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Antimicrobial Prophylaxis in Hematopoietic Stem Cell Transplant Recipients - Adult/Pediatric - Inpatient/Ambulatory

Antimicrobial Prophylaxis in Hematopoietic Stem Cell Transplant Recipients - Adult/Pediatric - Inpatient/Ambulatory - Clinical Hub, UW Health Clinical Tool Search, UW Health Clinical Tool Search, Clinical Practice Guidelines, Oncology


1
Antimicrobial Prophylaxis in Hematopoietic
Stem Cell Transplant Recipients –
Adult/Pediatric – Inpatient/Ambulatory
Clinical Practice Guideline
Note: Active Table of Contents – Click to follow link
EXECUTIVE SUMMARY .............................................................................................................................. 3
KEY PRACTICE RECOMMENDATIONS ..................................................................................................... 3
SCOPE .......................................................................................................................................................... 5
METHODOLOGY .......................................................................................................................................... 6
DEFINITIONS ............................................................................................................................................... 6
INTRODUCTION ........................................................................................................................................... 6
RECOMMENDATIONS ................................................................................................................................. 8
UW HEALTH IMPLEMENTATION ............................................................................................................. 17
APPENDIX A: ANTIMICROBIAL PROPHYLAXIS ALGORITHMS .......................................................... 19
FIGURE 1. ADULT ANTIBACTERIAL PROPHYLAXIS ............................................................................ 19
FIGURE 2. ADULT PNEUMOCOCCAL PROPHYLAXIS .......................................................................... 20
FIGURE 3. ADULT ALLOGENEIC ANTIFUNGAL PROPHYLAXIS ......................................................... 21
FIGURE 4. PEDIATRIC ALLOGENEIC ANTIFUNGAL PROPHYLAXIS .................................................. 22
FIGURE 5. ADULT AUTOLOGOUS ANTIFUNGAL PROPHYLAXIS ....................................................... 23
FIGURE 6. PEDIATRIC AUTOLOGOUS ANTIFUNGAL PROPHYLAXIS ................................................ 24
FIGURE 7. ADULT AND PEDIATRIC ALLOGENEIC PJP PROPHYLAXIS ............................................ 25
FIGURE 8. ADULT AND PEDIATRIC AUTOLOGOUS PJP PROPHYLAXIS .......................................... 26
FIGURE 9. ADULT AND PEDIATRIC HSV/VZV PROPHYLAXIS ............................................................. 27
FIGURE 10. ADULT ALLOGENEIC CMV PROPHYLAXIS ....................................................................... 28
FIGURE 11. PEDIATRIC ALLOGENEIC CMV PROPHYLAXIS ............................................................... 29
FIGURE 12. ADULT AUTOLOGOUS CMV PROPHYLAXIS .................................................................... 30
FIGURE 13. PEDIATRIC AUTOLOGOUS CMV PROPHYLAXIS ............................................................. 31
APPENDIX B. EVIDENCE GRADING SCHEMES ..................................................................................... 32
REFERENCES ............................................................................................................................................ 33
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Contact for Content:
Name: Philip Trapskin, PharmD, BCPS – Manager, Drug Policy Program
Phone Number: (608) 263-1328
Email Address: ptrapskin@uwhealth.org

Contact for Changes:
Name: Mary Mably, RPh, BCOP – Pharmacy
Phone Number: (608) 263-1263
Email Address: mmably@uwhealth.org

Guideline Authors:
Rupal Jaffa, PharmD
Mary Mably, RPh, BCOP
Sara Koth, PharmD, BCOP
Nicole Lubcke, PharmD, BCOP
Lucas Schulz, PharmD, BCPS (AQ-ID)

Coordinating Team Members:
Joshua Vanderloo, PharmD, BCPS; Drug Policy Program

Review Individuals/Bodies:
Barry Fox, MD – Adult Infectious Diseases
Aric Hall, MD – Adult Bone Marrow Transplant
Sheryl Henderson, MD – Pediatric Infectious Diseases
Inga Hofmann, MD – Pediatric Bone Marrow Transplant
Mark Juckett, MD – Adult Bone Marrow Transplant
Alex Lepak, MD – Adult Infectious Diseases

Committee Approvals/Dates:
Adult and Pediatric Bone Marrow Transplant Committee – February 2017
Transplant Infectious Diseases Committee – March 2017
Antimicrobial Use Subcommittee – March 2017
Pharmacy & Therapeutics Committee – May 2017

Release Date: May 2017 | Next Review Date: May 2019


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Executive Summary
Guideline Overview
This document is intended to guide clinicians in screening adult and pediatric hematopoietic stem cell
transplant patients for select infectious complications and assist in the selection of optimal antimicrobial
prophylaxis agents for these patients.

Key Practice Recommendations

Antibacterial Prophylaxis
1. Adult allogeneic and autologous patients
1.1. Antibacterial prophylaxis with oral levofloxacin should begin on day 0 and continue for the
duration of neutropenia or until first fever. 1-9 See Figure 1. (UW Health Strong
Recommendation, High Quality of Evidence) Dosing and additional detailed information is
available in the detailed recommendations.
1.2. Pneumococcal prophylaxis with penicillin VK should begin at day +90 and continue until at
least day +365 in allogeneic transplant patient with hypogammaglobulinemia and should
begin with the onset of systemic immunosuppression until it is stopped in patients with
chronic graft versus host disease. 1,2,10 See Figure 2. (UW Health Strong Recommendation,
Low Quality of Evidence) Dosing and additional detailed information is available in the
detailed recommendations.

2. Pediatric autologous and allogeneic patients
2.1. Antibacterial prophylaxis is not recommended for pediatric transplant recipients.1 (UW Health
Moderate Recommendation, Low Quality of Evidence)
2.2. Pneumococcal prophylaxis with penicillin VK should begin at day +90 and continue until at
least day +365 in select allogeneic transplant patients.1,2,10 (UW Health Strong
Recommendation, Low Quality of Evidence)

Antifungal prophylaxis
1. Adult and pediatric allogeneic patients
1.1. Antifungal prophylaxis should be based on risk factors and begin with day 0 and continue
until day +100.1,2,11-13 See Figure 3 (Adult) and Figure 4 (Pediatric). (UW Health Strong
Recommendation, High Quality of Evidence) Dosing and additional detailed information is
available in the detailed recommendations.
2. Adult and pediatric autologous patients
2.1. Adult patients with a history of invasive fungal infection should receive antifungal prophylaxis
with posaconazole from day 0 until cessation of therapy is determined to be clinically
appropriate.2,14,15 See Figure 5. (UW Health Strong Recommendation, Low Quality of
Evidence) Dosing and additional detailed information is available in the detailed
recommendations.
2.2. High risk pediatric patients without a history of invasive fungal infection should receive
antifungal prophylaxis with oral fluconazole from day 0 until resolution of neutropenia.1,2,11-13
See Figure 6. (UW Health Strong Recommendation, Low Quality of Evidence) Dosing and
additional detailed information is available in the detailed recommendations.

