infusion site because a) problems with = skin=20 fragility contraindicate repeated punctures over the port site and = b) the=20 port device might have an insufficient number of lumens for = optimal=20 patient management immediately after HSCT.

To prevent bloodstream infections associated with needleless=20 intravenous access devices, HSCT recipients should a) cover and = protect=20 the catheter tip or end cap during bathing or showering to protect = it from=20 tap water contamination, b) change the device in accordance with=20 manufacturers' recommendations, if available, and c) have a = caregiver=20 perform intravenous infusions whenever possible (272,273) = (BII).=20 Also, HSCT recipients and their caregivers should be educated = regarding=20 proper care of needleless intravenous access devices (272) = (BII).=20 No recommendation regarding the use of antibiotic-impregnated = central=20 venous catheters among HSCT recipients can be made because of lack = of=20 data.

Control of Specific Nosocomial Infections

Recommendations Regarding Legionella = Species

HSCT physicians should always include Legionnaires' disease = (LD) in the=20 differential diagnosis of pneumonia among HSCT recipients = (140)=20 (AIII). Appropriate tests to confirm LD include a) culturing = sputum, BAL,=20 and tissue specimens; b) testing BAL specimens for = Legionellae by=20 direct fluorescent antibody; and c) testing for Legionella=20 pneumophila serogroup 1 antigen in urine. The incubation = period for LD=20 is usually 2--10 days; thus, laboratory-confirmed legionellosis = that=20 occurs in a patient who has been hospitalized continuously for=20 >10 days before the onset of illness is regarded as a = definite=20 case of nosocomial LD, and a laboratory-confirmed infection that = occurs=20 2--9 days after hospital admission is a possible case of = nosocomial LD=20 (140). When a case of laboratory-confirmed nosocomial LD=20 (274,275) is identified in a person who was in the = inpatient HSCT=20 center during all or part of the 2--10 days before illness onset, = or if=20 two or more cases of laboratory-confirmed LD occur among patients = who had=20 visited an outpatient HSCT center, hospital personnel should=20

report the case(s) to the local or state health department = if the=20 disease is reportable in that state or if assistance is needed=20 (140) (AIII); and=20
in consultation with the hospital infection control team, = conduct a=20 thorough epidemiologic and environmental investigation to = determine the=20 likely environmental source(s) of Legionella species = (e.g.,=20 showers, tap water faucets, cooling towers, and hot water tanks) = (274,276) (AI).

The source of Legionella infection should be identified = and=20 decontaminated or removed (AIII). Extensive hospital = investigations of an=20 isolated case of possible nosocomial LD might not be indicated if = the=20 patient has had limited contact with the inpatient center during = most of=20 the incubation period (CIII). Because HSCT recipients are at much = higher=20 risk for disease and death from legionellosis compared with other=20 hospitalized persons (274), periodic routine culturing for=20 Legionellae in water samples from the center's potable = water supply=20 could be regarded as part of an overall strategy for preventing LD = in HSCT=20 centers (CIII). However, the optimal methodology (i.e., frequency = or=20 number of sites) for environmental surveillance cultures in HSCT = centers=20 has not been determined, and the cost-effectiveness of this = strategy has=20 not been evaluated. Because HSCT recipients are at high risk for = LD and no=20 data were found to determine a safe concentration of = Legionellae=20 organisms in potable water, the goal, if environmental = surveillance for=20 Legionellae is undertaken, should be to maintain water = systems with=20 no detectable organisms (AIII). Physicians should suspect = legionellosis=20 among HSCT recipients with nosocomial pneumonia even when = environmental=20 surveillance cultures do not yield Legionellae (AIII). If=20 Legionella species are detected in the water supplying an = HSCT=20 center, the following should be done until Legionella = species are=20 no longer detected by culture:=20

The water supply should be decontaminated (140) = (AII).=20
HSCT recipients should be given sponge baths with water that = is not=20 contami-nated with Legionella species (e.g., not with the = HSCT=20 center's Legionella species-contaminated potable water = system)=20 (BIII).=20
Patients should not take showers in LD-contaminated water = (DIII).=20
Water from faucets containing LD-contaminated water should = not be=20 used in patient rooms or the HSCT center and outpatient clinic = to avoid=20 creating infectious aerosols (CIII).=20
HSCT recipients should be given sterile water instead of tap = water=20 for drinking, brushing teeth, or flushing nasogastric tubes = during=20 Legionellosis outbreaks (BIII).
HSCT center personnel = should use=20 only sterile water (i.e., not distilled unsterile water) for = rinsing=20 nebulization devices and other semicritical respiratory-care = equipment=20 after cleaning or disinfecting and for filling reservoirs of = nebulization=20 devices (140) (BII). HSCT centers should not use = large-volume room=20 air humidifiers that create aerosols (e.g., by Venturi principle,=20 ultrasound, or spinning disk) and, thus, are actually nebulizers=20 (140) (DI) unless these humidifier or nebulizers are = sterilized or=20 subjected to daily high-level disinfection and filled with sterile = water=20 only (140) (CIII).=20
When a new hospital with an HSCT center is constructed, the = cooling=20 towers should be placed so that the tower drift is directed away = from the=20 hospital's air-intake system, and the cooling towers should be = designed so=20 that the volume of aerosol drift is minimized (140) (BII). = For=20 operational hospital cooling towers, hospitals should=20

install drift eliminators,=20
regularly use an effective biocide,=20
maintain cooling towers according to the manufacturer's=20 recommendations, and=20
keep adequate maintenance records (140) (BII). =
HSCT=20 physicians are encouraged to consult published recommendations = regarding=20 preventing nosocomial Legionellosis (140,277) (BIII). No = data were=20 found to determine whether drinking tap water poses a risk for=20 Legionella exposure among HSCT recipients in the absence of = an=20 outbreak.=20
Recommendations Regarding Methicillin-Resistant Sta.=20 aureus

HSCT center HCWs should follow basic infection control = practices (e.g.,=20 hand washing between patients and use of barrier precautions, = including=20 wearing gloves whenever entering the methicillin-resistant Sta. = aureus [MRSA] infected or colonized patient's room); these = practices=20 are essential for MRSA control (62) (AII). If MRSA is a = substantial=20 problem in the HSCT center and evidence exists of ongoing MRSA=20 transmission, MRSA infected or colonized patients should be = treated as a=20 cohort (e.g., cared for exclusively by a limited number of HCWs) = (BIII).=20 HSCT transplant recipients with recurrent Sta. aureus = infections=20 should undergo extensive evaluation for persistent colonization, = including=20 cultures of nares, groin, axilla, and ostomy sites (e.g., = tracheostomy or=20 gastrointestinal tube) (BIII). For patients with recurrent MRSA = infection,=20 elimination of the carrier state should be attempted by applying a = 2%=20 mupirocin calcium ointment to the nares (BIII), although this = strategy has=20 been only marginally effective in certain institutions = (278) (Appen= dix).=20 High-level mupirocin-resistant MRSA has been reported in Europe, = the=20 Middle East, and South America (279--283) but is uncommon = in the=20 United States. As with any antibiotic, incorrect or overuse of = mupirocin=20 can result in mupirocin-resistant Staphylococci; therefore, = mupirocin use should be reserved for infection control strategies = only=20 (279,280). For patients who fail mupirocin, physicians have = used=20 bacitracin, TMP-SMZ, or rifampin administered with another = antibiotic, but=20 no standardized protocol using these drugs for this indication has = been=20 evaluated and no recommendations can be made because of lack of = data.=20 Selection of a systemic antibiotic should be guided by = susceptibility=20 patterns.

Intravascular cannulas or other implantable devices that are = infected=20 or colonized with MRSA should be removed (AIII). Patients with = MRSA should=20 be placed under contact precautions until all antibiotics are = discontinued=20 and until three consecutive cultures, taken >1 weeks = apart, are=20 negative (62) (BIII). Screening cultures for MRSA include = the=20 anterior nares, any body site previously positive for MRSA, and = any wounds=20 or surgical sites.

Recommendations Regarding Staphylococcus Species = with=20 Reduced Susceptibility to Vancomycin

All HSCT centers should have sufficient laboratory capability = to=20 identify all Staphylococci isolates and their = susceptibility=20 patterns to antibiotics, including vancomycin (284,285) = (AIII).=20 Additionally, all HSCT center personnel should conduct routine=20 surveillance for the emergence of Staphylococcus species = strains=20 with reduced susceptibility to vancomycin (285,286) (AIII). = Reduced=20 susceptibility should be considered for all Sta. aureus = strains=20 that have a vancomycin MIC of >4 =B5g/mL and all=20 coagulase-negative Staphylococci that have a vancomycin MIC = of=20 >8 =B5g/mL. If repeat testing of the organism in pure = culture=20 confirms the genus, species, and elevated vancomycin MICs, the = following=20 steps should be taken (287):=20

The laboratory should immediately contact hospital infection = control=20 personnel, the patient's clinical center, and the patient's = attending=20 physician, as well as the local or state health department, and = CDC's=20 Hospital Infections Program Help Desk ([404] 639-6106 or [800] = 893-0485)=20 (284,285,287,288) (AIII).=20
The HSCT center's infection control personnel, in = collaboration with=20 appropriate authorities (i.e., state and local health = departments and=20 CDC) should promptly initiate an epidemiologic and laboratory=20 investigation (287,288) (AIII) and follow published = guidelines=20 for the control of such species (285,287,288) (BIII).=20
Medical and nursing staff should=20

institute contact precautions (e.g., wearing of gown and = gloves,=20 using antibacterial soap for hand washing, and wearing masks = when=20 contamination of the HCW with secretions is likely) as = recommended for=20 multidrug-resistant organisms (62,284,287);=20
minimize the number of persons with access to colonized or = infected patients (287); and=20
treat as a cohort colonized or infected patients (e.g., = care for=20 them exclusively with a limited number of HCWs) = (286,287)=20 (AIII).

If a patient in an HSCT center is colonized or infected with = Staphylococci that have reduced susceptibility to = vancomycin, the=20 infection control personnel should follow published guidelines = for the=20 control of such species (285,287,288) (BIII). =
Avoiding=20 overuse and misuse of antibiotics will decrease the emergence of=20 Staphylococcus species with reduced susceptibility to = vancomycin=20 (286,287). There-fore, medical and ancillary staff members = who are=20 responsible for monitoring antimicrobial use patterns in the = facility=20 should routinely review vancomycin-use patterns = (284,285,287)=20 (AIII). Additionally, HSCT center personnel should institute = prudent use=20 of all antibiotics, particularly vancomycin, to prevent the = emergence of=20 Staphylococcus with reduced susceptibility to vancomycin=20 (284,285,287--289) (AII). Intravascular cannulas or other=20 implantable devices that are infected or colonized with=20 Staphylococcus species strains with reduced susceptibility = to=20 vancomycin should be removed (AIII).=20
Recommendations Regarding VRE

Use of intravenous vancomycin is associated with VRE emergence. = Vancomycin and all other antibiotics, particularly antianaerobic = agents=20 (e.g., metronidazole and third-generation cephalosporins) must be = used=20 judiciously (284,290--292) (AII). Oral van-comycin use can = be=20 limited by treating recurrences of Cl. difficile diarrhea = with oral=20 metronidazole instead of vancomycin (BIII). Physicians have placed = patients with a history of VRE or VRE colonization into continuous = isolation during clinic visits and hospitalizations; however, this = practice is controversial because certain non-HSCT recipients = might clear=20 VRE from their stools. No recommendation regarding use of = continuous=20 isolation among HSCT recipients can be made because of lack of = data. To=20 control VRE exposure, strict adherence to the following standard = infection=20 control measures is necessary (292) (AI):=20

Wash hands with antibacterial soap before entering and after = leaving=20 HSCT recipients' rooms, particularly those who have VRE = colonization or=20 infection; alternatively, wash hands with a waterless antiseptic = agent=20 (e.g., an alcohol-based rinse or gel) (250).=20
Whenever possible, treat as a cohort patients who are known = to be=20 colonized or infected with VRE (290).=20
Disinfect patient rooms and equipment (291,293), = including=20 surfaces of the hospital ward environment (e.g., floors, walls, = bed=20 frames, doors, bathroom surfaces) with an FDA- or EPA-registered = disinfectant (246,247). A nontoxic disinfectant should be = used=20 for pediatric areas (BIII).=20
Place patients with VRE under contact precautions until all=20 antibiotics are discontinued (CIII) and repeated cultures are = negative=20 (62) (BIII). HCWs should always wear gloves when in the = VRE=20 patient or carrier's room and discard gloves in the patient's = room=20 before exiting.
No evidence exists that treating VRE = carriers is=20 beneficial; therefore, chronic antibiotic treatment of carriers is = not=20 recommended (DIII). HSCT recipients and candidates should be = screened for=20 VRE colonization at the time of interfacility transfer to allow = for=20 immediate institution of appropriate infection control practices = and to=20 minimize transmission of VRE between and within facilities = (294)=20 (BII). However, the role of outpatient surveillance in VRE control = is=20 unknown; such surveillance is costly and should not be undertaken = in=20 nonoutbreak settings (DIII). A history of having resolved VRE = bacteremia=20 or being a VRE carrier are not contraindications to HSCT (BIII).=20
Recommendations Regarding Cl. difficile

HSCT physicians should follow published recommendations for = preventing=20 and controlling Cl. difficile disease, including minimizing = the=20 duration of antibiotic therapy and number of antibiotics used for = any=20 indication (295,296) (AIII). All patients with Cl. = difficile=20 disease should be placed under contact precautions for the = duration of=20 illness (62) (AII). All HCWs who anticipate contact with a = Cl.=20 difficile-infected patient or the patient's environment or = possessions=20 should put on gloves before entering the patient's room=20 (62,295--298) and before handling the patient's secretions = and=20 excretions (AI). During Cl. difficile outbreaks, HSCT = center=20 personnel should restrict use of antibiotics (e.g., clindamycin)=20 (299) (BII). To prevent transmission of Cl. = difficile to=20 patients during nosocomial Cl. difficile outbreaks, HSCT = center=20 HCWs should a) use disposable rectal thermometers or tympanic=20 thermometers; b) disinfect gastrointestinal endoscopes with 2%=20 glutaraldehyde immersion for 10 minutes or use an equivalent = disinfectant=20 strategy (255,256); and c) perform surface sterilization of = the=20 hospital ward environment (e.g., floors, walls, bed frames, doors, = bathroom surfaces) with an FDA- or EPA-registered sterilant (e.g., = phosphate-buffered sodium hypochlorite solution [1,660 ppm = available=20 chloride]; unbuffered hypochlorite solution [500 ppm available = chloride];=20 0.04% formaldehyde and 0.03% glutaraldehyde [255,295,300]; = or=20 ethylene oxide [247,296]) (BII). Additionally, physicians = should=20 treat patients with Cl. difficile disease with antibiotics = as=20 recommended in published reports (62,295) (BII).

Certain researchers also recommend antibiotic treatment of = Cl.=20 difficile carriers (301). However, other researchers = have=20 reported that treatment of asymptomatic Cl. difficile = carriers with=20 metronidazole is not effective and that treatment with vancomycin = is only=20 effective temporarily (i.e., <2 months after treatment) = (302).=20 Consequently, no recommendation regarding treatment of = asymptomatic Cl.=20 difficile carriers can be made. Similarly, although = symptomatic Cl.=20 difficile disease recurrence or relapse occurs among 7%--20% = of=20 patients (295), data are insufficient to make a = recommendation for=20 preventing multiple Cl. difficile relapses.

The following practices are not recommended for Cl. = difficile=20 control:=20

routine stool surveillance cultures for Cl. difficile = for=20 asymptomatic patients or HCWs, even during outbreaks (DIII);=20
culturing HCWs' hands for Cl. difficile (DIII); or=20
treating patients presumptively for Cl. difficile = disease=20 pending toxin results (DIII), unless the patient is very sick = with a=20 compatible syndrome or the hospital has a high prevalence of = Cl.=20 difficile (CIII).
Prophylactic use of lyophilized=20 Saccharomyces boulardii to reduce diarrhea among antibiotic = recipients is not recommended because this therapy is not = associated with=20 a substantial reduction in diarrhea associated with Cl. = difficile=20 disease (303) and has been associated with Saccharomyces = boulardii fungemia (304) (DII).=20
Recommendations Regarding CRV Infections

Physicians should institute appropriate precautions and = infection=20 control measures for preventing nosocomial pneumonia among = hospitalized=20 HSCT recipients and candidates undergoing conditioning therapy,=20 particularly during community or nosocomial CRV outbreaks = (140)=20 (AIII). Patients with URI or LRI symptoms should be placed under = a)=20 contact precautions for most viral respiratory infections = including=20 varicella; b) droplet precautions for influenza or adenovirus; or = c)=20 airborne precautions for measles or varicella to avoid = transmitting=20 infection to other HSCT candidates and recipients as well as to = HCWs and=20 visitors (BIII). Identifying HSCT recipients with RSV infection = and=20 placing them under contact precautions immediately (AIII) to = prevent=20 nosocomial transmission is critical. When suctioning the = respiratory tract=20 of patients with URI or LRI symptoms, HCWs should wear gowns, = surgical=20 masks, and eye protection to avoid contamination from the = patient's=20 respiratory secretions. All protective clothing (e.g., gown, = gloves,=20 surgical mask, and eye protection) should be put on when entering = a=20 patient's room and discarded in the same room before exiting; = protective=20 clothing should always be changed between patient rooms = (140)=20 (AIII). When caring for an HSCT recipient or candidate undergoing=20 conditioning therapy with URI or LRI, HCWs and visitors should = change=20 gloves and wash hands a) after contact with a patient; b) after = handling=20 respiratory secretions or objects contaminated with secretions = from one=20 patient and before contact with another patient, object, or = environmental=20 surface; and c) between contacts with a contaminated body site and = the=20 respiratory tract of or respiratory device used on the same = patient=20 (140) (AII). This practice is critical because most = respiratory=20 infections are usually transmitted by contact, particularly by = hand to=20 nose and eye. Therefore just wearing a mask, without appropriate = hand=20 washing, glove-wearing, or use of eye protection is insufficient = to=20 prevent transmission of CRV infections.