PJP Prophylaxis
1 Adult and pediatric allogeneic patients
1.1 PJP prophylaxis with sulfamethoxazole/trimethoprim should begin at the time of engraftment
and continue for at least six months after transplant and for the duration of
immunosuppression.1,2,16-23 See Figure 7. (UW Health Strong Recommendation, High Quality
of Evidence) Dosing and additional detailed information is available in the detailed
recommendations.
2 Adult and pediatric autologous patients
2.1 PJP prophylaxis for all autologous patients should begin at the time of engraftment and
continue for at least three months after transplant.1,2,24-26 See Figure 8. (UW Health Strong
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Recommendation, Low Quality of Evidence) Dosing and additional detailed information is
available in the detailed recommendations.

HSV/VZV Prophylaxis
1. Adult and pediatric allogeneic and autologous patients
1.1. HSV prophylaxis with oral acyclovir should begin with the conditioning regimen and continue
for at least one year after transplant in all HSV seropositive patients.1,2,27-32 See Figure 9.
(UW Health Strong Recommendation, Low Quality of Evidence) Dosing and additional
detailed information is available in the detailed recommendations.
1.2. In patients who are seropositive for VZV, VZV prophylaxis should begin with the conditioning
regimen and continue for at least one year after transplant. (UW Health Strong
Recommendation, Low Quality of Evidence)

CMV Prophylaxis
1. Adult and pediatric allogeneic patients: See Figure 10 (Adult) and Figure 11 (Pediatric). Dosing and
additional detailed information is available in the detailed recommendations.
1.1. Patients without a history of CMV disease who are seropositive for CMV or have a CMV
seropositive donor should receive weekly CMV screening by PCR from day +10 until day
+100. Treatment for CMV maybe initiated after a single positive blood PCR.1,2 (UW Health
Strong Recommendation, Low Quality of Evidence)
1.2. Weekly screening after day +100 can be considered in patients who are at high risk for late
CMV disease, with treatment initiated after two positive CMV PCRs or if clinically indicated.
1.3. All patients with a history of CMV disease prior to transplant should receive prophylactic
therapy with valganciclovir from engraftment until day +100.1,33 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
1.4. In patients who have myelosuppression (ANC fewer than 1000 or platelets less than 25000)
thought to be due to ganciclovir or valganciclovir, consider holding therapy.1,2,34 (UW Health
Strong Recommendation, Moderate Quality of Evidence)
2. All CMV seropositive patients receiving a cord blood transplant should receive prophylactic therapy
beginning on day 14 and continuing for at least 3 months and for the duration of systemic
immunosuppression.(UW Health Strong Recommendation, Very Low Quality of Evidence)
2.1. High dose oral valacyclovir is the first line agent to be started at day 14 and continued until
engraftment as defined by an ANC greater than 2000 cells/mcL and platelet count greater
than 80000 cells/mcL for 3 days.
3. Adult and pediatric autologous patients: See Figure 12 (Adult) and Figure 13 (Pediatric). Dosing and
additional detailed information is available in the detailed recommendations.
3.1. All CMV seropositive patients who have a history of CMV disease should receive
prophylactic therapy with valganciclovir from engraftment until day +100 (UW Health Strong
Recommendation, Very Low Quality of Evidence)1,33
3.2. Patients without a history of CMV disease, who are seropositive and at high risk should
receive weekly screening from day +10 to day +100, with treatment for CMV initiated after a
single positive PCR.
3.3. In patients without a history of CMV disease who are not at high risk, no screening or
prophylaxis is required.1,2 (UW Health Weak Recommendation, Very Low Quality of
Evidence)
3.4. In patients who have myelosuppression (ANC fewer than 1000 or platelets fewer than 25000)
thought to be due to ganciclovir or valganciclovir, consider holding therapy.1,2,34 (UW Health
Strong Recommendation, Moderate Quality of Evidence)
4. Treatment for patients with positive CMV PCR
4.1. Ganciclovir is the preferred first line agent for the treatment of CMV infection1,2,34 (UW Health
Strong Recommendation, Moderate Quality of Evidence)
4.2. In patients with adequate oral intake and absorption, valganciclovir may be used.1,2,33,35-38
(UW Health Strong Recommendation, High Quality of Evidence)
4.3. In patients who have persistent CMV viremia despite several weeks of treatment with
ganciclovir or valganciclovir, ganciclovir-resistant CMV should be considered and a CMV
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resistance panel should be checked. (UW Health Strong Recommendation, Very Low Quality
of Evidence)
4.4. Treatment for CMV should be continued for at least two weeks and until CMV PCR is no
longer detectable.1,2 (UW Health Strong Recommendation, Very Low Quality of Evidence)
4.5. In patients who have myelosuppression (ANC fewer than 1000 or platelets fewer than 25000)
thought to be due to ganciclovir or valganciclovir, consider holding therapy.1,2,34 (UW Health
Strong Recommendation, Moderate Quality of Evidence)

RSV Prophylaxis
1. Pediatric autologous and allogeneic patients
1.1. Palivizumab may be considered in pediatric patients younger than 2 years of age who
undergo HSCT between November and April.1,33 (UW Health Weak Recommendation, Very
Low Quality of Evidence)
1.2. No prophylaxis is recommended in patients over the age of 2 years.1,2 (UW Health Weak
Recommendation, Very Low Quality of Evidence)
1.3. Refer to Palivizumab – Pediatric/Neonatal – Inpatient/Ambulatory Clinical Practice Guideline.

HBV Prophylaxis
1. Refer to Hepatitis B Prophylaxis for Non-Thoracic Solid Organ Transplant – Adult – Inpatient Clinical
Practice Guideline

Companion Documents
1. Management of Neutropenic Fever – Adult – Inpatient/Ambulatory Clinical Practice Guideline
2. Palivizumab – Pediatric/Neonatal – Inpatient/Ambulatory Clinical Practice Guideline
3. Intravenous Immunoglobulin (IVIG) – Adult/Pediatric – Inpatient/Ambulatory Clinical Practice
Guideline
4. Renal Function-Based Dose Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline
5. Chronic Graft-Versus-Host Disease Diagnosis and Treatment – Adult – Inpatient/Ambulatory Clinical
Practice Guideline
6. Influenza and Pneumococcal Vaccination – Adult/Pediatric – Inpatient/Ambulatory
7. Hepatitis B Prophylaxis for Non-Thoracic Solid Organ Transplant – Adult – Inpatient Clinical Practice
Guideline
Scope
Disease/Condition: Adult and pediatric patients receiving hematopoietic stem cell transplant

Clinical Specialty: Bone Marrow Transplant, Infectious Diseases, Pharmacy

Intended Users: Physicians, advanced practice providers, pharmacists

Objective: To provide clinicians guidance in screening adult and pediatric hematopoietic stem cell
transplant patients for infectious complications and assist in the selection of antimicrobial prophylaxis.

Target Population: Adult and pediatric patients who have received a hematopoietic stem cell transplant

Interventions and Practices Considered:
ξ Screening for included infectious diseases
ξ Prophylactic therapy for included infectious diseases
ξ Treatment regimens for positive screening tests

Major Outcomes Considered:
ξ Prevention of bacterial, fungal, and viral infections among hematopoietic stem cell transplant
patients
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Methodology
Methods Used to Collect/Select the Evidence:
Electronic database searches (e.g., PUBMED) were conducted by the guideline authors and workgroup
members to collect evidence for review. Expert opinion and clinical experience were also considered
during discussions of the evidence.

Methods Used to Formulate the Recommendations:
The workgroup members agreed to adopt recommendations developed by external organizations and/or
arrived at a consensus through discussion of the literature and expert experience. All recommendations
endorsed or developed by the guideline workgroup were reviewed and approved by other stakeholders or
committees.

Methods Used to Assess the Quality of the Evidence/Strength of the Recommendations:
Internally developed recommendations, or those adopted from external sources without an assigned
evidence grade, were evaluated by the guideline workgroup using an algorithm adapted from the Grading
of Recommendations Assessment, Development and Evaluation (GRADE) methodology (see Figure 1 in
Appendix B).

Rating Scheme for the Strength of the Evidence/Recommendations:
See Appendix B for the rating schemes used within this document.

Recognition of Potential Health Care Disparities: African Americans receiving hematopoietic stem cell
transplants have significantly worse overall survival and disease free survival compared with
Caucasians.45 Appropriate prophylaxis against infectious diseases can help improve overall survival in all
patients.
Definitions
ξ ANC: absolute neutrophil count
ξ CMV: cytomegalovirus
ξ CMV disease: invasive CMV infection, including but not limited to CMV pneumonitis or enteritis
ξ HBV: hepatitis B virus
ξ HSV: herpes simplex virus
ξ IVIG: intravenous immunoglobulin
ξ PJP: Pneumocystis jiroveci pneumonia
ξ VZV: varicella zoster virus
ξ RSV: respiratory syncytial virus
ξ Fever: Oral temperature greater than or equal to 38.3ºC (101ºF) or a sustained oral temperature
of greater than or equal to 38ºC (100.4 ºF) for at least one-hour
ξ Neutropenia: Absolute neutrophil count (ANC) fewer than 500 cells/mm3 or an ANC expected to
decline to fewer than 500 cells/mm3 within the next 48 hours
ξ Day 0: day of stem cell infusion
ξ PCV13: pneumococcal conjugate vaccine 13 valent
ξ PPSV23: pneumococcal polysaccharide vaccine 23 valent
Introduction
Hematopoietic stem cell transplant (HSCT) patients are at increased risk for a variety of infections
due to the high levels of immunosuppression required to allow for transplantation. The duration of this
immunosuppression is generally thought to be 24 months following transplant if the patient is not
otherwise immunosuppressed and does not experience graft versus host disease.1,2 Allogeneic
transplant patients are at higher risk for infectious diseases than those receiving autologous transplant,
although infectious disease is still a leading cause of death in both populations, comprising 7% of deaths
after autologous transplant and 17% of deaths after unrelated allogeneic donor transplant.46
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The most recent guidelines from the American Society for Blood and Marrow Transplantation
(ASBMT) and the Infectious Diseases Society of America (IDSA) published in 2009 suggest a variety of
preventative strategies to reduce the risk of a variety of infections in HSCT patients, with an emphasis on
the use of antimicrobial agents for bacterial, viral, and fungal prophylaxis.1
Multiple studies demonstrate that appropriate antibacterial prophylaxis reduces the incidence of
febrile neutropenia, documented bacterial infection, and bloodstream infections in the HSCT population,
with one study showing a decrease in rates of febrile neutropenia from 91% to 60% with the addition of
levofloxacin prophylaxis.47,48 Additionally, retrospective analysis at UW Health showed a non-significant
decrease in rates of febrile neutropenia with fluoroquinolone prophylaxis and no increase in the rates of
Clostridium difficile infection or drug resistance.49
A 2014 meta-analysis demonstrated a decrease in invasive fungal infections to approximately 5%
when HSCT patients received antifungal prophylaxis with fluconazole or amphotericin B. 50
Viral infections are also prevalent in the HSCT population, with 80% of CMV positive allogeneic
HSCT recipients and 40% of CMV positive autologous HSCT recipients developing a CMV infection after
transplant. Following the use of antiviral agents to prevent the reactivation of the virus, disease rates
dropped significantly, with only 20-35% of allogeneic transplant recipients developing disease.51 Thus,
the use of antimicrobial prophylaxis agents can significantly reduce the risk of infectious disease in both
allogeneic and autologous HSCT patients.
Despite the availability of guidelines encouraging the use of antimicrobial prophylaxis and clinical
evidence demonstrating the benefits of its use, strategies vary widely across centers and many patients
do not receive optimal prophylaxis against infectious diseases.52 To ensure that HSCT patients receive
adequate infectious disease prophylaxis, the Foundation for the Accreditation of Cellular Therapy and the
Joint Accreditation Committee-ISCT and EBMT (FACT-JACIE) requires that all clinical programs have
current practice guidelines related to infection prevention.1 The creation of a single clinical practice
guideline for the prevention of infectious diseases in HSCT patients will allow for compliance with FACT-
JACIE requirements for accreditation and will standardize care and ensure that all patients are receiving
optimal prophylactic therapy.