Researchers have proposed that HSCT recipients or candidates = undergoing=20 conditioning therapy be placed under contact precautions during = nosocomial=20 outbreaks (131) (CIII). Even when no nosocomial or = community=20 outbreak of CRV infections exists, all persons who enter the HSCT = center=20 should be screened daily for URI symptoms, including visitors and = HCWs=20 (BIII). Researchers also describe systems where HCWs provide daily = verification (e.g., using sign-in sheets) that they are free of = URI=20 symptoms before being allowed to provide HSCT patient care. HCWs = and=20 visitors with URI symptoms should be restricted from contact with = HSCT=20 recipients and candidates undergoing conditioning therapy to = minimize the=20 risk for CRV transmission (131) (AIII). All HCWs with URI = symptoms=20 should be restricted from patient contact and reassigned to = nonpatient=20 care duties until the HCW's symptoms resolve (BIII). Visitors with = URI=20 symptoms should be asked to defer their visit to the HSCT center=20 (131) until their URI symptoms resolve (BIII).

Respiratory secretions of any hospitalized HSCT candidate or = recipient=20 with signs or symptoms of CRV infection should be tested promptly = by viral=20 culture and rapid diagnostic tests for CRV (BIII). Appropriate = samples=20 include nasopharyngeal washes, swabs, aspirates, throat swabs, and = BAL=20 fluid. This practice is critical because preemptive treatment of = certain=20 CRVs (e.g., influenza and RSV) (133) might prevent severe = disease=20 and death among HSCT recipients. Viral shedding among HSCT = recipients with=20 CRV infection has been reported to last <4 months for = influenza=20 (143), <2 years for adenovirus (305,306), = and=20 <22 days for RSV (136); however, RSV viral = shedding has=20 been reported to last 112 days in a child with severe combined=20 immunodeficiency (307). Therefore, to prevent nosocomial=20 transmission of CRV (136), HSCT center HCWs should = recognize that=20 prolonged CRV shedding can occur when determining the duration of=20 appropriate precautions for CRV-infected HSCT recipients or = candidates=20 undergoing conditioning therapy (CIII). HSCT centers should use = serial=20 testing by using cultures from nasopharyngeal swabs, throat swabs = or=20 aspirates, or rapid antigen tests to help determine whether = patients have=20 stopped shedding influenza virus (BIII). Researchers have proposed = that=20 HSCT physicians conduct routine CRV surveillance among HSCT = recipients to=20 detect outbreaks and implement infection control measures as early = as=20 possible (CIII). During RSV season, HSCT recipients and candidates = with=20 signs or symptoms should be tested for RSV infection (i.e., the = presence=20 of RSV antigen in respiratory secretions tested by enzyme-linked=20 immunosorbent assay and viral culture) starting with admission to = the HSCT=20 center. All patients who are RSV-antigen positive should be = treated as a=20 cohort during nosocomial RSV outbreaks because this practice = reduces=20 nosocomial RSV transmission (130,131) (BII). Symptomatic = HCWs=20 should be excluded from patient contact until symptoms resolve. = HCWs and=20 visitors with infectious conjunctivitis should be restricted from = direct=20 patient contact until the drainage resolves (i.e., usually, 5--7 = days for=20 adenovirus) and the ophthalmology consultant concurs that the = infection=20 and inflammation have resolved (268) (AII) to avoid = possible=20 transmission of adenovirus to HSCT recipients.

Preventing CRV exposure among HSCT recipients after hospital = discharge=20 is more challenging because of high CRV prevalence. Preventive = measures=20 should be individualized in accordance with the immunologic status = and=20 tolerance of the patient. In outpatient waiting rooms, patients = with CRV=20 infections should be separated to the extent possible from other = patients=20 (BIII).

Recommendations Regarding TB

HSCT candidates should be screened for TB by careful medical = history=20 and chart review to ascertain any history of prior TB exposure = (AIII)=20 because immunocompromised persons have higher risk for progression = from=20 latent TB infection to active disease (244). Also, = physicians can=20 administer a tuberculin skin test (TST) using the Mantoux method = with five=20 tuberculin units of purified protein derivative (CIII); but = because of a=20 patient's immunocompromise, this test might not be reliable. If a = TST is=20 administered, either the Tubersol^=AE or = Aplisol^=AE=20 formulation of purified protein derivative can be used = (244,308).=20 Persons with a recently positive TST or a history of a positive = TST and no=20 prior preventive therapy should be administered a chest radiograph = and=20 evaluated for active TB (309) (AI). For immunocompromised = persons,=20 a positive TST is defined as >5 mm of induration=20 (309,310) because of their decreased ability to mount a = delayed=20 hypersensitivity response (CIII). Because immunosuppressive = therapy=20 decreases the sensitivity of the TST, HSCT physicians should not = rely=20 solely on the TST to determine whether latent TB infection is = present and=20 whether preventive therapy should be administered to HSCT = recipients or=20 candidates (DIII). Instead, a full 9-month course of isonicotinic = acid=20 hydrazide preventive therapy should be administered to = immunocompromised=20 HSCT recipients or candidates who have been substantially exposed = to=20 someone with active, infectious (i.e., sputum-smear positive) = pulmonary or=20 laryngeal TB, regardless of the HSCT recipient's or candidate's = TST status=20 (309) (BIII). A full 9-month course of isonicotinic acid = hydrazide=20 preventive therapy should also be administered to HSCT recipients = or=20 candidates with a positive TST who were not previously treated and = have no=20 evidence of active TB disease (309) (AIII) (Appen= dix).=20 Routine anergy screening might not be reliable among HSCT = recipients and=20 candidates undergoing conditioning therapy and, therefore, is not=20 recommended (DIII). An HSCT should not be canceled or delayed = because of a=20 positive TST (DIII).

Use of a 2-month course of a daily pyrazinamide/rifampin = (PZA/RIF)=20 regimen has been recommended as an alternate preventive therapy = for=20 persons with TB (309). However, limited data were found = regarding=20 safety and efficacy of this regimen among non-HIV--infected = persons.=20 Furthermore, rifampin has substantial drug interactions with = certain=20 medications, including cyclosporine, tacrolimus (FK506), = corticosteroids,=20 fluconazole, and pain medications. Therefore, routine use of the = 2-month=20 PZA/RIF prophylactic regimen among HSCT recipients is not = recommended=20 (DIII). However, this regimen can be used for HSCT candidates who = are not=20 at risk for serious rifampin drug interactions and whose HSCT is = not=20 scheduled until >2 weeks after completion of the 2-month = PZA/RIF=20 course (CIII). This delay will diminish the possibility of adverse = effects=20 of rifampin on drugs used for routine HSCT OI prophylaxis (e.g.,=20 fluconazole) (311). An HSCT candidate or recipient who has = been=20 exposed to an active case of extrapulmonary, and therefore, = noninfectious=20 TB does not require preventive therapy (DIII).

HSCT center personnel should follow guidelines regarding the = control of=20 TB in health-care facilities (244,245), including = instituting=20 airborne precautions and negative-pressure rooms for patients with = suspected or confirmed pulmonary or laryngeal TB (62,244) = (AII).=20 HCWs should wear N95 respirators, even in isolation rooms, to = protect=20 themselves from possible TB transmission from patients with active = pulmonary or laryngeal TB, particularly during cough-inducing = procedures=20 (62,244,245,312) (AIII). To be maximally effective, = respirators=20 (e.g., N95) must be fit-tested, and all respirator users must be = trained=20 to use them correctly (243) (AIII). Unless they become = soiled or=20 damaged, changing N95 respirators between patient rooms is not = necessary=20 (DIII). Bacillus of Calmette and Gu=E9rin vaccination is = contraindicated=20 among HSCT candidates and recipients because it might cause = disseminated=20 or fatal disease among immunocompromised persons (313,314) = (EII).=20 No role has been identified for chronic suppressive therapy or = follow-up=20 surveillance cultures among HSCT recipients who have a history of=20 successfully treated TB (DIII).

Infection Control Surveillance

HSCT center personnel are advised to follow standard guidelines = for=20 surveillance of antimicrobial use and nosocomial pathogens and = their=20 susceptibility patterns (315) (BIII). HSCT center personnel = should=20 not perform routine fungal or bacterial cultures of asymptomatic = HSCT=20 recipients (166,167) (DII). In the absence of epidemiologic = clusters of infections, HSCT center personnel should not perform = routine=20 periodic bacterial surveillance cultures of the HSCT center = environment or=20 of equipment or devices used for respiratory therapy, = pulmonary-function=20 testing, or delivery of inhalation anesthesia (140) (DIII). = Researchers recommend that hospitals perform routine sampling of = air,=20 ceiling tiles, ventilation ducts, and filters to test for molds,=20 particularly when construction or renovation occurs near or around = the=20 rooms of immunocompromised patients (167,174) or when = clinical=20 surveillance demonstrates a possible increase in mold (i.e.,=20 aspergillosis) cases (CIII). Strategies that might decrease fungal = spores=20 in the ventilation system include eliminating access of birds = (i.e.,=20 primarily pigeons) to air-intake systems, removing bird droppings = from the=20 air-intake ducts, and eliminating moss from the hospital roof=20 (174). Furthermore, in the absence of a nosocomial fungal = outbreak,=20 HSCT centers need not perform routine fungal cultures of devices = and dust=20 in the rooms of HSCT recipients and candidates undergoing = conditioning=20 therapy (DIII). HSCT center personnel should routinely perform=20 surveillance for the number of aspergillosis cases occurring among = HSCT=20 recipients, particularly during hospital construction or = renovation=20 (BIII). A two-fold or greater increase in the attack rate of = aspergillosis=20 during any 6-month period indicates that the HSCT center = environment=20 should be evaluated for breaks in infection control techniques and = procedures and that the ventilation system should be investigated=20 carefully (174) (BIII).=20
STRATEGIES FOR SAFE LIVING AFTER HSCT -- PREVENTING = EXPOSURE AND=20 DISEASE

Avoiding Environmental Exposures

HSCT recipients and candidates undergoing conditioning therapy, = particularly allogeneic recipients, and parents of pediatric HSCT=20 recipients and candidates should be educated regarding strategies = to avoid=20 environmental exposures to opportunistic pathogens (AIII).

Preventing Infections Transmitted by Direct Contact =

HSCT recipients and candidates should wash their hands = thoroughly=20 (i.e., with soap and water) and often. For example, hands should = be washed=20

before eating or preparing food;=20
after changing diapers;=20
after gardening or touching plants or dirt;=20
after touching pets or animals;=20
after touching secretions or excretions or items that might = have had=20 contact with human or animal stool (e.g., clothing, bedding, = toilets, or=20 bedpans);=20
after going outdoors; and=20
before and after touching wounds (249) (AIII).=20
Conscientious hand washing is critical during the first = 6 months=20 after HSCT and during other periods of substantial = immunosuppression=20 (e.g., GVHD, systemic steroid use, or relapse of the underlying = disease=20 for which the transplant was performed) (AIII). Pediatric HSCT = recipients=20 and candidates should be supervised by adults during hand washing = to=20 ensure thorough cleaning (316) (BIII). Hand washing should = be=20 performed with an antimicrobial soap and water (AIII); = alternatively, use=20 of hygienic hand rubs is an acceptable means of maintaining hand = hygiene=20 (250,251). HSCT recipients who visit or live on farms = should follow=20 published recommendations for preventing cryptosporidiosis=20 (5,316,317--319) (BIII).=20
Preventing Respiratory Infections

To prevent respiratory infections after hospital discharge, = HSCT=20 recipients should observe the following precautions:=20

Frequent and thorough hand washing is critical (BIII), but = HSCT=20 recipients should also avoid touching their mucus membranes, = unless they=20 have washed their hands first, to avoid inoculating themselves = with CRV.=20
HSCT recipients should avoid close contact with persons with = respiratory illnesses (BIII). When close contact is unavoidable, = those=20 persons with respiratory illnesses should be encouraged to wash = their=20 hands frequently and to wear surgical masks or, at a minimum, = smother=20 their sneezes and coughs in disposable tissues. Alternatively, = the HSCT=20 recipient can wear a surgical mask (CIII).=20
HSCT recipients should avoid crowded areas (e.g., shopping = malls or=20 public elevators) where close contact with persons with = respiratory=20 illnesses is likely (BIII).=20
HSCT candidates or recipients should be advised that certain = activities and occupations (e.g., work in health-care settings, = prisons,=20 jails, or homeless shelters) can increase their risk for TB = exposure=20 (BIII). In deciding whether a patient should continue activities = in=20 these settings, physicians should evaluate the patient's = specific=20 duties, the precautions used to prevent TB exposure in the = workplace,=20 and the prevalence of TB in the community. The decision to = continue or=20 terminate such activities should be made jointly between patient = and=20 physician (BIII). HSCT recipients should avoid exposure to = persons with=20 active tuberculosis, particularly during the first 6 months = after HSCT=20 and during other periods of substantial immunosuppression (e.g., = GVHD,=20 systemic steroid use, or relapse of the underlying disease for = which the=20 transplant was performed) (BIII).

Researchers report that allogeneic recipients should avoid = construction=20 or excavation sites or other dust-laden environments for the first = 6=20 months after HSCT and during other periods of substantial=20 immunosuppression (e.g., GVHD, systemic steroid use, or relapse of = the=20 underlying disease for which the transplant was performed) to = avoid=20 exposures to molds (CIII). Researchers also report that outpatient = HSCT=20 recipients should be advised of travel routes to the HSCT center = that will=20 avoid or minimize exposure to construction sites (CIII).

Coccidioidomycosis is uncommon after allogeneic HSCT; however,=20 researchers report that HSCT recipients traveling to or residing = in=20 coccidioidomycosis-endemic areas (e.g., the American southwest, = Mexico,=20 and Central and South America) should avoid or minimize exposure = to=20 disturbed soil, including construction or excavation sites, areas = with=20 recent earthquakes, farms, or other rural areas (CIII). = Histoplasmosis=20 (Histoplasma capsulatum) after allogeneic HSCT is also = rare;=20 however, researchers report that HSCT recipients in = histoplasmosis-endemic=20 areas should avoid exposure to chicken coops and other = bird-roosting sites=20 and caves for the first 6 months after HSCT and during periods of=20 substantial immunosuppression (e.g., GVHD, systemic steroid use, = or=20 relapse of the underlying disease for which the transplant was = performed)=20 (CIII).

Smoking tobacco and exposure to environmental tobacco smoke are = risk=20 factors for bacterial and CRV infections among healthy adults and = children=20 (320--325); consequently, logic dictates that physicians = advise=20 HSCT recipients not to smoke and to avoid exposure to = environmental=20 tobacco smoke (CIII). However, no data were found that = specifically assess=20 whether smoking or environmental smoke exposure are risk factors = for OIs=20 among HSCT recipients. Researchers have reported that marijuana = smoking=20 might be associated with generation of invasive pulmonary = aspergillosis=20 among immunocompromised persons, including HSCT recipients=20 (326--329). Therefore, HSCT recipients should refrain from = smoking=20 marijuana to avoid Aspergillusspecies exposure=20 (326,330--334) (BIII).

Preventing Infections Transmitted Through Direct Contact = and=20 Respiratory Transmission

Researchers have proposed that immunocompromised HSCT = recipients and=20 candidates who are undergoing conditioning therapy avoid gardening = or=20 direct contact with soil, plants, or their aerosols to reduce = exposure to=20 potential pathogens (e.g., To. gondii, Hi. = capsulatum,=20 Cryptococcus neoformans, Nocardia species, and=20 Aspergillus species) (CIII). HSCT recipients, particularly=20 allogeneic recipients, could wear gloves while gardening or = touching=20 plants or soil (335) (CIII), and they should avoid creating = plant=20 or soil aerosols (BIII). Additionally, they should always wash = their hands=20 afterwards (335) and care for skin abrasions or cuts = sustained=20 during soil or plant contact (AIII).

Persons whose occupations involve animal contact (e.g., = veterinarians,=20 pet store employees, farmers, or slaughterhouse workers) could be = at=20 increased risk for toxoplasmosis and other zoonotic diseases. = Although=20 data are insufficient to justify a general recommendation against = HSCT=20 recipients working in such settings, these exposures should be = avoided=20 during the first 6 months after HSCT and during other periods of=20 substantial immunosuppression (e.g., GVHD, systemic steroid use, = or=20 relapse of the underlying disease for which the transplant was = performed)=20 (BIII).

Safe Sex

Sexually active HSCT recipients should avoid sexual practices = that=20 could result in oral exposure to feces (5,316) (AIII). = Sexually=20 active patients who are not in long-term monogamous relationships = should=20 always use latex condoms during sexual contact to reduce their = risk for=20 exposure to CMV, HSV, HIV, hepatitis B and C, and other sexually=20 transmitted pathogens (AII). However, even long-time monogamous = partners=20 can be discordant for these infections. Therefore, during periods = of=20 immunocompromise, sexually active HSCT recipients in such = relationships=20 should consider using latex condoms during sexual contact to = reduce the=20 risk for exposure to these sexually transmitted infections (CIII). =

Pet Safety

Preventing Pet-Transmitted Zoonotic Infections =

HSCT physicians should advise recipients and candidates = undergoing=20 conditioning therapy of the potential infection risks posed by pet = ownership; however, they should not routinely advise HSCT = recipients to=20 part with their pets, with limited exceptions. Generally,=20 immunocompromised HSCT recipients and candidates undergoing = conditioning=20 therapy should minimize direct contact with animals = (336,337),=20 particularly those animals that are ill (e.g., with diarrhea) = (335)=20 (BIII). Immunocompromised persons who choose to own pets should be = more=20 vigilant regarding maintenance of their pet's health than = immunocompetent=20 pet owners (BIII). This recommendation means seeking veterinary = care for=20 their pet early in the pet's illness to minimize the possible = transmission=20 of the pet's illness to the owner (335) (BIII). Feeding = pets only=20 high-quality commercial pet foods reduces the possibility of = illness=20 caused by spoiled or contaminated foods, thus reducing the = possibility of=20 transmitting illness from the pet to the HSCT recipient. If eggs, = poultry,=20 or meat products are given to the pet as supplements, they should = be=20 well-cooked. Any dairy products given to pets should be = pasteurized=20 (335) (BIII). Pets should be prevented from drinking toilet = bowl=20 water and from having access to garbage; pets should not scavenge, = hunt,=20 or eat other animals' feces (335) (BIII).