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Recommendations
1. Antibacterial Prophylaxis
1.1. Adult allogeneic and autologous patients. See Figure 1.
1.1.1. Antibacterial prophylaxis with oral levofloxacin should begin on day 0 and continue for
the duration of neutropenia or until first fever.1-9 (UW Health Strong Recommendation,
High Quality of Evidence)
1.1.1.1. Patients unable to tolerate levofloxacin may receive cefpodoxime.53 (UW
Health Strong Recommendation, Low Quality of Evidence)
1.1.1.2. In patients unable to take oral agents (Grade 3 mucositis or higher), use of an
IV formulation is recommended. (UW Health Strong Recommendation, Low
Quality of Evidence)
1.1.1.3. Prophylaxis should be discontinued if the patient develops fever attributed to
bacterial infection and neutropenic fever treatment is initiated.5,6,8,9,54 (UW
Health Strong Recommendation, High Quality of Evidence) (refer to
Management of Neutropenic Fever – Adult – Inpatient Clinical Practice
Guideline)
1.1.2. In patients with IgG below 400 mg/dL, intravenous immunoglobulin (IVIG) at 500
mg/kg/week based on ideal body weight may be considered.1 (UW Health Weak
Recommendation, Very Low Quality of Evidence) (refer to Intravenous Immunoglobulin
(IVIG) – Adult/Pediatric – Inpatient/Ambulatory Clinical Practice Guideline)
1.1.2.1. In patients receiving IVIG, IgG blood concentrations should be checked at
least every 4 weeks.1 (UW Health Weak Recommendation, Very Low Quality
of Evidence)
1.1.3. Pneumococcal prophylaxis. See Figure 2.
1.1.3.1. Pneumococcal prophylaxis with penicillin VK should begin at day +90 and
continue until at least day +365 for allogeneic transplant patients with
hypogammaglobulinemia.1,2,10 (UW Health Strong Recommendation, Low
Quality of Evidence)
1.1.3.1.1. In patients who are unable to receive penicillin prophylaxis, oral
azithromycin may be considered.55-57 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
1.1.3.2. Pneumococcal prophylaxis for allogeneic transplant patients with chronic
GVHD should begin at the onset of GVHD and continue until all
immunosuppression has been discontinued.1,2 (UW Health Strong
Recommendation, Low Quality of Evidence) (refer to Chronic Graft-Versus-
Host Disease Diagnosis and Treatment – Adult – Inpatient/Ambulatory Clinical
Practice Guideline)
1.1.3.2.1. In GVHD patients receiving azithromycin as part of GVHD therapy,
no additional prophylaxis is needed.55-57 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
1.1.3.2.2. In GVHD patients who are not receiving azithromycin as part of
GVHD therapy, penicillin VK is the preferred agent for
pneumococcal prophylaxis.1,2,10,55-57 (UW Health Strong
Recommendation, Very Low Quality of Evidence)

Table 1: Adult Dosing of Prophylactic Antibacterial AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Levofloxacin 500 mg daily Oral, IV
Cefpodoxime 200 mg twice daily Oral
Penicillin VK 250 mg twice daily Oral
Azithromycin 250 mg Monday/Wednesday/Friday Oral
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline)
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1.2. Pediatric autologous and allogeneic patients
1.2.1. Antibacterial prophylaxis is not recommended for pediatric transplant recipients.1 (UW
Health Weak Recommendation, Low Quality of Evidence)
1.2.2. In allogeneic transplant recipients with IgG below 400 mg/dL, IVIG 400 mg/kg/month
may be considered, with serum IgG levels checked every 3-4 weeks.1 (UW Health
Weak Recommendation, Very Low Quality of Evidence)
1.2.3. Pneumococcal prophylaxis
1.2.3.1. Pneumococcal prophylaxis with penicillin VK should begin at day +90 and
continue until at least day +365 for allogeneic transplant patients with
hypogammaglobulinemia.1,2,10 (UW Health Strong Recommendation, Low
Quality of Evidence)
1.2.3.1.1. In patients who are unable to receive penicillin prophylaxis, oral
azithromycin may be considered.55-57 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
1.2.3.2. Pneumococcal prophylaxis for allogeneic transplant patients with chronic
GVHD should begin at day +90 and continue until all immunosuppression has
been discontinued.1,2 (UW Health Strong Recommendation, Low Quality of
Evidence) (refer to Chronic Graft-Versus-Host Disease Diagnosis and
Treatment – Adult – Inpatient/Ambulatory)
1.2.3.2.1. In GVHD patients receiving azithromycin as part of GVHD
therapy, no additional prophylaxis is needed.55-57 (UW Health
Strong Recommendation, Very Low Quality of Evidence)
1.2.3.2.2. In GVHD patients who are not receiving azithromycin as part of
GVHD therapy, penicillin VK is the preferred agent for
pneumococcal prophylaxis.1,2,10,55-57 (UW Health Strong
Recommendation, Very Low Quality of Evidence)

Table 2: Pediatric Dosing of Prophylactic Antibacterial AgentsA
Medication Prophylaxis Dose
Penicillin VK < 3 years: 125 mg twice daily
≥ 3 years: 250 mg twice daily
Azithromycin 10 mg/kg daily on Monday/ Wednesday/Friday (max: 250 mg)
A
Medications may require dose adjustment based on renal function