If HSCT recipients have contact with pets or animals, they = should wash=20 their hands after handling them (particularly before eating) and = after=20 cleaning cages; HSCT recipients should avoid contact with animal = feces to=20 reduce the risk for toxoplasmosis, cryptosporidiosis, = salmonellosis, and=20 campylobacteriosis (335) (BIII). Adults should supervise = hand=20 washing of pediatric HSCT recipients (BIII). Immunocompromised = HSCT=20 recipients and candidates should not clean pet litter boxes or = cages or=20 dispose of animal waste (DIII). If this cannot be avoided, = patients should=20 wear disposable gloves during such activities and wash their hands = thoroughly afterwards (BIII). Immunocompromised HSCT recipients = and=20 candidates should avoid adopting ill or juvenile pets (e.g., aged = <6=20 months for cats) (335) and any stray animals (5,316) = (BIII).=20 Any pet that experiences diarrhea should be checked by a = veterinarian for=20 infection with Cryptosporidium (5,316), = Giardia=20 species (335), Salmonella, and Campylobacter=20 (5,335,337) (BIII).

Immunocompromised HSCT recipients and candidates should not = have=20 contact with reptiles (e.g., snakes, lizards, turtles, or iguanas) = (DII)=20 to reduce their risk for acquiring salmonellosis = (335,338--341).=20 Additionally, patients should be informed that salmonellosis can = occur=20 from fomite contact alone (342). Therefore, HSCT recipients = and=20 candidates should avoid contact with a reptile, its food, or = anything that=20 it has touched, and if such contact occurs, recipients and = candidates=20 should wash their hands thoroughly afterwards (AIII). = Immunocompromised=20 HSCT recipients and candidates should avoid contact with ducklings = and=20 chicks because of the risk for acquiring Salmonella or=20 Campylobacter species infections (338,343) (BIII).=20 Immunocompromised HSCT recipients and candidates should avoid = contact with=20 exotic pets (e.g., nonhuman primates) (BIII). Bird cage linings = should be=20 cleaned regularly (e.g., daily) (337). All persons, but=20 particularly immunocompromised HSCT candidates and recipients, = should wear=20 gloves whenever handling items contaminated with bird droppings=20 (337) (BIII) because droppings can be a source of = Cryptococcus=20 neoformans, Mycobacterium avium, or Hi. = capsulatum.=20 However, routine screening of healthy birds for these diseases is = not=20 recommended (335) (DIII). To minimize potential exposure to = Mycobacterium marinum, immunocompromised HSCT recipients = and=20 candidates should not clean fish tanks (DIII). If this task cannot = be=20 avoided, patients should wear disposable gloves during such = activities and=20 wash their hands thoroughly afterwards (335,337) (BIII). =

Preventing Toxoplasmosis

The majority of toxoplasmosis cases in the United States is = acquired=20 through eating undercooked meat (335,337). However, all = HSCT=20 recipients and candidates, particularly those who are To. = gondii=20 seronegative, should be informed of the risks for contracting=20 toxoplasmosis from cat feces (BIII), but need not be advised to = give away=20 their cats (DII). For households with cats, litter boxes should = not be=20 placed in kitchens, dining rooms, or other areas where food = preparation=20 and eating occur (335). Additionally, litter boxes should = be=20 cleaned daily by someone other than the HSCT recipient during the = first 6=20 months after HSCT and during periods of substantial = immunosuppression=20 (e.g., GVHD, steroid use, or relapse of the underlying disease for = which=20 the transplant was performed) to reduce the risk for transmitting=20 toxoplasmosis to the HSCT recipient (BIII). Daily litter box = changes will=20 minimize the risk for fecal transmission of To. gondii = oocysts,=20 because fecal oocysts require >2 days of incubation to = become=20 infectious. If HSCT recipients perform this task during the first = 6 months=20 after HSCT and during subsequent periods of substantial = immunocompromise=20 (e.g., during GVHD, systemic steroid use, or relapse of the = underlying=20 neoplastic disease for which the transplant was performed), they = should=20 wear disposable gloves (335). Gloves should be discarded = after a=20 single use (BIII). Soiled, dried litter should be disposed of = carefully to=20 prevent aerosolizing the To. gondii oocysts (BIII). Cat = feces (but=20 not litter) can be flushed down the toilet (BIII). Also, persons = who clean=20 cat litter, particularly HSCT recipients, should wash their hands=20 thoroughly with soap and water afterwards to reduce their risk for = acquiring toxoplasmosis (BIII).

HSCT recipients and candidates with cats should keep their cats = inside=20 (BIII) and should not adopt or handle stray cats (DIII). Cats = should be=20 fed only canned or dried commercial food or well-cooked table = food, not=20 raw or undercooked meats, to eliminate the possibility of causing = an=20 illness that could be transmitted from the cat to the HSCT = recipient=20 (BIII). Pet cats of HSCT recipients do not need to be tested for=20 toxo-plasmosis (EII). Playground sandboxes should be kept covered = when not=20 in use to prevent cats from soiling them (BIII). HSCT recipients = and=20 candidates undergoing conditioning therapy should avoid drinking = raw=20 goat's milk to decrease the risk for acquiring toxoplasmosis = (BIII).

Water and Other Beverage Safety

Although limited data were found regarding the risks for and=20 epidemiology of Cryptosporidium disease among HSCT = recipients, HSCT=20 recipients are prudent to avoid possible exposures to=20 Cryptosporidium (BIII) because it has been reported to = cause=20 severe, chronic diarrhea, malnutrition, and death among other=20 immunocompromised persons (5,318,319). HSCT recipients = should avoid=20 walking, wading, swimming, or playing in recreational water (e.g., = ponds=20 or lakes) that is likely to be contaminated with = Cryptosporidium,=20 Es. coli O157:H7 (344--346), sewage, or animal or = human=20 waste (BII). HSCT recipients should also avoid swallowing such = water=20 (e.g., while swimming) (5,344,346) as well as any water = taken=20 directly from rivers and lakes (5,316) (AIII).

HSCT recipients should not use well water from private wells or = from=20 public wells in communities with limited populations (DIII) = because tests=20 for microbial contamination are performed too infrequently (e.g., = in=20 certain locations, tests are performed <1 times/month) = to detect=20 sporadic bacterial contamination. However, drinking well water = from=20 municipal wells serving highly populated areas is regarded as safe = from=20 bacterial contamination because the water is tested >2 = times/day=20 for bacterial contamination. If HSCT recipients consume tap water, = they=20 should routinely monitor mass media (e.g., radio, television, or=20 newspapers) in their area to immediately implement any boil-water=20 advisories that might be issued for immunocompromised persons by = state or=20 local governments (BIII). A boil-water advisory means that all tap = water=20 should be boiled for >1 minutes before it is consumed. = Tap water=20 might not be completely free of Cryptosporidium. To = eliminate the=20 risk for Cryptosporidium exposure from tap water, HSCT = recipients=20 can boil tap water for >1 minutes before consuming it = (e.g.,=20 drinking or brushing teeth) (5) (CIII). Alternately, they = can use=20 certain types of water filters (316) or a home distiller=20 (317) to reduce their risk for Cryptosporidium = (5)=20 and other waterborne pathogens (CIII). If a home water = filter******* is=20 used, it should be capable of removing particles >1 =B5m = in=20 diameter, or filter by reverse osmosis. However, the majority of = these=20 filters are not capable of removing smaller microbes (e.g., = bacteria or=20 viruses), and therefore, should only be used on properly treated = municipal=20 water. Further, the majority of these devices would not be = appropriate for=20 use on an unchlorinated private well to control viral or bacterial = pathogens. Bottled water can be consumed if it has been processed = to=20 remove Cryptosporidium by one of three processes --- = reverse=20 osmosis, distillation, or 1-=B5m particulate absolute filtration. = To confirm=20 that a specific bottled water has undergone one of these = processes, HSCT=20 recipients should contact the bottler directly.******** Patients = can take=20 other precautions in the absence of boil-water advisories to = further=20 reduce their risk for cryptosporidiosis. These extra precautions = include=20 avoiding fountain beverages and ice made from tap water at = restaurants,=20 bars, and theaters (5), fruit drinks made from frozen = concentrate=20 mixed with tap water, and iced tea or coffee made with tap water=20 (317). Drinks that are likely to be Cryptosporidium = safe for=20 HSCT recipients include nationally distributed brands of bottled = or canned=20 carbonated soft drinks and beers (5); commercially packaged = noncarbonated drinks that contain fruit juice; fruit juices that = do not=20 require refrigeration until after opening (e.g., those that are = stored=20 unrefrigerated on grocery shelves) (5); canned or bottled = soda,=20 seltzer or fruit drinks; steaming hot (>175 F) tea or = coffee=20 (317); juices labeled as pasteurized; and nationally = distributed=20 brands of frozen fruit juice concentrate that are reconstituted = with water=20 from a safe source (5). HSCT recipients should not drink=20 unpasteurized milk or fruit or vegetable juices (e.g., apple cider = or=20 orange juice) to avoid infection with Brucella species, = Es.=20 coli O157:H7, Salmonella species, = Cryptosporidium, and=20 others (319,347--351) (DII).

Food Safety

HSCT candidates and household or family members who prepare = food for=20 them after HSCT should review food safety practices that are = appropriate=20 for all persons (352) (AIII), and food preparers should be = educated=20 regarding additional food safety practices appropriate for HSCT=20 recipients. This review and education should be done before the=20 conditioning regimen (i.e., chemotherapy and radiation) begins = (BIII).=20 Adherence to these guidelines will decrease the risk for foodborne = disease=20 among HSCT recipients.

Food Safety Practices Appropriate for All Persons =

Raw poultry, meats, fish, and seafood should be handled on = separate=20 surfaces (e.g., cutting board or counter top) from other food = items. Food=20 preparers should always use separate cutting boards (i.e., one for = poultry=20 and other meats and one for vegetables and remaining cutting or = carving=20 tasks) (AIII), or the board(s) should be washed with warm water = and soap=20 between cutting different food items (AIII). To prevent foodborne=20 illnesses caused by Campylobacter jejuni and Salmonella=20 enteritidis, which can cause severe and invasive infections = among=20 immunocompromised persons (353,354), uncooked meats should = not come=20 in contact with other foods (BIII).

After preparing raw poultry, meats, fish, and seafood and = before=20 preparing other foods, food handlers should wash their hands = thoroughly in=20 warm, soapy water. Any cutting boards, counters, knives, and other = utensils used should be washed thoroughly in warm, soapy water = also=20 (AIII). Food preparers should keep shelves, counter tops, = refrigerators,=20 freezers, utensils, sponges, towels, and other kitchen items clean = (AIII).=20 All fresh produce should be washed thoroughly under running water = before=20 serving (355) (AIII). Persons preparing food should follow=20 published U.S. Department of Agriculture recommendations regarding = safe=20 food thawing (356) (BIII).

Persons cooking food for HSCT recipients should follow = established=20 guidelines for monitoring internal cooking temperatures for meats=20 (357) (AII). The only method for determining whether the = meat has=20 been adequately cooked is to measure its internal temperature with = a=20 thermometer because the color of the meat after cooking does not = reliably=20 reflect the internal temperature. Different kinds of meat should = be cooked=20 to varying internal temperatures, all >150 F (AII).=20 Specifically, the U.S. Department of Agriculture recommends that = poultry=20 be cooked to an internal temperature of 180 F; other meats and=20 egg-containing casseroles and souffles should be cooked to an = internal tem=20 perature of >160 F. Cold foods should be stored at = <40 F; hot=20 foods should be kept at >140 F (BIII). Food preparers should=20

wash their hands before and after handling leftovers (AIII); =
use clean utensils and food-preparation surfaces (AIII);=20
divide leftovers into small units and store in shallow = containers=20 for quick cooling (AII);=20
refrigerate leftovers within 2 hours of cooking (AII).=20
discard leftovers that were kept at room temperature for = >2 hours=20 (AIII);=20
reheat leftovers or heat partially cooked foods to = >165 F=20 throughout before serving (AII);=20
bring leftover soups, sauces, and gravies to a rolling boil = before=20 serving (AIII); and=20
follow published guidelines for cold storage of food = (352)=20 (AII).

Additional Food Safety Practices Appropriate for HSCT=20 Recipients

HSCT recipients' diets should be restricted to decrease the = risk for=20 exposure to foodborne infections from bacteria, yeasts, molds, = viruses,=20 and parasites (BIII). Currently, a low microbial diet is = recommended for=20 HSCT recipients (358,359) (BIII). This diet should be = continued for=20 3 months after HSCT for autologous recipients. Allogeneic = recipients=20 should remain on the diet until all immunosuppressive drugs (e.g., = cyclosporine, steroids, and tacrolimus) are discontinued. However, = the=20 HSCT physician should have final responsibility for determining = when the=20 diet can be discontinued safely. Only one study has reported that = dietary=20 changes (e.g., consuming yogurt) have decreased the risk for = mycotic=20 infections (e.g., candidal vaginitis) (360) (Table= =20 3). HSCT recipients should not eat any raw or undercooked = meat,=20 including beef, poultry, pork, lamb, venison or other wild game, = or=20 combination dishes containing raw or undercooked meats or = sweetbreads from=20 these animals (e.g., sausages or casseroles) (AII). Also, HSCT = recipients=20 should not consume raw or undercooked eggs or foods that might = contain=20 them (e.g., certain preparations of hollandaise sauce, Caesar and = other=20 salad dressings, homemade mayonnaise, and homemade eggnog) because = of the=20 risk for infection with Salmonella enteritidis (354) = (AII).=20 HSCT recipients should not consume raw or undercooked seafood = (e.g.,=20 oysters or clams) to prevent exposure to Vibrio species, = viral=20 gastroenteritis, and Cryptosporidium parvum = (361--364)=20 (AII).

HSCT recipients and candidates should only consume meat that is = welldone when they or their caretakers do not have direct control = over=20 food preparation (e.g., when eating in a restaurant) (AI). To = date, no=20 evidence exists in the United States that eating food at a fast = food=20 restaurant is riskier than eating at a conventional sit-down = restaurant.=20 Generally, HSCT candidates undergoing conditioning therapy and = HSCT=20 recipients with neutropenia (i.e., ANC < 1,000/ml³), = GVHD,=20 or immunosuppression should avoid exposures to naturopathic = medicines that=20 might contain molds (365) (DIII). HSCT recipients wishing = to take=20 naturopathic medications are advised to use them only as = prescribed by a=20 licensed naturopathic physician working in consultation with the=20 recipient's transplant and infectious disease physicians (CIII). =

Travel Safety

Travel to developing countries can pose substantial risks for = exposure=20 to opportunistic pathogens for HSCT recipients, particularly = allogeneic=20 recipients chronically immunosuppressed. HSCT recipients should = not plan=20 travel to developing countries without consulting their physicians = (AIII),=20 and travel should not occur until the period of severe = immunosuppression=20 has resolved. Generally, allogeneic recipients should not plan = travel to=20 developing countries for 6--12 months after HSCT, particularly if = GVHD has=20 occurred. Autologous recipients can travel to developing countries = 3--6=20 months after HSCT if their physicians agree.

HSCT recipients should be informed regarding strategies to = minimize the=20 risk for acquiring foodborne and waterborne infections while = traveling.=20 They should obtain updated, detailed health information for = international=20 travelers from health organizations (366,367) (AIII). = Generally,=20 while traveling in developing countries, HSCT recipients should = avoid=20 consuming the following (BIII):=20

raw fruits and vegetables,=20
tap water or any potentially untreated or contaminated = water,=20
ice made from tap water or any potentially contaminated = water,=20
unpasteurized milk or any unpasteurized dairy products,=20
fresh fruit juices,=20
food and drinks from street vendors, and=20
raw or undercooked eggs.
Steaming hot foods, = fruits peeled=20 by oneself, bottled and canned processed drinks, and hot coffee or = tea are=20 probably safe (367,368). Travelers should plan for treating = their=20 drinking water while in developing countries. If bottled water is = not=20 available, boiling is the best method of making water safe. = However, if=20 boiling water is not feasible, the traveler should carry supplies = for=20 disinfecting water (e.g., commercially available iodine = disinfection=20 tablets or a portable water filter) (366,368).=20
Antimicrobial prophylaxis for traveler's diarrhea is not = recommended=20 routinely for HSCT recipients traveling to developing countries = (DIII)=20 because traveler's diarrhea is not known to be more frequent or = more=20 severe among immunocompromised hosts. However, HSCT physicians who = wish to=20 provide prophylaxis to HSCT recipients who are traveling can = prescribe a=20 fluoroquinolone (e.g., ciprofloxacin hydrochloride) or TMP-SMZ = (CIII),=20 although resistance to TMP-SMZ is now common and resistance to=20 fluoroquinolones is increasing in tropical areas (Appen= dix).=20 Researchers recommend using bismuth subsalicylate to prevent = traveler's=20 diarrhea among adults (366). However, no data were found = regarding=20 safety and efficacy among HSCT recipients, and salicylates are not = recommended for use among persons aged <18 years because = salicylates=20 are associated with Reye's syndrome (369).