2. Antifungal prophylaxis
2.1. Adult and pediatric allogeneic patients. See Figure 3 (Adult) and Figure 4 (Pediatric).
2.1.1. Antifungal prophylaxis should begin at day 0 and continue until day +100.1,2,11,12 (UW
Health Strong Recommendation, High Quality of Evidence)
2.1.2. Fluconazole is the recommended first-line agent for patients without a history of
invasive fungal infection or GVHD and who are not receiving a haploidentical or T-cell
depleted transplant.2,13,58-62 (UW Health Strong Recommendation, High Quality of
Evidence)
2.1.2.1. For hospitalized patients who have are unable to tolerate fluconazole
prophylaxis, have a contraindication to fluconazole, or have significant drug
interactions with azole agents, micafungin is the first-line alternative
agent.2,59,63,64 (UW Health Strong Recommendation, Moderate Quality of
Evidence)
2.1.2.2. Hospitalized adult patients and pediatric patients over the age of 13 receiving
micafungin due to fluconazole intolerance or contraindication should be
transitioned to posaconazole extended release tablets when able,
approximately one week prior to discharge. (UW Health Weak
Recommendation, Low Quality of Evidence)
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2.1.2.3. Ambulatory patients over the age of 13 years who are unable to tolerate
fluconazole prophylaxis and inpatients who have failed both fluconazole and
micafungin may be started on oral posaconazole extended release
tablets.2,59,65,66 (UW Health Weak Recommendation, Moderate Quality of
Evidence)
2.1.3. In patients over the age of 13 who have a history of invasive fungal infection,
posaconazole extended release tablets are the first line agent for prophylaxis.2,65 (UW
Health Strong Recommendation, Moderate Quality of Evidence)
2.1.4. In patients over the age of 13 receiving a haploidentical, cord blood, or T-cell depleted
transplant, posaconazole extended release tablets are the first line agent for
prophylaxis. (UW Health Strong Recommendation, Very Low Quality of Evidence)
2.1.5. In patients over the age of 13 years with GVHD receiving prednisone doses greater
than or equal to 20 mg per day (or equivalent steroid doses) or dual systemic
immunosuppressive therapies, posaconazole is recommended as the first line
agent.2,59,65 (UW Health Strong Recommendation, Moderate Quality of Evidence) (refer
to Chronic Graft-Versus-Host Disease Diagnosis and Treatment – Adult –
Inpatient/Ambulatory Clinical Practice Guideline)
2.1.5.1. In patients who are unable to obtain or tolerate posaconazole, voriconazole
should be considered.2,66 (UW Health Strong Recommendation, Moderate
Quality of Evidence)
2.1.6. In patients younger than 13 years of age with GVHD, voriconazole is recommended
from the time of diagnosis until resolution of GVHD.59,66 (UW Health Weak
Recommendation, Low Quality of Evidence)
2.1.6.1. In patients who are unable to obtain or tolerate voriconazole, micafungin
should be considered. (UW Health Strong Recommendation, Very Low
Quality of Evidence)
2.1.7. Voriconazole is an acceptable alternative to posaconazole in patients who are unable
to obtain posaconazole.2,66 (UW Health Strong Recommendation, Moderate Quality of
Evidence)
2.1.8. In adult patients who are unable to use fluconazole, posaconazole, or voriconazole,
isavuconazole may be considered. (UW Health Weak Recommendation, Very Low
Quality of Evidence)
2.2. Adult and pediatric autologous patients. See Figure 5 (Adult) and Figure 6 (Pediatric).
2.2.1. Adult and pediatric patients over the age of 13 years with a history of invasive fungal
infection should receive antifungal prophylaxis with posaconazole from day 0 until
cessation of posaconazole therapy is determined to be clinically appropriate.2,14,15 (UW
Health Strong Recommendation, Low Quality of Evidence)
2.2.2. Pediatric patients under the age of 13 with a history of invasive fungal infection should
receive antifungal prophylaxis with voriconazole from day 0 until cessation of
voriconazole therapy is determined to be clinically appropriate. (UW Health Strong
Recommendation, Low Quality of Evidence)
2.2.3. Patients without a history of invasive fungal infection should receive antifungal
prophylaxis with oral fluconazole from day 0 until resolution of neutropenia.2,58,67 (UW
Health Strong Recommendation, Low Quality of Evidence)
2.2.4. IV therapy with micafungin may be considered in patients who cannot tolerate oral
fluconazole.2,63 (UW Health Strong Recommendation, Moderate Quality of Evidence)
2.3. Therapeutic drug monitoring and administration considerations of azoles
2.3.1. Fluconazole
2.3.1.1. Therapeutic drug monitoring of fluconazole is not recommended due to
predictable kinetics.2,68-72
2.3.2. Posaconazole
2.3.2.1. Posaconazole delayed release tablets are the preferred dosage formulation
due to improved absorption.2,73,74 (UW Health Strong Recommendation, High
Quality of Evidence)
2.3.2.2. If patients are unable to obtain delayed release tablets, posaconazole
suspension may be considered, with consideration given to administration
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requirements of the suspension (Posaconazole HFFY).2,73,74 (UW Health
Strong Recommendation, High Quality of Evidence)
2.3.2.3. Posaconazole monitoring may be considered after one week of treatment,
with a target trough concentration greater than 0.7 mcg/mL for prophylaxis.2,75-
77
(UW Health Weak Recommendation, Low Quality of Evidence)
2.3.3. Voriconazole
2.3.3.1. Voriconazole monitoring may be considered after one week of treatment, with
target trough greater than 0.5 mcg/mL for prophylaxis.2,78-80 (UW Health
Strong Recommendation, Moderate Quality of Evidence)
2.3.4. Isavuconazole
2.3.4.1. Therapeutic drug monitoring of isavuconazole is not recommended.2 (UW
Health Strong Recommendation, Very Low Quality of Evidence)

Table 3: Adult Dosing of Prophylactic Antifungal AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Fluconazole 400 mg daily Oral, IV
Micafungin 50 mg daily IV
Posaconazole
*Use extended release tablet
formulation
300 mg daily Oral, IV
Voriconazole 200 mg twice daily Oral, IV
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline Clinical Practice Guideline)

Table 4: Pediatric Dosing of Prophylactic Antifungal AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Fluconazole 6 mg/kg/day (max 400 mg) Oral
Posaconazole
*Use extended release tablet
formulation
≥13 years: 300mg daily Oral
Posaconazole suspension
*Must be given with 15 g of fat
≥13 years: 4mg/kg three times daily (max
200 mg per dose) Oral
Voriconazole
< 20 kg: 50 mg twice daily
20-40 kg: 100 mg twice daily
>40 kg: 200 mg twice daily
Oral, IV
Micafungin 3mg/kg (max 50mg) IV
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function

3. PJP Prophylaxis
3.1. Adult and pediatric allogeneic patients. See Figure 7.
3.1.1. PJP prophylaxis with sulfamethoxazole/trimethoprim should begin at the time of
engraftment and continue for at least six months after transplant and for the duration of
immunosuppression.1,2,16-23 (UW Health Strong Recommendation, High Quality of
Evidence)
3.1.2. In patients with severe reactions to sulfamethoxazole/trimethoprim, desensitization to
sulfamethoxazole/trimethoprim is the preferred strategy.1,2,81 (UW Health Strong
Recommendation, Low Quality of Evidence)
3.1.3. In patients unable to be desensitized to sulfamethoxazole/trimethoprim acceptable
alternatives, listed in order of preference, are atovaquone, dapsone, inhaled
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pentamidine, and intravenous pentamidine.1,2,82-86 (UW Health Weak Recommendation,
Moderate Quality of Evidence)
3.1.4. Sulfamethoxazole/trimethoprim may cause pancytopenia and discontinuation may be
considered for ANC fewer than 1000 cells/mcL or platelets fewer than 30,000
cells/mcL. (UW Health Weak Recommendation, Low Quality of Evidence)
3.1.4.1. Risk of pancytopenia from sulfamethoxazole/trimethoprim may be reduced by
adding folic acid 1 mg daily. (UW Health Weak Recommendation, Low Quality
of Evidence)
3.1.5. Patients being started on dapsone should be tested for G6PD deficiency, and an
alternative agent used if deficiency is detected.2,55 (UW Health Strong
Recommendation, Moderate Quality of Evidence)
3.2. Adult and pediatric autologous patients. See Figure 8.
3.2.1. PJP prophylaxis for all autologous patients should begin at the time of engraftment and
continue for at least three months after transplant.1,2,24-26 (UW Health Strong
Recommendation, Low Quality of Evidence)
3.2.2. Sulfamethoxazole/trimethoprim is the preferred agent for prophylaxis.1,2,20-23 (UW
Health Strong Recommendation, High Quality of Evidence)
3.2.3. In patients with severe reactions to sulfamethoxazole/trimethoprim, desensitization to
sulfamethoxazole/trimethoprim is the preferred strategy. (UW Health Weak
Recommendation, Very Low Quality of Evidence)
3.2.4. In patients unable to be desensitized to sulfamethoxazole/trimethoprim acceptable
alternatives, listed in order of preference, are atovaquone, dapsone, inhaled
pentamidine, and intravenous pentamidine.1,2,82-86 (UW Health Weak Recommendation,
Moderate Quality of Evidence)
3.2.5. Patients being started on dapsone should be tested for G6PD deficiency, and an
alternative agent used if deficiency is detected.2,55 (UW Health Strong
Recommendation, Moderate Quality of Evidence)