HSCT recipients' immunization status should be assessed and = their=20 vaccinations updated as needed before travel (366). = Influenza=20 chemoprophylaxis with rimantadine or amantadine can be used for=20 immunocompromised HSCT recipients who are traveling outside the=20 continental United States and who could be exposed to influenza A = (CIII).=20
HSCT RECIPIENT VACCINATIONS

Antibody titers to vaccine-preventable diseases (e.g., tetanus, = polio,=20 measles, mumps, rubella, and encapsulated organisms) decline = during the=20 1--4 years after allogeneic or autologous HSCT = (66,370--373) if the=20 recipient is not revaccinated. Clinical relevance of decreased = antibodies=20 to vaccine-preventable diseases among HSCT recipients is not = immediately=20 apparent because a limited number of cases of vaccine-preventable = diseases=20 are reported among U.S. recipients. However, vaccine-preventable = diseases=20 still pose risks to the U.S. population. Additionally, evidence = exists=20 that certain vaccine-preventable diseases (e.g., encapsulated = organisms)=20 can pose increased risk for HSCT recipients (66); = therefore, HSCT=20 recipients should be routinely revaccinated after HSCT so that = they can=20 experience immunity to the same vaccine-preventable diseases as = others (Table= =20 4).

HSCT center personnel have developed vaccination schedules for = HSCT=20 recipients (374). One study determined that HSCT center = personnel=20 used 3--11 different vaccination schedules per vaccine = (374);=20 consequently, the study authors requested national guidelines for = doses=20 and timing of vaccines after HSCT to eliminate confusion among = HSCT center=20 personnel regarding how to vaccinate their patients. To address = this need,=20 an interim vaccination schedule for HSCT recipients was drafted in = collaboration with partner organizations, including CDC's Advisory = Committee on Immunization Practices. The purpose of the = vaccination=20 schedule in these guidelines is to provide guidance for HSCT = centers (Table= =20 4). Although limited data were found regarding safety and=20 immunogenicity (e.g., serologic studies of antibody titers after=20 vaccination) among HSCT recipients, no data were found regarding = vaccine=20 efficacy among HSCT recipients (e.g., which determine whether = vaccinated=20 HSCT recipients have decreased attack rates of disease compared = with=20 unvaccinated HSCT recipients). Because certain HSCT recipients = have faster=20 immune system recovery after HSCT than others, researchers have = proposed=20 that different vaccination schedules be recommended for recipients = of=20 different types of HSCT. However, to date, data are too limited to = do so.=20 Therefore, the same vaccination schedule is recommended for all = HSCT=20 recipients (e.g., allogeneic, autologous, and bone marrow, = peripheral, or=20 UCB grafts) until additional data are published. In the tables, = vaccines=20 have only been recommended for use among HSCT recipients if = evidence=20 exists of safety and immunogenicity for those recipients. = Vaccination of=20 family members, household contacts, and HCWs are also recommended = to=20 minimize exposure of vaccine-preventable diseases among HSCT = recipients=20 (Table= s=20 5--8= ).=20
HEMATOPOIETIC STEM CELL SAFETY

With allogeneic HSCT, the life of the recipient might depend on = the=20 timely selection of an acceptable HLA-matched donor. Only a = limited number=20 of HLA-matched donors might be identified; hence, the transplant = physician=20 often has to accept a higher risk for transmission of an = infectious agent=20 through HSCT than would be permitted for routine blood = transfusion. This=20 section provides strategies for the HSCT physician to minimize=20 transmission of infectious diseases, whenever possible, from = donors to=20 recipients.********* ********** Whether to select a donor who is = at risk=20 for or who has an infectious disease transmissible by HSCT, should = be=20 determined on a case-by-case basis (AIII) and is the final = responsibility=20 of the HSCT physician (AIII). If the only possible donor is at = risk for or=20 known to be infected with a bloodborne pathogen and the patient is = likely=20 to succumb rapidly from his or her disease if an HSCT is not = received, the=20 physician must carefully weigh the risks and benefits of using = potentially=20 infected donor cells. No person should be denied a potentially = life-saving=20 HSCT procedure solely on the basis of the risk for an infectious = disease.=20 However, HSCT physicians should avoid transplanting any infected = or=20 infectious donor hematopoietic stem cell product unless no other = stem cell=20 product can be obtained and the risk for death from not undergoing = transplantation is deemed to be greater than the risk for = morbidity or=20 death from the infection that could potentially be transmitted = (DII). If=20 such a product is selected for use, it should be done on a = case-by-case=20 basis (375) and the following should be noted in the = recipient's=20 chart:=20

knowledge and authorization of the recipient's HSCT = physician=20 regarding the potential for transmission of an infectious agent = during=20 HSCT, and=20
advance informed consent from the recipient or recipient's = legal=20 guardian acknowledging the possible transmission of an = infectious agent=20 during the transplantation (AIII).
Subsequently, the = HSCT=20 physician should include the infectious agent in the differential=20 diagnosis of any illness that the HSCT recipient experiences so = that the=20 infection, if transmitted, can be diagnosed early and treated=20 preemptively, if possible. Infectious products (except those in = which CMV=20 seropositivity is the only evidence of infectiousness) should be = labeled=20 as being a biohazard or as untested for biohazards, as applicable. = Tissue=20 intended for autologous use should be labeled "For Autologous Use = Only ---=20 Use Only for (Patient's Name)."=20
Preventing Transmission of Infections from HSCT Donors to=20 Recipients

All prospective HSCT donors should be evaluated through a = physical=20 history and examination to determine their general state of health = and=20 whether they pose a risk for transmitting infectious diseases to = the=20 recipient (376). To detect transmissible infections, all = HSCT donor=20 collection site personnel should follow up-to-date published = guidelines=20 and standards for donor screening (e.g., medical history), = physical exam,=20 and serologic testing (377--383) (AIII). Initial donor = screening=20 and physical exam should be performed <8 weeks before = the=20 planned donation (BIII). Donor serologic testing should be done=20 <30 days before donation to detect potentially = transmissible=20 infections (BII); additionally, researchers recommend that donors = be=20 retested <7 days before collection. If testing is done = >7=20 days before donation, donor screening should be repeated to ensure = that no=20 new risk behaviors have occurred during the interval between the = original=20 screening and the time of donation (BIII). This practice is = critical=20 because if new behavioral risk factors have occurred, the = potential donor=20 might need to be deferred. Screening and testing should be done on = all=20 allogeneic or syngeneic donors (AIII). Screening and testing of = autologous=20 donors is recommended to ensure the safety of laboratory personnel = and to=20 prevent cross contamination (BIII). If autologous donors are not = tested,=20 their autologous units should be specially labeled and handled as = if=20 potentially infected (BIII). For donors screened in the United = States,=20 FDA-licensed or -approved tests should be used in accordance with = the=20 manufacturers' instructions (AIII), and the donor samples should = be tested=20 in laboratories certified by the Clinical Laboratory Improvement=20 Amendments of 1988 (AIII).

All HSCT donors should be in good general health (376) = (BIII).=20 Acute or chronic illness in the prospective donor should be = investigated=20 to determine the etiology. Generally, persons who are ill should = not be=20 HSCT donors (DIII). A flu-like illness in a prospective donor at = the time=20 of evaluation or between the time of evaluation and donation = should prompt=20 evaluation of and serologic testing for infections that might pose = a risk=20 to the recipient (e.g., EBV, CMV, To. gondii) (BIII). = Persons with=20 a positive serum EBV-viral capsid antigen IgM but negative serum = EBV-viral=20 capsid antigen IgG should not serve as donors for allogeneic=20 T-cell--depleted HSCT, particularly for unrelated or mismatched=20 transplants, until their serum EBV-viral capsid antigen IgG = becomes=20 positive (DIII). Persons with acute toxoplasmosis should not = donate until=20 the acute illness has resolved (DII); however, physicians should = be aware=20 that persons who are asymptomatically seropositive for To. = gondii=20 might transmit this infection through HSCT (218).

Prospective donors with symptoms of active TB should be = evaluated for=20 that disease (383) (BIII). Prospective donors with active = TB should=20 not donate (EIII) until the TB is well-controlled (e.g., no longer = contagious as determined by the donor's primary physician) after=20 appropriate medical therapy. However, no known risk exists from=20 transplanting marrow from an untreated, tuberculin-positive donor = who has=20 no evidence of active disease. Screening potential donors for TB = with=20 Mantoux skin tests (DIII) is not necessary. Prospective HSCT = donors who=20 reside in or have traveled to areas endemic for rickettsia or = other=20 tickborne pathogens and who are suspected of having an acute = tickborne=20 infection should be temporarily deferred as donors until infection = with=20 these pathogens is excluded (DIII). Relevant pathogens include=20 Rickettsia rickettsii, Babesia microti and other=20 Babesia species, Coxiella burnetii, and the Colorado = tick=20 fever virus, which are the etiologic agents of Rocky Mountain = spotted=20 fever, babesiosis, Q fever, and Colorado tick fever, respectively; = these=20 pathogens have been reported to be transmitted by blood = transfusion=20 (384--388). Researchers recommend deferral for a past = history of Q=20 fever or babesiosis because these infections can be chronic and = the=20 babesiosis parasite might persist despite appropriate therapy = (389)=20 (CIII). Additionally, researchers have recommended deferring = persons with=20 acute human ehrlichiosis (e.g., human active human granulocytic=20 ehrlichiosis [390], human monocytic ehrlichiosis, as well = as any=20 infections from Ehrlichia ewingii) from HSCT donation = (CIII).

The medical history of the prospective HSCT donor should = include the=20 following:=20

History of vaccinations (377) during the 4 weeks = before=20 donation (AII). If the potential donor is unsure of vaccinations = received, his or her records should be reviewed. HSCT donation = should be=20 deferred for 4 weeks after the donor receives any = live-attenuated=20 vaccine (e.g., rubeola [measles], mumps, rubella [German = measles], oral=20 polio, varicella, yellow fever, and oral typhoid vaccines) = (EIII). This=20 deferral will avoid the possibility of infusing a live = infectious agent=20 into an HSCT recipient. HSCT donation need not be deferred for = persons=20 who have recently received toxoid or killed (i.e., inactivated), = recombinant viral, bacterial, or rickettsial vaccines as long as = the=20 donor is asymptomatic and afebrile (389) (BIII). Such = vaccines=20 include tetanus toxoid, diphtheria toxoid, hepatitis A and B, = cholera,=20 influenza (i.e., killed intramuscular vaccine), meningococcal,=20 paratyphoid, pertussis, plague, polio (i.e., inactivated polio = vaccine),=20 rabies, typhoid (i.e., inactivated intramuscular vaccine), or = typhus=20 vaccines (389).=20
Travel history (BIII) to determine whether the donor has = ever=20 resided in or traveled to countries with endemic diseases that = might be=20 transmitted through HSCT (e.g., malaria). Permanent residents of = nonendemic countries who have traveled to an area that CDC = regards as=20 endemic for malaria can be accepted as HSCT donors if 1 year has = elapsed=20 since the donor's departure from the endemic area and if the = donor has=20 been free of malaria symptoms, regardless of whether he or she = received=20 antimalarial chemoprophylaxis. Because cases of HSCT-transmitted = malaria=20 have been reported (391,392), persons who have had = malaria and=20 received appropriate treatment should be deferred from HSCT = donation for=20 3 years after becoming asymptomatic. Immigrants, refugees, = citizens, or=20 residents for >5 years of endemic countries can be = accepted as=20 HSCT donors if 3 years have elapsed since they departed the = malarious=20 area and if they have been free of malaria symptoms.=20
History of Chagas' disease and leishmaniasis. Persons with = active=20 Chagas' disease or leishmaniasis should not serve as HSCT donors = (DIII)=20 because these diseases can be transmitted by transfusion=20 (227,229,231,393--395). Researchers also recommend = deferral of=20 HSCT donation if a past history exists of either of these = diseases=20 because the parasite can persist despite therapy = (227--229,231,=20 389,393--395) (CIII).=20
History of any deferral from plasma or blood donation. The = reason=20 for such a deferral (376) and whether it was based on a = reported=20 infectious disease or behavioral or other risk factor should be=20 investigated (BIII).=20
History of viral hepatitis. A person with a history of viral = hepatitis after his or her eleventh birthday should be excluded = from=20 HSCT donation (BIII).=20
History of blood product transfusion, solid organ = transplantation,=20 or transplantation of tissue within the last 12 months (BIII). = Such=20 persons should be excluded from HSCT donation (DIII). = Xenotransplant=20 product recipients and their close contacts should be = indefinitely=20 deferred from donating any blood products, including = hematopoietic stem=20 cells, whole blood, or other blood components including plasma,=20 leukocytes, and tissues (396) (AIII). Close contacts to = be=20 deferred from donations include persons who have engaged = repeatedly in=20 activities that could result in an intimate exchange of body = fluids with=20 a xenotransplantation product recipient. Such close contacts = could=20 include sexual partners, household members who share razors or=20 toothbrushes, and HCWs or laboratory personnel with repeated=20 percutaneous, mucosal, or other direct exposures.=20
History of risk factors for classic Creutzfeldt-Jakob = disease (CJD),=20 including any blood relative with Creutzfeldt-Jakob disease, = receipt of=20 a human pituitary-derived growth hormone or receipt of a corneal = or dura=20 mater graft (383,397--399) (BIII). Potential HSCT donors = should=20 also be screened for new variant Creutzfeldt-Jakob Disease = (nvCJD) risk=20 factors, including a history of cumulative travel or residence = in the=20 United Kingdom for >6 months during 1980--1996 or = receipt of=20 injectable bovine insulin since 1980, unless the product was not = manufactured since 1980 from cattle in the United Kingdom = (398)=20 (BIII). The clinical latency period for iatrogenic, classic CJD = can be=20 >30 years (398), and transmission of classic CJD by = blood=20 products is highly unlikely (398). Although no classic or = nvCJD=20 has ever been reported among HSCT recipients, persons with a = history of=20 classic or nvCJD risk factors should be excluded from donation = for=20 unrelated HSCT (DIII) if a choice exists between two otherwise = equally=20 suitable donors. The risk for transmitting classic or nvCJD from = an HSCT=20 donor to a recipient is unknown, but researchers believe that = persons=20 with nvCJD risk factors could be at higher risk for transmitting = nvCJD=20 to HSCT recipients than persons with classic CJD risk factors.=20
Past medical history that indicates the donor has clinical = evidence=20 of or is at high risk for acquiring a bloodborne infection = (e.g., HIV-1=20 or -2, human T-lymphotropic virus [HTLV]-I or -II, hepatitis C, = or=20 hepatitis B) (381,383), including=20

men who have had sex with another man during the preceding = 5 years=20 (381,383) (BIII);=20
persons who report nonmedical intravenous, intramuscular, = or=20 subcutaneous injection of drugs during the preceding 5 years=20 (381) (BIII);=20
persons with hemophilia or related clotting disorders who = have=20 received human-derived clotting factor concentrates = (381)=20 (BIII);=20
persons who have engaged in sex in exchange for money or = drugs=20 during the preceding 5 years (381) (BIII);=20
persons who have had sex during the preceding 12 months = with any=20 person described previously (381) or with a person = known or=20 suspected to have HIV (381) or hepatitis B infections = (BIII);=20
persons who have been exposed during the preceding 12 = months to=20 known or suspected HIV, hepatitis B- or C-infected blood = through=20 percutaneous inoculation or through contact with an open = wound,=20 nonintact skin, or mucous membrane (381) (BIII);=20
inmates of correctional systems (379--381) and = persons who=20 have been incarcerated for >72 consecutive hours during the = previous 12 months (BIII);=20
persons who have had or have been treated for syphilis or=20 gonorrhea during the preceding 12 months (376,379,380) = (BIII);=20 and=20
persons who within 12 months have undergone tattooing,=20 acupuncture, ear or body piercing (380,400,401) in = which shared=20 instruments are known to have been used (BIII) or other = nonsterile=20 conditions existed.
Persons reporting any = of these=20 past medical histories should be excluded from donation (DIII).=20
The following serologic tests should be performed for each = prospective=20 donor:=20

HIV-1 antigen, anti-HIV-1 and -2, anti-HTLV-I and -II, = hepatitis B=20 surface antigen, total antihepatitis B core antigen, = antihepatitis C,=20 anti-CMV, and a serologic test for syphilis = (376,379,380,383)=20 (AIII). Potential donors who have repeatedly reactive screening = tests=20 for HIV-1 antigen, anti-HIV-1 or -2, anti-HTLV-I or -II, = antihepatitis=20 C, hepatitis B surface antigen, or antihepatitis B core antigen = should=20 be excluded as HSCT donors (381) (EII). Persons who = refuse=20 infectious disease testing should also be excluded as HSCT = donors=20 (381) (EIII).=20
Investigational nucleic acid tests to detect hepatitis C = virus RNA=20 and HIV RNA are currently being used in the United States to = screen=20 blood donors and could be used for screening HSCT donors. If = nucleic=20 acid tests are approved by FDA, these tests should be = incorporated into=20 routine screening regimens for HSCT donors. When nucleic acid = testing is=20 done for HIV and hepatitis C investigationally, a positive = result should=20 exclude the potential donor.
All infectious disease = testing and=20 results should be reported to the HSCT physician before the = candidate's=20 conditioning regimen begins (381) (AIII). Bone marrow = should be=20 collected using sterile technique in a medically acceptable = setting and=20 according to standard operating procedures (AIII).=20
HSCT transplant center personnel should keep accurate records = of all=20 HSCT received and the disposition of each sample obtained = (381).=20 These tracking records must be separate from patients' medical = records=20 (e.g., in a log book) so that this information is easily = obtainable.=20 Recorded information should include the donor identification = number, name=20 of procurement of distribution center supplying the HSCT,=20 recipient-identifying information, name of recipient's physician, = and=20 dates of a) receipt by the HSCT center and b) either = transplantation to=20 the recipient or further distribution (381) (AIII). All = centers for=20 donation, transplantation, or collection of hematopoietic stem = cells=20 should keep records of donor screening and testing, and HSCT = harvesting,=20 processing, testing, cryopreservation, storage, and infusion or = disposal=20 of each aliquot of donated hematopoietic progenitor cells for=20 >10 years after the date of implantation, = transplantation,=20 infusion, or transfer of the product (378) (AIII). However, = if that=20 date is not known, records should be retained >10 years = after=20 the product's distribution, disposition, or expiration, whichever = is=20 latest.

Pediatric Donors

Children aged >18 months who are born to mothers with or at = risk for=20 HIV infection, who have not been breast-fed during the past 12 = months, and=20 whose HIV antibody tests, physical examination, and medical = records do not=20 indicate evidence of HIV infection can be accepted as donors = (381)=20 (BIII). Children aged <18 months who are born to mothers with = or at=20 risk for HIV infection and who have not been breast-fed by an = HIV-infected=20 woman during the past 12 months can be accepted as donors only if = HIV=20 infection has been excluded according to established criteria = (402)=20 (BIII). Children who have been breast-fed by an HIV-infected woman = during=20 the past 12 months should be excluded as stem cell donors = regardless of=20 HIV infection status (AIII). The mother and, if possible, the = father of=20 all pediatric stem-cell donors who are at risk for perinatal = transmission=20 of HIV and other bloodborne infections, should be interviewed by a = health-care professional competent to elicit information regarding = risk=20 factors for possible bloodborne infection in the potential = pediatric donor=20 (AIII). Children who meet any of the adult donor exclusion = criteria should=20 not become HSCT donors (381) (EIII).

Preventing Infection from Extraneous Contamination of = Donated=20 Units

Personnel of donation, collection, or transplantation centers,=20 cell-processing laboratories, and courier services should follow = current=20 standards for detecting and preventing extrinsic bacterial and = fungal=20 contamination of collected stem cell units at the collection site, = during=20 processing and transportation, and at the transplant center = (376)=20 (AIII). Quality improvement programs and procedure manuals of = collection=20 centers, cell-processing laboratories, and transplant programs = should=20 include strategies for preventing transplant-associated = infections. For=20 example, collection centers should use aseptic techniques when = collecting=20 marrow, peripheral blood, and UCB hematopoietic stem cells=20 (376,378) (AIII). Whenever possible, closed systems should = be used=20 for pooling hematopoietic stem cells during a collection procedure = (BIII)=20 because higher rates of microbial contamination seen in marrow = harvests=20 versus blood stem cell collections can be caused by use of open = collecting=20 systems (375,403,404). The highest risk for extraneous = microbial=20 contamination of hematopoietic stem cells occurs during extensive=20 manipulation and processing in the laboratory (404,405). = Potential=20 sources include unprotected hands and laboratory equipment and = freezers=20 (406), particularly the liquid phases of liquid nitrogen = freezers=20 (407). Therefore, stem cell processing should be performed=20 according to current standards (378) using approved = manufacturing=20 practices (AIII). Hematopoietic stem cell units thawed in a water = bath=20 should be enclosed in a second bag (i.e., double-bagged technique) = to=20 prevent contamination of the ports or caps from unsterile bath = water=20 (407) (BIII). Additionally, water baths should be cleaned = routinely=20 (BIII) and certain researchers have proposed that the bath contain = sterile=20 water (407) (CIII). Researchers also report sterilizing = liquid=20 nitrogen freezers before initial use for hematopoietic stem cell = storage=20 (407) until fungal and bacterial cultures are negative = (CIII).

Cell-processing laboratory personnel should implement programs = to=20 detect extrinsic bacterial or fungal contamination of collected = stem cell=20 units, ideally before transplantation (AIII). Although repeated = cultures=20 are costly (408), donated hematopoietic stem cells should = be=20 cultured for aerobic bacteria and fungi >1 times during = initial=20 processing and freezing (BIII). Researchers also have proposed = adding=20 anaerobic bacterial cultures and culturing twice, once at the end = of=20 processing, and once after thawing just before use (407) = (CIII). If=20 bacterial culture results are positive, antibiotic-susceptibility = tests=20 should be performed (BIII). Results of cultures and=20 antibiotic-susceptibility tests should be provided to the = transplant=20 physician before release of a cryopreserved marrow or blood stem = cell=20 unit, and as soon as feasible for transplants infused before = completion of=20 culture incubation (BIII).

Collection center, cell-processing laboratory, and transplant = program=20 personnel should maintain active surveillance of infections among = persons=20 who have received hematopoietic stem cells from those facilities = to=20 collect data regarding the number of infections after HSCT that = might have=20 been caused by exogenous contamination of donor stem cells (BIII) = because=20 this type of infection has been reported (405).

In Utero or Fetal HSCT

No national standards exist for in utero or fetal HSCT, and the = overall=20 risks for transmitting infections to a fetus through HSCT = (409,410)=20 have not been determined. However, in addition to precautions = appropriate=20 for adult recipients, physicians performing in utero or fetal HSCT = are=20 advised to evaluate potential donors for evidence of active = infectious=20 diseases that could cause serious congenital infections (e.g., = rubella,=20 varicella, CMV, syphilis, or To. gondii) in the fetus = (CIII).=20
Acknowledgments

The authors gratefully acknowledge the assistance of the = following=20 persons in the preparation of this report: Jon S. Abramson, M.D.; = Saundra=20 N. Aker, R.D.; George J. Alangaden, M.D.; Ann Arvin, M.D.; Carol = Baker,=20 M.D.; Michael Boeckh, M.D.; Brian J. Bolwell, M.D.; John M. Boyce, = M.D.;=20 C. Dean Buckner, M.D.; Pranatharthi H. Chandrasekar, M.D.; D.W. = Chen,=20 M.D., M.P.H.; Joan Chesney, M.D.; Raymond Chinn, M.D.; Christina = Cicogna,=20 M.D.; Dennis Confer, M.D.; Stella M. Davies, M.D., Ph.D.; Alfred = DeMaria,=20 Jr., M.D.; David W. Denning, M.B.B.S.; Joseph Fay, M.D.; Stephen = Forman,=20 M.D.; Michael Gerber, M.D.; Anne A. Gershon, M.D.; Stuart L. = Goldberg,=20 M.D.; Marie Gourdeau, M.D.; Christine J. Hager, Ph.D.; Rebecca = Haley,=20 M.D.; Liana Harvath, Ph.D.; Kelly Henning, M.D.; Steve Heyse; = Elizabeth=20 Higgs; Kevin High, M.D.; Mary M. Horowitz, M.D.; Craig W.S. Howe, = M.D.,=20 Ph.D.; David D. Hurd, M.D.; Hakan Kuyu, M.D.; Amelia A. Langston, = M.D.;=20 Catherine Laughlin, Ph.D.; Hillard M. Lazarus, M.D.; Joseph H. = Laver,=20 M.D.; Helen Leather, Phar.D.; Paul R. McCurdy, M.D.; Carole = Miller, M.D.;=20 I. George Miller, M.D.; Per Ljungman, M.D., Ph.D.; Paul R. = McCurdy, M.D.;=20 Richard J. O'Reilly, M.D.; Gary Overturf, M.D.; Jan E. Patterson, = M.D.;=20 Lauren Patton, D.D.S.; Doug Peterson, D.D.S., Ph.D.; Donna = Przepiorka,=20 M.D., Ph.D.; Philip A. Pizzo, M.D.; Charles G. Prober, M.D.; Issam = Raad,=20 M.D.; Elizabeth C. Reed, M.D.; Frank Rhame, M.D.; Olle Ringd=E9n, = M.D.;=20 Stephen M. Rose, Ph.D.; Scott D. Rowley, M.D.; Pablo Rubinstein, = M.D.;=20 Martin Ruta; Joel Ruskin, M.D.; Thomas N. Saari, M.D.; Stephen = Schoenbaum,=20 M.D.; Mark Schubert, D.D.S., M.S.D.; Jane D. Siegel, M.D.; = Jacqueline=20 Sheridan; Alicia Siston, M.D.; Trudy N. Small, M.D.; Frank O. = Smith, M.D.;=20 Ruth Solomon, M.D.; Cladd Stevens, M.D.; Patrick J. Stiff, M.D.; = Andrew J.=20 Streifel, M.P.H.; Donna A. Wall, M.D.; Thomas Walsh, M.D.; Phyllis = Warkentin, M.D.; Robert A. Weinstein, M.D.; Estella Whimbey, M.D.; = Richard=20 Whitley, M.D.; Catherine Wilfert, M.D.; Drew J. Winston, M.D.; = Jeffrey=20 Wolf, M.D.; Andrew Yeager, M.D.; John A. Zaia, M.D.; and Carol = Zukerman.=20

Contributions from the following CDC staff are also gratefully=20 acknowledged: Larry J. Anderson, M.D.; Fred Angulo, D.V.M.; = Richard=20 Besser, M.D.; Jay C. Butler, M.D.; Donald Campbell; Mary E. = Chamberland,=20 M.D.; James Childs, Sc.D.; Nancy J. Cox, Ph.D.; Robert B. Craven, = M.D.;=20 Jackie Curlew; Vance J. Dietz, M.D., M.P.H.T.M.; Richard Facklam, = Ph.D.;=20 Cindy R. Friedman, M.D.; Keiji Fukuda, M.D., M.P.H.; Rana A. = Hajjeh, M.D.;=20 Barbara Herwaldt, M.D., M.P.H.; AnnMarie Jenkins; Dennis D. = Juranek,=20 D.V.M., M.Sc.; Paul Kilgore, M.D.; William Kohn, D.D.S.; Jacobus = Kool,=20 M.D., D.T.M.H.; John R. Livengood, M.D., M.Phil.; Eric Mast, M.D., = M.P.H.;=20 Michael McNeil, M.D., M.P.H.; Robin R. Moseley, M.A.T.; Thomas R. = Navin,=20 M.D.; Adelisa Panlilio, M.D., M.P.H.; Monica Parise, M.D.; Michele = Pearson, M.D.; Bradford A. Perkins, M.D.; Renee Ridzon, M.D.; = Martha=20 Rogers, M.D.; Nancy Rosenstein, M.D.; Charles Rupprecht, Ph.D., = V.M.D.;=20 Peter Schantz, Ph.D.; Lawrence B. Schonberger, M.D., M.P.H.; Jane = Seward,=20 M.B.B.S., M.P.H.; John A. Stewart, M.D.; Raymond Strikas, M.D.; = Robert V.=20 Tauxe, M.D., M.P.H.; Theodore Tsai, M.D.; Rodrigo Villar, M.D.; = David=20 Wallace; and Sherilyn Wainwright, D.V.M., M.D.

The contributions of staff from other federal and = nongovernmental=20 agencies are also gratefully acknowledged: Agency for Healthcare = Research=20 and Quality; Food and Drug Administration; Health Resources and = Services=20 Administration; National Institutes of Health; National Cancer = Institute;=20 National Heart, Lung, and Blood Institute; National Institute for = Allergy=20 and Infectious Diseases; CDC's Advisory Committee on Immunization=20 Practices; American Academy of Pediatrics' Committee on Infectious = Diseases; American Association of Blood Banks; Hospital Infection = Control=20 Advisory Committee; International Society of Hematotherapy and = Graft=20 Engineering; National Marrow Donor Program; Southwest Oncology = Group;=20 Foundation for the Accreditation of Hematopoietic Cell Therapy; = and=20 Society for Healthcare Epidemiology of America.

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Bacterial Infections

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Hammarstr=F6m V, Pauksen K, Azinge J, et al. Pneumococcal = immunity and=20 response to immunization with pneumococcal vaccine in bone = marrow=20 transplant patients: the influence of graft versus host = reaction.=20 Support Care Cancer 1993;1:195--9.=20
Guinan EC, Molrine DC, Antin JH, et al. Polysaccharide = conjugate=20 vaccine responses in bone marrow transplant patients. Transplant = 1994;57(5):677--84.=20
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Viral Infections

Bowden RA, Slichter SJ, Sayers M, et al. Comparison of = filtered=20 leukocyte-reduced and cytomegalovirus (CMV) seronegative blood = products=20 for the prevention of transfusion-associated CMV infection after = marrow=20 transplantation. Blood 1995;86(9):3598--603.=20
Boeckh M, Gooley TA, Myerson D, Cunningham T, Schoch G, = Bowden RA.=20 Cytomegalovirus pp65 antigenemia-guided early treatment with = ganciclovir=20 versus ganciclovir at engraftment after allogeneic marrow=20 transplantation: a randomized double blind study. Blood=20 1996;88(10):4063--71.=20
Boeckh M, Stevens-Ayers T, Bowden R. Cytomegalovirus pp65=20 antigenemia after autologous marrow and peripheral blood stem = cell=20 transplantation. J Infect Dis 1996;174(5):907--12.=20
Boeckh M, Bowden R. Cytomegalovirus infection in marrow=20 transplantation. In: Buckner CD, Clift RA, ed. Technical and = biological=20 components of marrow transplantation. Boston, MA: Kluwer = Academic=20 Publishers, 1995:97--136.=20
Einsele H, Ehninger G, Hebart H, et al. Polymerase chain = reaction=20 monitoring reduces the incidence of cytomegalovirus disease and = the=20 duration and side effect of antiviral therapy after bone marrow=20 transplantation. Blood 1995;86(7):2815--20.=20
Mendez JC, Sia IG, Paya CV. Human cytomegalovirus. In: = Lennette EH,=20 Smith TF, eds. Laboratory diagnosis of viral infections. = 3^rd=20 ed., revised and expanded. New York, NY: Marcel Decker, Inc., = 1999:=20 361--72.=20
Goodrich JM, Mori M, Gleaves CA, et al. Early treatment with = ganciclovir to prevent cytomegalovirus disease after allogeneic = bone=20 marrow transplant. N Engl J Med 1991;325(23):1601--7.=20
Schmidt GM, Horak DA, Niland JC, Duncan SR, Forman SJ, Zaia = JA.=20 Randomized controlled trial of prophylactic ganciclovir for=20 cytomegalovirus pulmonary infection in recipients of allogeneic = bone=20 marrow transplants. New Engl J Med 1991;324(15):1005--11.=20
Goodrich JM, Bowden RA, Fisher L, Keller C, Schoch G. Meyers = JD.=20 Ganciclovir prophylaxis to prevent cytomegalovirus disease after = allogeneic marrow transplant. Ann Intern Med 1993;118(3):173--8. =
Mazzulli T, Drew LW, Yen-Lieberman B, et al. Multicenter = comparison=20 of the Digene Hybrid Capture CMV DNA Assay (Version 2.0), the = pp65=20 antigenemia assay, and cell culture for the detection of = cytomegalovirus=20 viremia. J Clin Microbiol 1999;37(4):958--63.=20
Gerna G, Baldanti F, Middeldorp JM, et al. Clinical = significance of=20 expression of human cytomegalovirus pp67 late transcript in = heart, lung,=20 and bone marrow transplant recipients as determined by nucleic = acid=20 sequence-based amplification. J Clin Microbiol = 1999;37(4):902--11.=20
Singhal S, Mehta J, Powles R, et al. Three weeks of = ganciclovir for=20 cytomegalovirus after allogeneic bone marrow transplantation. = Bone=20 Marrow Transplant 1995;15(5):777--81.=20
Verdonck LF, Dekker AW, Rozenberg-Arska M, van den Hoek MR.=20 Risk-adapted approach with a short course of ganciclovir to = prevent=20 cytomegalovirus (CMV) pneumonia in CMV-seropositive recipients = of=20 allogeneic bone marrow transplants. Clin Infect Dis 1997;24(5): = 901--7.=20
Zaia J, Gallez-Hawkins GM, Longmate J, et al. Late bacterial = and=20 fungal sepsis and mortality after BMT are increased by duration = of early=20 ganciclovir preemptive therapy for CMV infection [Abstract = 2128]. Blood=20 1998;92(10)(suppl 1 [part 1 of 2]):518a.=20
Bacigalupo A, Bregante S, Tedone E, et al. Combined=20 foscarnet-ganciclovir treatment for cytomegalovirus infections = after=20 allogeneic hematopoietic stem cell transplantation. Transplant=20 1996;62(3);376--80.=20
Moretti S, Zikos P, Van Lint MT, et al. Foscarnet vs = ganciclovir for=20 cytomegalovirus (CMV) antigenemia after allogeneic hematopoietic = stem=20 cell transplantation (HSCT): a randomized study. Bone Marrow = Transplant=20 1998;22(2):175--80.=20
Boeckh M, Hoy C, Torok-Storb B. Occult cytomegalovirus = infection of=20 marrow stroma. Clin Infect Dis 1998;26(1):209--10.=20
Krause H, Hebart H, Jahn G, Muller CA, Einsele H. Screening = for=20 CMV-specific T-cell proliferation to identify patients at risk = of=20 developing late onset CMV disease. Bone Marrow Transplant=20 1997;19(11):1111--16.=20
Gor D, Sabin C, Prentice HG, et al. Longitudinal = fluctuations in=20 cytomegalovirus load in bone marrow transplant patients: = relationship=20 between peak virus load, donor/recipient serostatus, acute GVHD = and CMV=20 disease. Bone Marrow Transplant 1998;21(6):597--605.=20
Zaia JA, Gallez-Hawkins GM, Teftmeier BR, et al. Late=20 cytomegalovirus disease in marrow transplantation is predicted = by virus=20 load in plasma. J Infect Dis 1997;176(3):782--5.=20
Ljungman P, Aschan J, Azinge JN, et al. Cytomegalovirus = viremia and=20 specific T-helper cell responses as predictors of disease after=20 allogeneic marrow transplantation. Br J Haematol = 1993;83(1):118--24.=20
Lazzarotto T, Varani S, Spezzacatena P, et al. Delayed = acquisition=20 of high-avidity anti-cytomegalovirus antibody is correlated with = prolonged antigenemia in solid organ transplant recipients. J = Infect Dis=20 1998;178(4):1145--9.=20
Boeckh M, Gallez-Hawkins GM, Myerson D, Zaia JA, Bowden RA. = Plasma=20 polymerase chain reaction for cytomegalovirus DNA after = allogeneic=20 marrow transplantation: comparison with polymerase chain = reaction using=20 peripheral blood leukocytes, pp65 antigenemia, and viral = culture.=20 Transplant 1997;64(1):108--13.=20
Prentice HG, Gluckman E, Powles RL, et al. Impact of = long-term=20 acyclovir on cytomegalovirus infection and survival after = allogeneic=20 bone marrow transplantation. Lancet 1994;343(8900):749--53.=20
Boeckh M, Gooley TA, Bowden RA. Effect of high-dose = acyclovir on=20 survival in allogeneic marrow transplant recipients who received = ganciclovir at engraftment or for cytomegalovirus pp65 = antigenemia. J=20 Infect Dis 1998;178(4):1153--7.=20
Boeckh M, Gooley TA, Reusser P, Buckner CD, Bowden RA. = Failure of=20 high-dose acyclovir to prevent cytomegalovirus disease after = autologous=20 marrow transplantation. J Infect Dis 1995;172(4):939--43.=20
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Rooney CM, Smith CA, Ng CY, et al. Infusion of cytotoxic T = cells for=20 the prevention and treatment of Epstein-Barr virus-induced = lymphoma in=20 allogeneic transplant recipients. Blood 1998;92(5):1549--55.=20
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Josephson A, Gombert ME. Airborne transmission of nosocomial = varicella from localized zoster. J Infect Dis = 1988;158(1):238--41.=20
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Selby PJ, Powles RL, Easton D, et al. Prophylactic role of=20 intravenous and long-term oral acyclovir after allogeneic bone = marrow=20 transplantation. Br J Cancer 1989;59(3):434--8.=20
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Redman RL, Nader S, Zerboni L, et al. Early reconstitution = of=20 immunity and decreased severity of herpes zoster in bone marrow=20 transplant recipients immunized with inactivated varicella = vaccine. J=20 Infect Dis 1997;176(3):578--85.=20
Garcia R, Raad I, Abi-Said D, et al. Nosocomial respiratory=20 syncytial virus infections: prevention and control in bone = marrow=20 transplant patients. Infect Control Hosp Epidemiol = 1997;18(6):412--6.=20
Raad I, Abbas J, Whimbey E. Infection control of nosocomial=20 respiratory viral disease in the immunocompromised host. Am J = Med=20 1997;102(3A):48--52.=20
Sable CA, Hayden FG. Orthomyxoviral and paramyxoviral = infections in=20 transplant patients [Review]. Infect Dis Clin North Am=20 1995;9(4):987--1003.=20
Whimbey E, Champlin R, Couch RB, et al. Community = respiratory virus=20 infections among hospitalized adult bone marrow transplant = recipients.=20 Clin Infect Dis 1996;22(5):778--82.=20
Whimbey E, Englund JA, Couch RB. Community respiratory virus = infections in immunocompromised patients with cancer. Am J Med=20 1997;102(3A):10--8.=20
Bowden RA. Respiratory virus infections in bone marrow = transplant:=20 the Fred Hutchinson Cancer Research Center experience. Am J Med=20 1997;102(3A):27--30.=20
Harrington RD, Hooton RD, Hackman RC, et al. Outbreak of = respiratory=20 syncytial virus in a bone marrow transplant center. J Infect Dis = 1992;165(6):987--93.=20
Whimbey E, Champlin R, Englund JA, et al. Combination = therapy with=20 aerosolized ribavirin and intravenous immunoglobulin for = respiratory=20 syncytial virus disease in adult bone marrow transplant = recipients. Bone=20 Marrow Transplant 1995;16(3):393--9.=20
Folz RJ, Elkordy MA. Coronavirus pneumonia following = autologous bone=20 marrow transplantation for breast cancer. Chest = 1999;115(3):901--5.=20
Whimbey E, Elting LS, Couch RB, et al. Influenza A virus = infection=20 among hospitalized adult bone marrow transplant recipients. Bone = Marrow=20 Transplant 1994;13(4):437--40.=20
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Engelhard D, Nagler A, Hardan I, et al. Antibody response to = a=20 two-dose regimen of influenza vaccine in allogeneic T = cell-depleted and=20 autologous BMT recipients. Bone Marrow Transplant = 1993;11(1):1--5.=20
Hayden FG. Prevention and treatment of influenza in=20 immunocompromised patients. Am J Med 1997;102(3A):55--60.=20
Monto AS, Robinson DP, Herlocher ML, Hinson JM Jr, Elliott = MJ, Crisp=20 A. Zanamivir in the prevention of influenza among healthy = adults: a=20 randomized controlled trial. JAMA 1999;282(1):31--5.=20
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Win N, Mitchell D, Pugh S, Russell NH. Successful therapy = with=20 ribavirin of late onset respiratory syncytial virus pneumonitis=20 complicating allogeneic bone transplantation. Clin Lab Haematol=20 1992;14(1):29--32.=20
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Fungal Infections