Table 5: Adult Dosing of PJP Prophylactic AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Sulfamethoxazole/trimethoprim 800/160 mg twice weekly Oral, IV
Atovaquone 1500 mg daily Oral
Dapsone 100 mg daily Oral
Pentamidine 300 mg monthly
300 mg monthly
Inhalation
IV
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline)


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Table 6: Pediatric Dosing of PJP Prophylactic AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Sulfamethoxazole/
trimethoprim 2.5 mg/kg twice daily x 2 days/week (max 800/160 mg) Oral, IV
Atovaquone
4 months- 24 months: 45 mg/kg daily (max 1500 mg)
2 – 13 years: 30 mg/kg daily (max 1500 mg)
≥ 13 years: 1500 mg daily
Oral
Dapsone 2 mg/kg daily (max 100 mg) Oral
Pentamidine > 10 years old: 300mg monthly Inhalation
Pentamidine 4 mg/kg monthly (max 300mg) IV
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline for adult dosing)

4. HSV/VZV Prophylaxis
4.1. Adult and pediatric allogeneic and autologous patients. See Figure 9.
4.1.1. HSV prophylaxis with oral acyclovir should begin with the conditioning regimen and
continue for at least one year after transplant in all patients.1,2,27-32 (UW Health Strong
Recommendation, Low Quality of Evidence)
4.1.2. In patients who are seropositive for VZV, including varicella vaccine recipients, VZV
prophylaxis with acyclovir should begin with the conditioning regimen and continue for
at least one year after transplant. (UW Health Strong Recommendation, Low Quality of
Evidence)
4.1.2.1. Valacyclovir may be considered as an alternative to acyclovir to reduce pill
burden. (UW Health Strong Recommendation, Very Low Quality of Evidence)
4.1.3. In allogeneic transplant patients who have GVHD or have had frequent reactivations of
HSV or VZV prior to transplantation, acyclovir prophylaxis should continue for at least
three months after discontinuation of all immunosuppressant medications.1,2,55,56,87 (UW
Health Strong Recommendation, Moderate Quality of Evidence)
4.1.4. In patients unable to tolerate oral therapy, IV acyclovir should be considered.1,2 (UW
Health Strong Recommendation, Low Quality of Evidence)
4.1.5. Patients receiving ganciclovir or valganciclovir for prevention or treatment of CMV do
not require additional prophylaxis against HSV and/or VZV.1,2,39,88 (UW Health Strong
Recommendation, Low Quality of Evidence)

Table 7: Adult Dosing of HSV/VZV Prophylactic AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Acyclovir (HSV dose) 400 mg twice daily Oral
Acyclovir (HSV dose) 200 mg every 12 hours IV
Acyclovir (VZV dose) 800 mg twice daily Oral
Acyclovir (VZV dose) 200 mg every 12 hours IV
Valacyclovir (VZV dose) 500 mg twice daily Oral
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline)


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Table 8: Pediatric Dosing of Prophylactic AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Acyclovir 30-40 mg/kg twice daily (max 400 mg/dose ) Oral
Acyclovir 250 mg/m2 every 12 hours (max 200 mg/dose) IV
Valacyclovir 15 mg/kg twice daily (max 500 mg/dose) Oral
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline for adult dosing)