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Slavin MA, Osborne B, Adams R, et al. Efficacy and safety of = fluconazole prophylaxis for fungal infections after marrow=20 transplantation---a prospective, randomized, double-blind study. = J=20 Infect Dis 1995;171(6):1545--52.=20
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Bowden RA, Cays M, Gooley T, Mamelok RD, van Burik JA. Phase = I study=20 of amphotericin B colloidal dispersion for the treatment of = invasive=20 fungal infections after marrow transplant. J Infect Dis=20 1996;173(5):1208--15.=20
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Wade JC. Chapter 5: epidemiology of Candida = infections. In:=20 Bodey GP, ed. Candidiasis: pathogenesis, diagnosis and = treatment. New=20 York, NY: Raven Press, Ltd., 1993:85--107.=20
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Poirier JM, Berlioz F, Isnard F, Chrymol G. Marked intra- = and=20 inter-patient variability of itraconazole steady state plasma=20 concentrations. Th=E9rapie 1996;51(2):163--7.=20
Prentice AG, Warnock DW, Johnson SA, Phillips MJ, Oliver DA. = Multiple dose pharmacokinetics of an oral solution of = itraconazole in=20 autologous bone marrow transplant recipients. J Antimicrob = Chemother=20 1994;34(2):247--52.=20
Tam JY, Hamed KA, Blume K, Prober CG. Use of itraconazole in = treatment of prevention of invasive aspergillosis in bone marrow = transplant recipients [Abstract 813]. 33^rd = Interscience=20 Conference on Antimicrobial Agents and Chemotherapy (ICAAC), New = Orleans, LA, 1993;268.=20
Ortho Biotech, Inc. Itraconazole. In: Physician's desk = reference=20 (PDR), Montvale, NJ: Medical Economics Company, 2000:2131--4.=20
Denning DW. Invasive aspergillosis [Review]. Clin Infect Dis = 1998;26(4):781--803; quiz 804--5.=20
McWhinney PHM, Kibbler CC, Hamon MD, et al. Progress in the=20 diagnosis and management of aspergillosis in bone marrow=20 transplantation: 13 years' experience. Clin Infect Dis=20 1993;17(3):397--404.=20
Lupinetti FM, Behrendt DM, Giller RH, Trigg ME, de Alarcon = P.=20 Pulmonary resection for fungal infection in children undergoing = bone=20 marrow transplantation. J Thorac Cardiovasc Surg = 1992;104(3):684--7.=20
Richard C, Romon I, Baro J, et al. Invasive pulmonary = aspergillosis=20 prior to BMT in acute leukemia patients does not predict a poor = outcome.=20 Bone Marrow Transplant 1993;12(3):237--41.

Protozoal and Helminthic Infections

Brazinsky JH, Phillips JE. Pneumocystis pneumonia = transmission=20 between patients with lymphoma. JAMA 1969;209(10):1527.=20
Chave JP, David S, Wauters JP, Van Meller G, Francioli P.=20 Transmission of Pneumocystic carinii from AIDS patients = to other=20 immunosuppressed patients: a cluster of Pneumo-cystis = carinii=20 pneumonia in renal transplant patients. AIDS 1991;5(8):927--32.=20
Goesch TR, G=F6tz G, Stellbrinck KH, Albrecht H. Weh HJ, = Hossfeld DK.=20 Possible transfer of Pneumocystis carinii between = immunodeficient=20 patients [Letter]. Lancet 1990;336(8715): 627.=20
Bensousan T, Garo B, Islam S, Bourbigot B, Cledes J, Garre = M.=20 Possible transfer of Pneumocystic carinii between kidney=20 transplant recipients [Letter]. Lancet 1990;336(8722):1066--7.=20
Ruskin J, Remington JS. Compromised host and infection. I:=20 Pneumocystic carinii pneumonia. JAMA = 1967;202(12):1070--4.=20
Watanabe JM, Chinchinian H, Weitz C, McIlvanie SK. = Pneumocystis=20 carinii pneumonia in a family. JAMA 1965;193(8):685--6.=20
Tuan IZ, Dennison D, Weisdorf DJ. Pneumocystis = carinii=20 pneumonitis following bone marrow transplantation. Bone Marrow=20 Transplant 1992;10(3):267--72.=20
Maltezou HC, Petropoulos D, Choroszy M, et al. Dapsone for=20 Pneumocystic carinii prophylaxis in children undergoing = bone=20 marrow transplantation [Review]. Bone Marrow Transplant=20 1997;20(10):879--81.=20
Link H, V=F6hringer H-F, Wingen F, Bragas B, Schwardt A, = Ehninger G.=20 Pentamidine aerosol prophylaxis of Pneumocystis carinii = pneumonia=20 after BMT. Bone Marrow Transplant 1993;11(5):403--6.=20
Chan C, Montaner J, Lefebvre EA, et al. Atovaquone = suspension=20 compared with aerosolized pentamidine for prevention of = Pneumocystis=20 carinii pneumonia in human immuno-deficiency virus-infected = subjects=20 intolerant of trimethoprim or sulfonamides. J Infect Dis=20 1999;180(2):369--76.=20
Nunn PP, Allistone JC. Resistance to = trimethoprim-sulfamethoxazole=20 in the treatment of Pneumocystis carinii pneumonia: = implication=20 of folinic acid. Chest 1984;86(1):149--50.=20
Safrin S, Lee BL, Sande MA. Adjunctive folinic acid with=20 trimethoprim-sulfamethoxazole for Pneumocystic carinii = pneumonia=20 in AIDS patients is associated with an increased risk of = therapeutic=20 failure and death. J Infect Dis 1994;170(4):912--7.=20
Martino R, Mart=EDnez, Brunet S, Sureda A. Successful bone = marrow=20 transplantation in patients with recent Pneumocystis = carinii=20 pneumonia: report of two cases [Letter]. Bone Marrow Transplant=20 1995;16(3):491.=20
Castagnola E, Dini G, Lanino E, et al. Low CD4 lymphocyte = count in a=20 patient with P. carinii pneumonia after autologous bone = marrow=20 transplantation. Bone Marrow Transplant 1995;15(16):977--8.=20
Derouin F, Devergie A, Auber P, et al. Toxoplasmosis in bone = marrow=20 transplant recipients: report of seven cases and review = [Review]. Clin=20 Infect Dis 1992;15(2):267--70.=20
Koneru B, Anaissie E, Tricot G, et al. High incidence of and = mortality from Toxoplasma gondii infections in T-cell = depleted=20 allogeneic bone marrow transplant recipients [Abstract 987].=20 39^th Annual American Society of Hematology Meeting, = San=20 Diego, CA, December 5--9, 1997;224A.=20
Siegel SE, Lunde MN, Gelderman AH, et al. Transmission of=20 toxoplasmosis by leukocyte transfusion. Blood = 1971;37(4):388--94.=20
Slavin MA, Meyers JD, Remington JS, Hackman RC. = Toxoplasma=20 gondii infection in marrow transplant recipients: a 20 year=20 experience. Bone Marrow Transplant 1994;13(5): 549--57.=20
Jurges E, Young Y, Eltumi M, et al. Transmission of = toxoplasmosis by=20 bone marrow transplant associated with Campath-1G. Bone Marrow=20 Transplant 1992;9(1):65--6.=20
Chandrasekar PH, Momin F, Bone Marrow Transplant Team. = Disseminated=20 toxoplasmosis in marrow recipients: a report of three cases and = a review=20 of the literature. Bone Marrow Transplant 1997;19(7):685--9.=20
Foot ABM, Garin YJF, Ribaud P, Devergie A, Derouin F, = Gluckman E.=20 Prophylaxis of toxoplasmosis with pyrimethamine/sulfadoxine = (Fansidar)=20 in bone marrow transplant recipients. Bone Marrow Transplant=20 1994;14(2):241--5.=20
Peacock JE Jr, Greven CM, Cruz JM, Hurd DD. Fansidar: = reactivation=20 toxoplasmic retinochoroiditis in patients undergoing bone marrow = transplantation: is there a role for chemoprophylaxis [Review]? = Bone=20 Marrow Transplant 1995;15(6):983--7.=20
Liu LX, Weller PF. Strongyloidiasis and other intestinal = nematode=20 infections [Review]. Infect Dis Clin North Am 1993;7(3):655--82. =
Conway DJ, Atkins NS, Lillywhite JE, et al. Immunodiagnosis = of=20 Strongyloides stercoralis infection: a method for = increasing the=20 specificity of the indirect ELISA. Trans R Soc Trop Med Hyg=20 1993;87(2):173--6.=20
Fishman JA. Pneumocystis carinii and parasitic = infections in=20 the immunocompromised host. In: Rubin RH, Young LS, eds. = Clinical=20 approach to infection in the compromised host 3^rd = edition.=20 New York, NY: Plenum Medical Book Company, 1994;275--334.=20
Fishman JA. Pneumocystis carinii and parasitic = infections in=20 transplantation. Infect Dis Clin North Am 1995;9(4):1005--44.=20
Leiby DA, Fucci MH, Stumpf RJ. Trypanosoma cruzi in a = low- to=20 moderate-risk blood donor population: seroprevalence and = possible=20 congenital transmission. Transfusion 1999;39(3):310--5.=20
Dictar M, Sinagra A, Ver=F3n MT, et al. Recipients and = donors of bone=20 marrow transplants suffering from Chagas' disease: management = and=20 preemptive therapy of parasitemia. Bone Marrow Transplant=20 1998;21(4):391--3.=20
Moraes-Souza H, Bordin JO. Strategies for prevention of=20 transfusion-associated Chagas' disease. Transfus Med Rev=20 1996;10(3):161--70.=20
Altclas J, Sinagra A, Jaimovich G, et al. Reactivation of = chronic=20 Chagas' disease following allogeneic bone marrow transplantation = and=20 successful pre-emptive therapy with benznidazole. Transplant = Infectious=20 Disease 1999;1:135--7.=20
Altclas J, Jaimovich G, Milovic V, Klein F, Feldman L. = Chagas'=20 disease after bone marrow transplantation. Bone Marrow = Transplant=20 1996;18(2):447--8.

Hospital Infection Control

Streifel AJ. Chapter 80: design and maintenance of hospital=20 ventilation systems and the prevention of airborne nosocomial=20 infections. In: Mayhall CG, ed. Hospital epidemiology and = infection=20 control. 2^nd ed. Philadelphia, PA: Lippincott = Williams &=20 Wilkins 1999; 1211--21.=20
Streifel AJ, Marshall JW. Parameters for ventilation = controlled=20 environments in hospitals. In: Moschandreas DJ, ed. Design,=20 construction, and operation of healthy buildings; solutions to = global=20 and regional concerns. Atlanta, GA: American Society of Heating, = Refrigerating and Air-Conditioning Engineers Press, 1998;305--9. =
Barnes RA, Rogers TR. Control of an outbreak of nosocomial=20 aspergillosis by laminar airflow isolation. J Hosp Infect=20 1989;14(2):89--94.=20
Sheretz FJ, Belani A, Kramer BS, et al. Impact of air = filtration on=20 nosocomial Aspergillus infections: unique risk to bone = marrow=20 transplant recipients. Am J Med 1987;83(4):709--18.=20
Walter EA, Bowden RA. Infection in the bone marrow = transplant=20 recipient [Review]. Infect Dis Clin North Am 1995;9(4):823--47.=20
Storb R, Prentice RL, Buckner CD, et al. Graft-versus-host = disease=20 and survival in patients with aplastic anemia treated by marrow = grafts=20 from HLA-identical siblings. N Engl J Med 1983;308(6):302--7.=20
Streifel AJ. Maintenance and engineering; biomedical = engineering;=20 support services and facilities management. In: Association for=20 Professionals in Infection Control and Epidemiology, Inc. = Principles and=20 practice. 2^nd ed. St. Louis, MO: Mosby, 2000 (in = press).=20
Vesley D, Streifel AJ. Chapter 69: environmental services. = In:=20 Mayhall CG, ed. Hospital epidemiology and infection control.=20 2^nd ed. Philadelphia, PA: Lippincott Williams & = Wilkins,=20 1999;1047--53.=20
Carter CD, Barr BA. Infection control issues in construction = and=20 renovation. Infect Control Hosp Epidemiol 1997;18(8):587--96.=20
Loo VG, Bertrand C, Dixon C, et al. Control of=20 construction-associated nosocomial aspergillosis in an = antiquated=20 hematology unit. Infect Control Hospital Epidemiol = 1996;17(6):360--4.=20
Rask DR, Dziekan B, Swincicki WC, et al. Air quality control = during=20 renovation in health care facilities. In: Moschandreas DJ, ed. = Design,=20 construction, and operation of healthy buildings; solutions to = global=20 and regional concerns. Atlanta, GA: American Society of Heating, = Refrigerating, and Air-Conditioning Engineers Press, = 1998:291--304.=20
CDC. Laboratory performance evaluation of N95 filtering = facepiece=20 respirators, 1996. MMWR 1998;47(48):1045--9.=20
CDC. Guidelines for preventing the transmission = Mycobacterium=20 tuberculosis in health- care facilities, 1994. MMWR = 1994;43(No.=20 RR-13):1--132.=20
CDC/National Institute of Occupational Safety and Health. = Protect=20 yourself against tuberculosis---a respiratory protection guide = for=20 health care workers. Cincinnati, OH: US Department of Health and = Human=20 Services, US Public Health Service, CDC, National Institute for=20 Occupational Health and Safety, 1995; DHHS publication no. = (NIOSH)=20 96-102:1--132. Available at <http://www.cdc.gov/niosh>.=20 Accessed May 15, 2000.=20
Rutala WA. APIC guideline for selection and use of = disinfectants. Am=20 J Infect Control 1996;24(4):313--42.=20
National Antimicrobial Information Network. List of EPA = registered=20 products. Available at <http://ace.orst.edu/info= /nain/lists.htm>.=20 Accessed May 15, 2000.=20
Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR, = Hospital=20 Infection Control Practices Advisory Committee. Guideline for = prevention=20 of surgical site infection, 1999. Infect Control Hosp Epidemiol=20 1999;20(4):247--80 or Am J Infect Control 1999;27(2): 97--134.=20
Garner JS, Favero MS. Guideline for handwashing and hospital = environmental control, 1985; supersedes guideline for hospital=20 environmental control published in 1981. Available at <http://www.cdc.= gov/ncidod/hip/Guide/handwash.htm>.=20 Accessed May 15, 2000.=20
Rotter ML. Chapter 87: hand washing and hand disinfection. = In:=20 Mayhall CG, ed. Hospital epidemiology and infection control.=20 2^nd ed. Baltimore, MD: Lippincott Williams and = Wilkins,=20 1999:1339--55.=20
Larson EL. APIC guideline for handwashing and hand = antisepsis in=20 health care settings. Am J Infect Control 1995;23(4):251--69.=20
McNeil SA, Foster CL, Kauffman CA. Effect of hand cleansing = with=20 antimicrobial soap gel on microbial colonization of artificial = nails=20 (AN) [Abstract 1696]. 39^th Interscience Conference on = Antimicrobial Agents and Chemotherapy Abstracts, San Francisco, = CA,=20 1999;635.=20
CDC/National Center for Infectious Diseases/Hospital = Infections=20 Program. Sterilization or disinfection of medical devices: = general=20 principles. Atlanta, GA: US Department of Health and Human = Services,=20 CDC, 2000. Available at <http://www.cd= c.gov/ncidod/hip/sterile/sterilgp.htm>.=20 Accessed May 15, 2000.=20
Favero MS, Bond WW. Chapter 24: sterilization, disinfection, = and=20 antisepsis in the hospital. In: Hauser WJ Jr, Herrmann KL, = Isenberg HD,=20 Shadomy HJ, eds. Manual of clinical microbiology. Washington DC: = American Society for Microbiology, 1991:183--200.=20
Johnson S, Gerding DN. Chapter 29: Clostridium = difficile. In:=20 Mayhall CG, ed. Hospital epidemiology and infection control.=20 2^nd ed., Philadelphia, PA: Lippincott Williams & = Wilkins,=20 1999:467--76.=20
Rutala WA, Weber DJ. Disinfection of endoscopes: review of = new=20 chemical sterilants used for high-level disinfection. Infect = Control and=20 Hospital Epidemiol 1999;20(1):69--75; published erratum, Infect = Control=20 Hosp Epidemiol 1999;20(5):302.=20
CDC. Nosocomial outbreak of Rhizopus infections = associated=20 with Elastoplast^=AE wound dressings---Minnesota. MMWR = 1978;27(5):33--4.=20
CDC. Follow-up on Rhizopus infections associated with = Elastoplast^=AE bandages---United States. MMWR=20 1978;27(28):243--4.=20
Bryce EA, Walker M, Scharf S, et al. Outbreak of cutaneous=20 aspergillosis in a tertiary-care hospital. Infect Control Hosp = Epidemiol=20 1996;17(3):170--2.=20
McCarty JM, Flam MS, Pullen G, Jones R, Kassel SH. Outbreak = of=20 primary cutaneous aspergillosis related to intravenous arm = boards. J=20 Pediatr 1986;108(5 Pt 1):721--4.=20
Mitchell SJ, Gray J, Morgan MEI, Hocking MC, Durbin GM. = Nosocomial=20 infection with Rhizopus microsporus in preterm infants:=20 association with wooden tongue depressors. Lancet = 1996;348(9025):441--3.=20
Gerson SL, Parker P, Jacobs MR, Creger R, Lazarus HM. = Aspergillosis=20 due to carpet contamination [Letter]. Infect Control Hosp = Epidemiol=20 1994;15(4 Pt 1):221--3.=20
Richet H, McNeil M, Pewters W, et al. Aspergillus = flavus in a=20 bone marrow transplant unit (BMTU): pseudofungemia traced to = hallway=20 carpeting [Abstract F-23]. 89^th Annual Meeting of the = American Society for Microbiology, New Orleans, Louisiana, May = 14--18,=20 1989:462.=20
Staib F. Ecological and epidemiological aspects of = Aspergilli=20 pathogenic for man and animal in Berlin (West). Zentrablatt fur=20 Bakteriologie, Mikrobiologie, und Hygiene---Series A = 1984;257(2):240--5.=20
CDC. ABCs of safe and healthy child care: an on-line = handbook for=20 child care providers. Atlanta, GA: US Department of Health and = Human=20 Services, CDC, 2000. Available at <http://www.cdc.gov/nci= dod/hip/ABC/abc.htm>.=20 Accessed May 15, 2000.=20
Buttery JP, Alabaster SJ, Heine RG, et al. Multiresistant=20 Pseudomonas aeruginosa outbreak in a pediatric oncology = ward=20 related to bath toys. Pediatr Infect Dis J 1998;17(6):509--13.=20
CDC. Immunization of health care workers: recommendations of = the=20 Advisory Committee on Immunization Practices (ACIP) and the = Hospital=20 Infection Control Practices Advisory Committee. MMWR 1997;46(No. = RR-18):1--42.=20
Bolyard EA, Tablan OC, Williams WW, et al. Guideline for = infection=20 control in health care personnel. Infect Control Hospital = Epidemiol=20 1998;19(6):407--63.=20
Stover BH, Bratcher DF. Varicella-zoster virus: infection, = control,=20 and prevention [Review]. Am J Infect Control 1998;26(3):369--83; = quiz=20 382--4.=20
Schubert MM, Peterson DE, Lloid ME. Oral complications. In: = Thomas=20 ED, Blume KG, Forman SJ, eds. Hematopoietic cell = transplantation.=20 2^nd ed. Oxford, England: Blackwell Science, Inc.,=20 1999;751--63.=20
Wilkes JD. Prevention and treatment of oral mucositis = following=20 cancer chemotherapy [Review]. Semin Oncol 1998;25(5):538--51.=20
Toscano CM, Bell M, Zukerman C, et al. Bloodstream = infections (BSI)=20 associated with needleless device use, bathing practices and = home=20 infusion [Poster abstract P3]. 48^th Annual Epidemic=20 Intelligence Service Conference, April 19--23, 1999, Atlanta, = GA;47.=20
Do AN, Ray BJ, Banerjee SN, et al. Bloodstream infection = associated=20 with needleless device use and the importance of = infection-control=20 practices in the home health care setting. J Infect Dis=20 1999;179(2):442--8.=20
Kool JL, Fiore AE, Kioski CM, et al. More than 10 years of=20 unrecognized nosocomial transmission of Legionnaires' disease = among=20 transplant patients. Infect Control Hosp Epidemiol = 1998;19(12):898--904.=20
CDC. Sustained transmission of nosocomial Legionnaires'=20 disease---Arizona and Ohio. MMWR 1997;46(19):416--21.=20
Lepine LA, Jernigan DB, Butler JC, et al. Recurrent outbreak = of=20 nosocomial Legionnaires' disease detected by urinary antigen = testing:=20 evidence for long-term colonization of a hospital plumbing = system.=20 Infect Control Hosp Epidemiol 1998;19(12):905--10.=20
Muraca PW, Yu VL, Goetz A. Disinfection of water = distribution=20 systems for Legionella: a review of application = procedures and=20 methodologies [Review]. Infect Control Hosp Epidemiol = 1990;11(2):79--88.=20
Harbarth S, Dharan S, Liassine N, Herrault P, Auckenthaler = R, Pittet=20 D. Randomized, placebo-controlled, double-blind trial to = evaluate the=20 efficacy of mupirocin for eradicating carriage of = methicillin-resistant=20 Staphylococcus aureus. Antimicrob Agents Chemother=20 1999;43(6):1412--6.=20
Leski TA, Gniadkowski M, Skoczynska A, Stefaniuk E, = Trzcinski K,=20 Hryniewicz W. Outbreak of mupirocin-resistant = Staphylococci in a=20 hospital in Warsaw, Poland, due to plasmid transmission and = clonal=20 spread of several strains. J Clin Microbiol 1999;37(9):2781--8.=20
Schmitz FJ, Lindenlauf E, Hofmann B, et al. Prevalence of = low- and=20 high-level mupirocin resistance in Staphylococci from 19 = European=20 hospitals. J Antimicrob Chemother 1998;42(4):489--95.=20
Irish D, Eltringham I, Teall A, et al. Control of an = outbreak of an=20 epidemic methicillin-resistant Staphylococcus aureus also = resistant to mupirocin. J Hosp Infect 1998;39(1): 19--26.=20
Udo EE, Farook VS, Mokadas EM, Jacob LE, Sanyal SC. = Molecular=20 fingerprinting of mupirocin-resistant methicillin-resistant=20 Staphylococcus aureus from a burn unit. Int J Infect Dis=20 1998--99;3(2):82--7.=20
Bastos MC, Mondino PJ, Azevedo ML, Santos KR, = Giambiagi-deMarval M.=20 Molecular characterization and transfer among = Staphylococcus=20 strains of a plasmid conferring high-level resistance to = mupirocin. Eur=20 J Clin Microbiol Infect Dis 1999;18(6):393--8.=20
CDC. Recommendations for preventing the spread of vancomycin = resistance: recommendations of the Hospital Infection Control = Practices=20 Advisory Committee (HICPAC). MMWR 1995;44(No. RR-12):1--13.=20
CDC. Update: Staphylococcus aureus with reduced=20 susceptibility to vancomycin---United States, 1997. MMWR=20 1997;46(35):813--5.=20
Smith TL, Pearson ML, Wilcox KR, et al. Emergence of = vancomycin=20 resistance in Staphylococcus aureus. N Engl J Med=20 1999;340(7):493--501.=20
CDC. Interim guidelines for prevention and control of = staphylococcal=20 infection associated with reduced susceptibility to vancomycin. = MMWR=20 1997;46(27):626--35.=20
CDC. Reduced susceptibility of Staphylococcus aureus = to=20 vancomycin---Japan, 1996. MMWR 1997;46(27):624--35.=20
Waldvogel FA. New resistance in Staphylococcus = aureus. N Engl=20 J Med 1999;340(7): 556--7.=20
Montecalvo MA, Shay DK, Patel P, et al. Bloodstream = infections with=20 vancomycin-resistant Enterococci. Arch Intern Med=20 1996;156:1458--62.=20
Hospital Infection Control Practices Advisory Committee = (HICPAC).=20 Recommendations for preventing the spread of vancomycin = resistance.=20 Infect Control Hosp Epidemiol 1995;16:105--13.=20
Kirkpatrick BD, Harrington SM, Smith D, et al. Outbreak of=20 vancomycin-dependent Enterococcus faecium in a bone = marrow=20 transplant unit. Clin Infect Dis 1999;29(5):1268--73.=20
Byers KE, Durbin LJ, Simonton BM, Anglim AM, Adel KA, Farr = BM.=20 Disinfection of hospital rooms contaminated with = vancomycin-resistant=20 Enterococcus faecium. Infect Control Hosp Epidemiol=20 1998;19(4):261--4.=20
Trick WE, Kuehnert MJ, Quirk SB, et al. Regional = dissemination of=20 vancomycin-resistant Enterococci resulting from = interfacility=20 transfer of colonized patients. J Infect Dis 1999;180(2):391--6. =
Gerding DN, Johnson S, Peterson LR, Mulligan ME, Silva J Jr. = Clostridium difficile-associated diarrhea and colitis = [Review].=20 Infect Control Hosp Epidemiol 1995;16(8): 459--77.=20
Johnson S, Gerding DN. Clostridium = difficile-associated=20 diarrhea. Clin Infect Dis 1998;26:1027--36; quiz 1035--6.=20
McFarland LV, Mulligan M, Kwok RY, Stamm WE. Nosocomial = acquisition=20 of Clostridium difficile infection. N Engl J Med=20 1989;321(3):204--10.=20
Johnson S, Gerding DN, Olson MM, et al. Prospective, = controlled=20 study of vinyl glove use to interrupt Clostridium = difficile=20 nosocomial transmission. Am J Med 1990;88(2): 137--40.=20
Pear SM, Williamson T, Bettin K, Gerding DN, Galgiami JN. = Decrease=20 in nosocomial Clostridium difficile-associated diarrhea = by=20 restricting clindamycin use. Ann Intern Med 1994;120(4):272--7.=20
Kaatz GW, Gitlin SD, Schaberg DR et al. Acquisition of=20 Clostridium difficile from the hospital environment. Am J = Epidemiol 1988;127(6):1289--94.=20
Delmee M, Vandercam B, Avesani V, Michaux JL. Epidemiology = and=20 prevention of Clostridium difficile infections in a = leukemia=20 unit. Eur J Clin Microbiol 1987;6(6):623--7.=20
Johnson S, Homann SR, Bettin KM, et al. Treatment of = asymptomatic=20 Clostridium difficile carriers (fecal excretors) with = vancomycin=20 or metronidazole. Ann Intern Med 1992;117(4):297--302.=20
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Strategies for Safe Living After HSCT -- Prevention of = Exposure and=20 Disease

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American Academy of Pediatrics. Cryptosporidiosis. In: = Pickering LK,=20 ed. 2000 red book: report of the Committee on Infectious = Diseases.=20 25^th ed. Elk Grove Village, IL: American Academy of=20 Pediatrics 2000:223--4.=20
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Dalton C, Hoffman R, Pape J. Iguana-associated salmonellosis = in=20 children. Pediatr Infect Dis J 1995;14(4):319--20.=20
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CDC. Errata: Reptile-associated salmonellosis---selected = states,=20 1996--1998. MMWR 1999;48(45):1051.=20
Mermin J, Hoar B, Angulo FJ. Iguanas and Salmonella = marina=20 infection in children: a reflection of the increasing incidence = of=20 reptile-associated salmonellosis in the United States. Pediatr=20 1997;99(3):399--402.=20
CDC. Salmonellosis associated with chicks and = ducklings---Michigan=20 and Missouri, Spring 1999. MMWR 2000;49(14):297--9.=20
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CDC. Outbreak of cryptosporidiosis associated with a water = sprinkler=20 foundation---Minnesota, 1997. MMWR 1998;47(40):856--60.=20
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Keene WE, Hedberg K, Herriott DE, et al. Prolonged outbreak = of=20 Escherichia coli O157:H7 infections caused by = commercially=20 distributed raw milk. J Infect Dis 1997;176(3):815--8.=20
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CDC. Outbreaks of Escherichia coli O157:H7 infection = and=20 cryptosporidiosis associated with drinking unpasteurized apple=20 cider---Connecticut and New York, October 1996. MMWR = 1997;46(1):4--8.=20
CDC. Outbreak of Salmonella serotype Muenchen = infections=20 associated with unpasteurized orange juice---United States and = Canada,=20 June 1999. MMWR 1999;48(27): 582--5.=20
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CDC. Foodborne outbreak of cryptosporidiosis---Spokane, = Washington,=20 1997. MMWR 1998;47(27):565--7.=20
US Department of Agriculture/Food Safety and Inspection = Service. Big=20 thaw---safe defrosting methods. Washington, DC: US Department of = Agriculture, Food Safety and Inspection Service, Consumer = Education and=20 Information, 1996;1--2. Available at <http://www.fsis.usd= a.gov/OA/news/bigthaw.htm>.=20 Accessed May 15, 2000.=20
US Department of Agriculture/Food Safety and Inspection = Service.=20 Kitchen thermometers. Washington, DC: US Department of = Agriculture=20 Consumer, Food Safety and Inspection Service, Education and = Information,=20 2000 (in press).=20
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Aker SN, Lenssen P. Chapter 80: nutritional support of = patients with=20 hematologic malignancies. In: Benz EJ Jr, Cohen HJ, Burie B, et = al.,=20 eds. Hematology: basic principles and practice, 3^rd = ed. New=20 York, NY: Churchill Livingstone, 2000:1501--14.=20
Hilton E, Isenberg HD, Alperstein P, France K, Borenstein = MT.=20 Ingestion of yogurt containing Lactobacillus acidophilus = as=20 prophylaxis for candidal vaginitis. Ann Intern Med = 1992;116(5):353--7.=20
CDC. Vibrio vulnificus infections associated with = eating raw=20 oysters---Los Angeles, 1996. MMWR 1996;45(29):621--4.=20
CDC. Outbreak of Vibrio parahaemolyticus infection = associated=20 with eating raw oysters and clams harvested from Long Island=20 Sound---Connecticut, New Jersey, and New York, 1998. MMWR=20 1999;48(03):48--51.=20
CDC. Viral gastroenteritis associated with eating=20 oysters---Louisiana, December 1996--January 1997. MMWR=20 1997;46(47):1109--12.=20
Fayer R, Lewis EJ, Trout JM, et al. Cryptosporidium = parvum in=20 oysters from commercial harvesting sites in Chesapeake Bay. = Emerg Infect=20 Dis 1999;5(5):706--10.=20
Oliver MR, van Voorhis WC, Boeckh M, Mattson D, Bowden RA. = Hepatic=20 mucormycosis in a bone marrow transplant recipient who ingested=20 naturopathic medicine. Clin Infect Dis 1996;22:521--4.=20
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CDC/National Center for Infectious Diseases. Food and water=20 precautions and traveler's diarrhea prevention. Atlanta, GA: US=20 Department of Health and Human Services, CDC, 2000;1--2. = Available at=20 <http://www.cdc.gov/travel= /foodwatr.htm>.=20 Accessed May 15, 2000.=20
Belay E, Bresee JS, Holman RC, Khan AS, Shahriari A, = Schonberger LB.=20 Reye's syndrome in the United States from 1981 through 1997. New = Engl J=20 Med 1999;340(18):1377--82.