5. CMV Prophylaxis
5.1. Adult and pediatric allogeneic patients. See Figure 10 (Adult) and Figure 11 (Pediatric).
5.1.1. Patients without a history of CMV disease who are seropositive for CMV or have a
CMV seropositive donor should receive weekly CMV screening by blood PCR from day
+10 until day +100. Treatment for CMV may be initiated after a single detectable PCR.
1,2
(UW Health Strong Recommendation, Low Quality of Evidence)
5.1.2. Patients receiving T-cell depleted transplants may be screened more frequently at the
discretion of the treating team. (UW Health Strong Recommendation, Very Low Quality
of Evidence)
5.1.3. Weekly screening after day +100 can be considered in patients who are at high risk for
late CMV disease, with treatment initiated after two detectable CMV PCRs or if
clinically indicated. Patients at high risk include those with at least one of the following
risk factors1,2,89,90: (UW Health Weak Recommendation, Low Quality of Evidence)
ξ GVHD patients
ξ Chronic steroid use (greater than 20 mg daily of prednisone)
ξ CD4+ less than 50 cells/mL or total lymphocyte count less than 100 cells/mL
ξ CMV D-/R+ transplant recipients
ξ Unrelated transplant
ξ Haploidentical transplant
ξ Cord blood transplant
ξ T-cell depleted transplant
5.1.4. Treatment for patients with positive or detectable CMV PCR
5.1.4.1. Ganciclovir is the preferred first line agent for the treatment of CMV
infection.1,2,34 (UW Health Strong Recommendation, Moderate Quality of
Evidence)
5.1.4.2. In patients with adequate oral intake and absorption, valganciclovir may be
used.1,2,33,35-38 (UW Health Strong Recommendation, High Quality of
Evidence)
5.1.4.3. In patients who have persistent CMV viremia despite several weeks of
treatment with ganciclovir or valganciclovir, ganciclovir-resistant CMV should
be considered and a CMV resistance panel should be checked. Infectious
Diseases service consultation should be strongly considered. (UW Health
Strong Recommendation, Very Low Quality of Evidence)
5.1.4.4. Foscarnet is the therapy of choice in patients with ganciclovir-resistant
CMV.1,2,34 (UW Health Strong Recommendation, Moderate Quality of
Evidence)
5.1.4.5. In patients who have myelosuppression (ANC fewer than 1000 or platelets
fewer than 25000 cells/mcL) thought to be due to ganciclovir or valganciclovir,
consider holding therapy or changing to foscarnet therapy.1,2,34 (UW Health
Strong Recommendation, Moderate Quality of Evidence)
5.1.4.6. Treatment for CMV should be continued for at least two weeks and until CMV
PCR is no longer detectable.1,2 (UW Health Strong Recommendation, Very
Low Quality of Evidence)
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5.1.5. All patients who have a history of CMV disease should receive prophylactic therapy
with valganciclovir from engraftment until day +100.1,33 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
5.1.5.1. Patients who are unable to tolerate oral prophylaxis may receive IV
ganciclovir.1,2,33,35-38 (UW Health Strong Recommendation, High Quality of
Evidence)
5.1.5.2. Patients who are unable to tolerate valganciclovir or ganciclovir may receive
high-dose valacyclovir. Pediatric patients must be greater than 40 kg to
receive valacyclovir.2,91 (UW Health Weak Recommendation, Low Quality of
Evidence)
5.1.5.3. In patients who have had two or more reactivations of CMV, indefinite therapy
with valganciclovir should be considered. (UW Health Weak
Recommendation, Very Low Quality of Evidence)
5.1.6. All CMV seropositive patients receiving a cord blood transplant should receive
prophylactic therapy beginning on day 14 and continuing for at least 3 months and for
the duration of systemic immunosuppression. (UW Health Strong Recommendation,
Very Low Quality of Evidence)
5.1.6.1. High-dose oral valacyclovir is the first line agent to be started at day 14 and
continued until engraftment as defined by an ANC greater than 2000
cells/mcL and platelet count greater than 80000 cells/mcL for 3 days.
5.1.6.1.1. High-dose IV acyclovir should be used in patients unable to
tolerate oral medications. (UW Health Strong Recommendation,
Very Low Quality of Evidence)
5.1.6.2. CMV seropositive cord blood transplant patients should be transitioned to
valganciclovir prophylaxis upon engraftment as defined above. (UW Health
Strong Recommendation, Very Low Quality of Evidence)
5.2. Adult and pediatric autologous patients. See Figure 12 (Adult) and Figure 13 (Pediatric).
5.2.1. All patients who have a history of CMV disease should receive prophylactic therapy
with valganciclovir from engraftment until day +100.1,33 (UW Health Strong
Recommendation, Very Low Quality of Evidence)
5.2.1.1. Patients who are unable to tolerate oral prophylaxis may receive IV
ganciclovir.1,2,33,35-38 (UW Health Strong Recommendation, High Quality of
Evidence)
5.2.1.2. Patients who are unable to tolerate valganciclovir or ganciclovir may receive
high-dose valacyclovir.2,91 (UW Health Weak Recommendation, Low Quality
of Evidence)
5.2.1.3. In patients who have had two or more reactivations of CMV, indefinite therapy
with valganciclovir should be considered. (UW Health Weak
Recommendation, Very Low Quality of Evidence)
5.2.2. Patients without a history of CMV disease, who are seropositive and at high risk
should receive weekly screening from day +10 to day +100. Treatment for CMV may
be initiated after a single positive PCR.
5.2.2.1. High risk patients include patients receiving purine analogs (fludarabine,
clofarabine, nelarabine, cladribine) in the last six months.1,2 (UW Health
Strong Recommendation, Low Quality of Evidence)
5.2.3. Treatment for patients with positive or detectable CMV PCR
5.2.3.1. Ganciclovir is the preferred first line agent for the treatment of CMV
infection.1,2,34 (UW Health Strong Recommendation, Moderate Quality of
Evidence)
5.2.3.2. In patients with adequate oral intake and absorption, valganciclovir may be
used.1,2,33,35-38 (UW Health Strong Recommendation, High Quality of
Evidence)
5.2.3.3. In patients who have persistent CMV viremia despite four weeks of treatment
with ganciclovir or valganciclovir, ganciclovir-resistant CMV should be
considered and a CMV resistance panel should be checked. (UW Health
Strong Recommendation, Very Low Quality of Evidence)
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5.2.3.4. Foscarnet is the therapy of choice in patients with ganciclovir-resistant CMV.
Infectious Diseases service consultation should be strongly considered.1,2,34
(UW Health Strong Recommendation, Moderate Quality of Evidence)
5.2.3.5. In patients who have myelosuppression thought to be due to ganciclovir or
valganciclovir, consider holding therapy or changing to foscarnet therapy.1,2,34
(UW Health Strong Recommendation, Moderate Quality of Evidence)
5.2.3.6. Treatment for CMV should be continued for at least two weeks and until CMV
PCR is no longer detectable.1,2 (UW Health Strong Recommendation, Very
Low Quality of Evidence)
5.2.4. In patients without a history of CMV disease who are not at high risk, no prophylaxis
is required.1,2 (UW Health Weak Recommendation, Very Low Quality of Evidence)

Table 9: Adult Dosing of CMV Prophylactic AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Valganciclovir 900 mg daily Oral
Ganciclovir 5 mg/kg IV
High-dose valacyclovir 2000 mg four times daily Oral
High-dose acyclovir 10 mg/kg every 8 hours (max 200 mg) IV
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline)

Table 10: Pediatric Dosing of CMV Prophylactic AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Valganciclovir Consult pharmacist for dosing Oral
Ganciclovir 5 mg/kg daily IV
High-dose valacyclovir ≥ 40 kg: 2000 mg four times daily Oral
High-dose acyclovir 500 mg/m2 every 8 hours (max 200 mg) IV
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline for adult dosing)

Table 11: Adult and Pediatric Dosing of CMV Treatment AgentsA,B
Medication Induction Dose Maintenance Dose
Ganciclovir 5 mg/kg twice daily x 14 days 5 mg/kg daily
Valganciclovir (adults only) 900 mg twice daily x 14 days 900 mg daily
Foscarnet 60 mg/kg every 8 hours x 14 days 90 mg/kg daily
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function (refer to Renal Function-Based Dose
Adjustments – Adult – Inpatient/Ambulatory Clinical Practice Guideline for adult dosing)

6. RSV Prophylaxis
6.1. Pediatric autologous and allogeneic patients
6.1.1. Palivizumab may be considered in pediatric patients less than 2 years of age who
undergo HSCT between November and April.1,33 (UW Health Weak Recommendation,
Very Low Quality of Evidence) (refer to Palivizumab – Pediatric/Neonatal –
Inpatient/Ambulatory Clinical Practice Guideline)
6.1.1.1. Palivizumab prophylaxis may be continued until: (UW Health Weak
Recommendation, Very Low Quality of Evidence)
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ξ A maximum of 5 doses have been administered;33,92
ξ The conclusion of RSV season;33,92 or
ξ Breakthrough RSV infection develops.33
6.1.2. Oral ribavirin may be considered as prophylaxis in pediatric patients who have been
exposed to RSV through sick contacts. (UW Health Weak Recommendation, Very Low
Quality of Evidence)
6.1.3. Inhaled ribavirin should not be used for RSV prophylaxis. (UW Health Strong
Recommendation, Very Low Quality of Evidence)
6.1.4. No prophylaxis is recommended in patients over the age of 2 years.1,2 (UW Health
Weak Recommendation, Very Low Quality of Evidence)

Table 12: Pediatric Dosing of Prophylactic AgentsA,B
Medication Prophylaxis Dose Dosage Forms
Palivizumab 15 mg/kg monthly IM
Ribavirin 5 mg/kg three times daily Oral
A Medications listed in order of preference
B
Medications may require dose adjustment based on renal function

7. HBV Prophylaxis
7.1. Refer to Hepatitis B Prophylaxis for Non-Thoracic Solid Organ Transplant – Adult – Inpatient
Clinical Practice Guideline
UW Health Implementation
Potential Benefits:
ξ Standardization of antimicrobial prophylaxis
ξ Reduction in rates of infection through improved screening

Potential Harms:
ξ Adverse reactions to suggested medications

Patient Resources
1. UW Health Posaconazole Health Facts for You

Guideline Metrics
1. Percentage of patients receiving appropriate antimicrobial prophylaxis
2. Percentage of patients being screened appropriately for CMV
3. Percentage of patients with CMV infection

Implementation Plan/Clinical Tools
1. Guideline will be posted on U-Connect in a dedicated location for Clinical Practice Guidelines.
2. Release of the guideline will be advertised in the Physician/APP Briefing newsletter.
3. Content and hyperlinks within clinical tools, documents, or Health Link related to the guideline
recommendations (such as the following) will be reviewed for consistency and modified as
appropriate.

Order Sets & Smart Sets
ξ IP – BMT – Allogeneic Stem Cell Transplant – Adult [1788]
ξ IP – BMT – Allogeneic Stem Cell Transplant – Adult – Post-Transplant Labs [1789]
ξ IP – BMT – Autologous Stem Cell Transplant – Adult – Admission [1821]
ξ IP – BMT – Autologous Stem Cell Transplant – Post-Transplant Labs [1822]
ξ IP – BMT – Myeloablative Umbilical Cord Blood – Adult – Post-Transplant Labs [2352]
ξ IP – BMT – Myeloablative Umbilical Cord Blood Transplant – Adult – Admission [2327]
ξ IP – BMT – Non-Ablative Allogeneic Stem Cell Transplant – Adult – Admission [2328]
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ξ IP – BMT – Non-Myeloablative Double Unit Umbilical Cord Blood Transplant – Adult – Admission
[2329]
ξ IP – BMT – Non-Myeloablative Umbilical Cord Blood Post Transplant Labs – Adult – Supplemental
[2351]
ξ IP – BMT – Adult – Discharge [4905]
ξ OP – Bone Marrow Transplant – CMV Screening – Adult – Clinic Visit [4798]
ξ OP – Day 100 Allogeneic Transplant Follow Up – Adult – Clinic Visit [5213]
ξ OP – Day 180 Allogeneic Transplant Follow Up – Adult – Clinic Visit [5214]
ξ OP – Day 270 Allogeneic Transplant Follow Up – Adult – Clinic Visit [5222]
ξ OP – Day 30 Allogeneic Transplant Follow Up – Adult – Clinic Visit [5005]
ξ OP – Day 60 Allogeneic Transplant Follow Up – Adult – Clinic Visit [5076]
ξ ANBL0532 Tandem HSCT #1 Thiotepa/cyclophosphamide for patients > 12kg [5687]
ξ ANBL0532 Tandem HSCT #2 (CEM) for patients > 12kg with altered renal function [5696]
ξ ANBL0532 Tandem HSCT #2 (CEM, GFR >= 100mL/min) for patients > 12 kg [5689]
ξ Cyclophosphamide(2D:-7,-6)/TBI(4D:-4,-3,-2-,1) [4903]
ξ Cyclophosphamide(2D:-6,-5)/TBI(3D:-3,-2-,1) [4953]
ξ SOC Busulfan-Cyclophosphamide [5692]
ξ Busulfan/Melphalan Conditioning Regimen [5765]
ξ Busulfan/Fludarabine/ATG Rabbit [5118]

Disclaimer
Clinical practice guidelines assist clinicians by providing a framework for the evaluation and treatment of
patients. This guideline outlines the preferred approach for most patients. It is not intended to replace a
clinician’s judgment or to establish a protocol for all patients. It is understood that some patients will not fit
the clinical condition contemplated by a guideline and that a guideline will rarely establish the only
appropriate approach to a problem.


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Appendix A: Antimicrobial Prophylaxis Algorithms
Figure 1. Adult Antibacterial Prophylaxis



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Figure 2. Adult Pneumococcal Prophylaxis





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Figure 3. Adult Allogeneic Antifungal Prophylaxis


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Figure 4. Pediatric Allogeneic Antifungal Prophylaxis



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Figure 5. Adult Autologous Antifungal Prophylaxis



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Figure 6. Pediatric Autologous Antifungal Prophylaxis


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Figure 7. Adult and Pediatric Allogeneic PJP Prophylaxis



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Figure 8. Adult and Pediatric Autologous PJP Prophylaxis




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Figure 9. Adult and Pediatric HSV/VZV Prophylaxis



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Figure 10. Adult Allogeneic CMV Prophylaxis


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Figure 11. Pediatric Allogeneic CMV Prophylaxis


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Figure 12. Adult Autologous CMV Prophylaxis


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Figure 13. Pediatric Autologous CMV Prophylaxis


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Appendix B. Evidence Grading Schemes

Figure 1. GRADE Methodology adapted by UW Health


GRADE Ranking of Evidence
High We are confident that the effect in the study reflects the actual effect.
Moderate We are quite confident that the effect in the study is close to the true effect, but it
is also possible it is substantially different.
Low The true effect may differ significantly from the estimate.
Very Low The true effect is likely to be substantially different from the estimated effect.

GRADE Ratings for Recommendations For or Against Practice
Strong The net benefit of the treatment is clear, patient values and circumstances
are unlikely to affect the decision.
Weak/conditional
Recommendation may be conditional upon patient values and
preferences, the resources available, or the setting in which the
intervention will be implemented.

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