HSCT Recipient Vaccinations

Pauksen K, Hammarstr=F6m V, Ljungman P, et al. Immunity to = poliovirus=20 and immunization with inactivated poliovirus vaccine after = autologous=20 bone marrow transplantation. Clin Infect Dis 1994;18(4):547--52. =
Pauksen K, Duraj V, Ljungman P, et al. Immunity to and = immunization=20 against measles, rubella and mumps in patients after autologous = bone=20 marrow transplantation. Bone Marrow Transplant = 1992;9(6):427--32.=20
Ljungman P, Wiklund-Hammarsten M, Duraj V, et al. Responses = to=20 tetanus toxoid immunization after allogeneic bone marrow=20 transplantation. J Infect Dis 1990;162(2): 496--500.=20
Ljungman P, Fridell E, Lonnqvist B, et al. Efficacy and = safety of=20 vaccination of marrow transplant recipients with a live = attenuated=20 measles, mumps, and rubella vaccine. J Infect Dis = 1989;159(4):610--5.=20
Henning KJ, White MH, Sepkowitz KA, Armstrong D. National = survey of=20 immunization practices following allogeneic bone marrow = transplantation.=20 JAMA 1997;277(14): 1148--51.

Hematopoietic Stem Cell Safety

Padley D, Koontz F, Trigg ME, Gingrich R, Strauss RG. = Bacterial=20 contamination rates following processing of bone marrow and = peripheral=20 blood progenitor cell preparations. Transfusion = 1996;36(1):53--6.=20
National Marrow Donor Program.^=AE Standards: = effective=20 September 1, 1999. 17^th ed. Minneapolis, MN: National = Marrow=20 Donor Program, 1999:1--35.=20
Progenitor Cell Standards Task Force. Standards for = hematopoietic=20 progenitor cells. Bethesda, MD: American Association of Blood = Banks,=20 1996:1--36.=20
Foundation for the Accreditation of Hematopoietic Cell = Therapy.=20 Standards for hematopoietic progenitor cell collection, = processing and=20 transplantation. 1^st ed.-North America. Omaha, NE: = FAHCT=20 Accreditation Office, 1996:1--58.=20
Food and Drug Administration. Memorandum, June 8, 1995:=20 recommendations for the deferral of current and recent inmates = of=20 correctional institutions as donors of whole blood, blood = components,=20 source leukocytes, and source plasma. Rockville, MD: US = Department of=20 Health and Human Services, Food and Drug Administration, 1995. = Available=20 at <http://www.fda.gov/cbe= r/bldmem/6_8_95.txt>.=20 Accessed May 16, 2000.=20
American Association of Blood Banks. New uniform donor = history=20 questionnaire issued [Association bulletin 99-10]. American = Association=20 of Blood Banks News 1999;(Nov/Dec):13--21.=20
CDC. Guidelines for preventing transmission of human=20 immunodeficiency virus through transplantation of human tissue = and=20 organs. MMWR 1994;43(No. RR-8):1--17.=20
CDC. Public health service inter-agency guidelines for = screening=20 donors of blood, plasma, organs, tissues, and semen for evidence = of=20 hepatitis B and hepatitis C. MMWR 1991;40(No. RR-4):1--17.=20
Food and Drug Administration. Suitability determination for = donors=20 of human cellular and tissue-based products [Proposed rule]. = Federal=20 Register 1999;64:52696--723. Available at <http://www.fda.gov/c= ber/rules/suitdonor.pdf>.=20 Accessed May 16, 2000.=20
Wells GM, Woodward TE, Fiset P, Hornick RB. Rocky Mountain = spotted=20 fever caused by blood transfusion. JAMA 1978;239(26):2763--65.=20
Herwaldt BL, Kjemtrup AM, Conrad PA, et al. = Transfusion-transmitted=20 babesiosis in Washington State: first reported case caused by a = WA1-type=20 parasite. J Infect Dis 1997;175(5):1259--62.=20
Dobroszycki J, Herwaldt BL, Boctor F, et al. Cluster of=20 transfusion-associated babesiosis cases traced to a single = asymptomatic=20 donor. JAMA 1999;281(10):927--30.=20
CDC. Q fever---California. MMWR 1977;26(10):86, 91.=20
CDC. Transmission of Colorado tick fever virus by blood=20 transfusion---Montana. MMWR 1975;24:422--7.=20
American Association of Blood Banks. Standards for blood = banks and=20 transfusion services. 19^th ed. Bethesda, MD: American = Association of Blood Banks, 1999:1--98.=20
Klein MB, Miller JS, Nelson CM, Goodman JL. Primary bone = marrow=20 progenitors of both granulocytic and monocytic lineages are = susceptible=20 to infection with the agent of human granulocytic ehrlichiosis. = J Infect=20 Dis 1997;176(5):1405--9.=20
Dharmasena F, Gordon-Smith EC. Transmission of malaria by = bone=20 marrow transplantation [Letter]. Transplant 1986;42(2):228.=20
Villeneuve L, Cassaing S, Magnaval JF, et al. Plasmodium=20 falciparum infection following allogeneic bone-marrow=20 transplantation. Ann Trop Med Parasitol 1999;93(5):533--5.=20
Leiby DA, Lenes BA, Tibbals MA, Tames-Olmedo MT. Prospective = evaluation of a patient with Trypanosoma cruzi infection=20 transmitted by transfusion. New Engl J Med 1999; = 341(16):1237--9.=20
Leiby DA, Read EJ, Lenes BA, et al. Seroepidemiology of=20 Trypanosoma cruzi, etiologic agent of Chagas' disease, in = US=20 blood donors. J Infect Dis 1997;176:1047--52.=20
Dodd RY. Transmission of parasites by blood transfusion = [Review].=20 Vox Sang 1998;74(suppl 2):161--3.=20
Food and Drug Administration. Guidance for industry: = precautionary=20 measures to reduce the possible risk of transmission of zoonoses = by=20 blood and blood products from xenotransplantation products = recipients=20 and their contacts---12/23/99 [Draft guidance]. Rockville, MD: = US=20 Department of Health and Human Services, Food and Drug = Administration,=20 1999;1--11. Available at <http://www.fda.gov/cber/g= uidelines.htm>.=20 Accessed May 16, 2000.=20
CDC. Creutzfeldt-Jakob disease associated with cadaveric = dura mater=20 grafts---Japan, January 1979--May 1996. MMWR = 1997;46(45):1066--9.=20
Food and Drug Administration. Guidance for industry: revised = precautionary measures to reduce the possible risk of = transmission of=20 Creutzfeldt-Jakob Disease (CJD) and new variant = Creutzfeldt-Jakob=20 disease (nvCJD) by blood and blood products---11/23/99. = Rockville, MD:=20 US Department of Health and Human Services, Food and Drug=20 Administration, 1999;1--16. Available at <http://www.fda.gov/cber/g= uidelines.htm>.=20 Accessed May 16, 2000.=20
Will RG, Alpers MP, Dormont D, Schonberger LB, Tateishi J.=20 Infectious and sporadic prion diseases. In: Prusiner SB, ed. = Prion=20 biology and diseases. Cold Spring Harbor, NY: Cold Spring Harbor = Laboratory Press, 1999:465--507.=20
Food and Drug Administration. Memorandum, April 23, 1992: = revised=20 recommendations for the prevention of Human Immunodeficiency = Virus (HIV)=20 transmission by blood and blood products. Rockville, MD: US = Department=20 of Health and Human Services, Food and Drug Administration, = 1992:1--24.=20 Available at <http://www.fda.gov/cber/memo.ht= m>.=20 Accessed May 16, 2000.=20
Pugatch D, Mileno M, Rich JD. Possible transmission of human = immunodeficiency virus type 1 from body piercing. Clin Infect = Dis=20 1998;26(3):767--8.=20
CDC. 1995 revised guidelines for prophylaxis against = Pneumocystic=20 carinii pneumonia for children infected with or perinatally = exposed=20 to human immunodeficiency virus. MMWR 1995;44(No. RR-4):1--11.=20
Attarian H, Bensinger WI, Buckner CD, McDonald DL, Rowley = SD.=20 Microbial contamination of peripheral blood stem cell = collections. Bone=20 Marrow Transplant 1996;17(5):699--702.=20
Rowley SD, Davis J, Dick J, et al. Bacterial contamination = of bone=20 marrow grafts intended for autologous and allogeneic bone marrow = transplantation: incidence and clinical significance. = Transfusion=20 1988;28(2):109--12.=20
Webb IJ, Coral FS, Andersen JW, et al. Sources and sequelae = of=20 bacterial contamination of hematopoietic cell components: = implications=20 for the safety of hematotherapy and graft engineering. = Transfusion=20 1996;36(9):782--8.=20
Meyers JD, Huff JC, Holmes KK, Thomas ED, Bryan JA. = Parenterally=20 transmitted hepatitis A associated with platelet transfusions:=20 epidemiologic study of an outbreak in a marrow transplantation = center.=20 Ann Intern Med 1974;81(2):145--51.=20
Fountain D, Ralston M, Higgins N, et al. Liquid nitrogen = freezers: a=20 potential source of microbial contamination of hematopoietic = stem cell=20 components. Transfusion 1997;37(6):585--91.=20
Nasser RM, Hajjar I, Sandhaus LM, et al. Routine cultures of = bone=20 marrow and peripheral stem cell harvests: clinical impact, cost=20 analysis, and review. Clin Infect Dis 1998;27(4): 886--8.=20
Flake AW, Roncarolo MG, Puck JM, et al. Treatment of = x-linked severe=20 combined immunodeficiency by in utero transplantation of = paternal bone=20 marrow. N Engl J Med 1996;335(24):1806--10.=20
Flake AW, Zanjani ED. In utero hematopoietic stem cell=20 transplantation: a status report. JAMA 1997;278(11):932--7.=20

* For this report, HSCT is defined as any transplantation of = blood- or=20 marrow-derived hematopoietic stem cells, regardless of transplant = type=20 (e.g., allogeneic or autologous) or cell source (e.g., bone = marrow,=20 peripheral blood, or placental/umbilical cord blood). In addition, = HSCT=20 recipients are presumed immunocompetent at >24 months = after HSCT=20 if they are not on immunosuppressive therapy and do not have=20 graft-versus-host disease (GVHD), a condition that occurs when the = transplanted cells recognize that the recipient's cells are not = the same=20 cells and attack them.

** Presently, no updated data have been published.

*** Since November 1997, the United States has had a shortage = of=20 intravenous immunoglobulin (IVIG) (Source: CDC. = Availability of=20 immune globulin intravenous for treatment of immune deficient=20 patients---United States, 1997--1998. MMWR 1999:48[8];159--162).=20 Physicians who have difficulty obtaining IVIG should contact the = following=20 sources:=20

American Red Cross Customer Service Center, (800) 261-5772;=20
Alpha Therapeutic Corporation, (800) 421-0008;=20
Baxter Healthcare Corporation, (847) 940-5955;=20
Bayer Pharmaceutical Division, (800) 288-8370;=20
Aventis Behring Customer Support, (800) 683-1288;=20
Novartis Pharmaceuticals Corporation, (973) 781-8300, or the = IVIG=20 Emergency Hotline, (888) 234-2520; or=20
Immune Deficiency Foundation, (800) 296-4433.

Physicians who are unable to obtain IVIG for a licensed = indication from=20 one of these sources should contact the Product Shortage Officer = at the=20 Food and Drug Administration's Center for Biologics Evaluation and = Research, Office of Compliance, (301) 827-6220, for assistance. =

**** VZIG is distributed by FFF Enterprises, Inc., under = contract with=20 the American Red Cross, except in Massachusetts where it is = distributed by=20 the Massachusetts Public Health Biologic Laboratories (now a unit = of the=20 University of Massachusetts) (19) . FFF Enterprises, Inc., = can be=20 contacted at

FFF Enterprises, Inc.
41093 County Center = Drive
Temecula, CA=20 92591
Phone: (800) 522-4448

***** For additional information regarding the epidemiology of = Chagas'=20 disease, contact CDC/National Center for Infectious = Diseases/Division of=20 Parasitic Diseases, (770) 488-7760.

****** Broviac dolls are used to demonstrate medical procedures = (e.g.,=20 insertion of catheters) to children to lessen their fears.

******* For a list of filters certified under NSF Standard 053 = for cyst=20 (i.e., Cryptosporidium removal, contact the NSF = International=20 consumer line at (800) 673-8010 or <http://www.nsf.org/notice/= crypto.html>.=20

******** The International Bottled Water Association can be = contacted=20 at (703) 683-5213 from 9 a.m. to 5 p.m. EST or anytime at their = Internet=20 site (<http://www.bottledwater.org/>= ;)=20 to obtain contact information regarding water bottlers.

********* The U.S. Public Health Service is reexamining the = current=20 donor deferral recommendations regarding risk behaviors for donors = of=20 organs, cells, tissues, xenotransplantation, and reproductive = cells and=20 tissue, including semen, and revisions to these guidelines could = become=20 necessary as the research evolves.

********** Guidelines for screening UCB donors and their = mothers are=20 evolving and will not be addressed in this document. =

Table 1

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Figure

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Table 2

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Table 3

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Table 4

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Table 5

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Table 6

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Table 7

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Table 8

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Appendix=20
Appendix

Dosing Charts for Preventing Opportunistic Infections Among=20 Hematopoietic Stem Cell Transplant Recipients

Disclaimer=20 All MMWR HTML versions of articles are = electronic=20 conversions from ASCII text into HTML. This conversion may have = resulted=20 in character translation or format errors in the HTML version. = Users=20 should not rely on this HTML document, but are referred to the = electronic=20 PDF version and/or the original MMWR paper copy for the = official=20 text, figures, and tables. An original paper copy of this issue = can be=20 obtained from the Superintendent of Documents, U.S. Government = Printing=20 Office (GPO), Washington, DC 20402-9371; telephone: (202) = 512-1800.=20 Contact GPO for current prices.
**Questions or messages = regarding errors in formatting should be addressed to mmwrq@cdc.gov.=20

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r=3Dtfs.document.referrer,s=3D'',c=3D'',v=3D'',p=3D'',bw=3D'',bh=3D'',j=3D= '1.0',g=3D s_wd.location,k=3Ds_c_w('s_cc','true',0)?'Y':'N',hp=3D'',ct=3D'',iepl=3Ds= _gg( 'iePlugins'),pn=3D0,ps;if(s_apv>=3D4)s=3Dscreen.width+'x'+screen.height;i= f( s_isns||s_isopera){if(s_apv>=3D3){j=3D'1.1';v=3Ds_n.javaEnabled()?'Y':'N'= if(s_apv>=3D4){j=3D'1.2';c=3Dscreen.pixelDepth;bw=3Ds_wd.innerWidth;bh=3D= s_wd.innerHeight;if(s_apv>=3D4.06)j=3D'1.3'}}s_pl=3Ds_n.plugins}else if( s_isie){if(s_apv>=3D4){v=3Ds_n.javaEnabled()?'Y':'N';j=3D'1.2';c=3D screen.colorDepth;if(s_apv>=3D5){bw=3Ds_d.documentElement.offsetWidth;bh=3D= s_d.documentElement.offsetHeight;j=3D'1.3';if(!s_ismac&&s_d.body){ s_d.body.addBehavior("#default#homePage");hp=3Ds_d.body.isHomePage(tl)? 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Guidelines for Preventing Opportunistic Infections Among = Hematopoietic=20 Stem Cell Transplant Recipients

Recommendations of CDC, the Infectious Disease Society of = America, and=20 the American Society of Blood and Marrow Transplantation

Abbreviations Used in This Publication

The following CDC staff members prepared this report: =

in collaboration with the Guidelines Working Group Members = from=20 CDC, the Infectious Disease Society of America, and the American = Society=20 of Blood and Marrow Transplantation

Additional Contributors

Summary

INTRODUCTION

Using These Guidelines

BACKGROUND

Immune System Recovery After HSCT

Opportunistic Pathogens After HSCT

BACTERIAL INFECTIONS

General Recommendations

Recommendations Regarding Stre. pneumoniae

Recommendations Regarding Streptococci viridans =

Recommendations Regarding Ha. influenzae type b =

VIRAL INFECTIONS

Recommendations Regarding Cytomegalovirus

Recommendations Regarding EBV

Recommendations Regarding HSV

Recommendations Regarding VZV

Recommendations Regarding CRV Infections: Influenza, = Respiratory=20 Syncytial Virus, Parainfluenza Virus, and Adenovirus

FUNGAL INFECTIONS

General Recommendations

Recommendations Regarding Yeast Infections

Recommendations Regarding Mold Infections

PROTOZOAL AND HELMINTHIC INFECTIONS

Recommendations Regarding PCP

Recommendations Regarding Toxoplasma gondii =

Recommendations Regarding Strongyloides = stercoralis=20

Recommendations Regarding Trypanosoma cruzi =

HOSPITAL INFECTION CONTROL

Room Ventilation

Construction, Renovation, and Building Cleaning

Isolation and Barrier Precautions

Hand Hygiene

Equipment

Plants, Play Areas, and Toys

HCWs

HSCT Center Visitors

Patient Skin and Oral Care

Preventing Bacterial Intravascular Catheter-Related = Infections=20

Control of Specific Nosocomial Infections

Infection Control Surveillance

STRATEGIES FOR SAFE LIVING AFTER HSCT -- PREVENTING = EXPOSURE AND=20 DISEASE

Avoiding Environmental Exposures

Safe Sex

Pet Safety

Water and Other Beverage Safety

Food Safety

Travel Safety

HSCT RECIPIENT VACCINATIONS

HEMATOPOIETIC STEM CELL SAFETY

Preventing Transmission of Infections from HSCT Donors to=20 Recipients

Pediatric Donors

Preventing Infection from Extraneous Contamination of = Donated=20 Units

In Utero or Fetal HSCT

Acknowledgments

References

Introduction

Background

Bacterial Infections

Viral Infections

Fungal Infections

Protozoal and Helminthic Infections

Hospital Infection Control

Strategies for Safe Living After HSCT -- Prevention of = Exposure and=20 Disease

HSCT Recipient Vaccinations

Hematopoietic Stem Cell Safety

Appendix

Dosing Charts for Preventing Opportunistic Infections Among=20 Hematopoietic Stem Cell Transplant Recipients

**Recommendations Regarding Ha. influenzae type b** =