Krüger, W.H., Bohlius, J., Cornely, O.A., Einsele, H., Hebart, H., Massenkeil, G., . . . Wolf, H.H. (2005). Antimicrobial prophylaxis in allogeneic bone marrow transplantation. Guidelines of the infectious diseases working party (AGIHO) of the German Society of Haematology and Oncology. Annals of Oncology, 16, 1381–1390.doi: 10.1093/annonc/mdi238
To provide a guideline for the use of antimicrobial prophylaxis for patients in an allogeneic bone marrow transplantation setting.
This was classified as a guideline of evidence-based medicine criteria. The author used a table to rate available evidence-based articles about antimicrobial prophylaxis in allogeneic bone marrow transplant recipients.
Evidence was rated using this table.
Category, Grade Definition
Strength of Recommendation
A Good evidence to support a recommendation for use (strongly recommended)
B Moderate evidence to support a recommendation for use (generally recommended)
C Poor evidence to support a recommendation (optional)
D Moderate evidence to support a recommendation against use (generally not recommended)
E Good evidence to support a recommendation against use (never recommended)
Quality of Evidence
I Evidence from at least one well-executed randomized, controlled trial
II Evidence from at least one well-designed clinical trial without randomization; cohort or
case-controlled analytic studies (preferable from more than one center); multiple time-series
studies; or dramatic results from uncontrolled experiments
III Evidence from opinions of respected authorities based on clinical experience, descriptive
studies, or reports of expert committees.
Al: Fluoroquinolones should be used for antibacterial prophylaxis.
BII: Pneumococcus prophylaxis should be used for any patient with active chronic graft-versus-host disease and for the remainder of the patient's life following splenectomy.
BIII: Patients already receiving Pneumocystis carinii pneumonia (PCP)-prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMZ) should have additional prophylaxis based on the epidemiology for the area and patterns of resistance.
DI: Anti-infectious prophylaxis with intravenous immunoglobulins should be used.
AIII: All patients being considered for allogeneic stem cell transplant should have anti-cytomegalovirus (CMV) IgG-antibody testing. This is recommended to establish the risk for reactivation (de novo infection).
BIII: CMV-negative transplant candidates and patients should not share drinking cups or eating utensils that have been used by others. If a patient who is CMV-negative is in a monogamous relationship, his/her partner is advised to be CMV-serotested. If his/her partner is positive or the patient is not in a monogamous relationship, condom use during sexual contact is recommended.
Al: Transplant recipients who are CMV-seronegative should receive blood products from donors who have also tested negative. When blood banks lack CMV-negative donors, only leukocyte-depleted red cells and thrombocytes should be issued to this group.
DI: CMV prophylaxis should use preparations of human immunoglobulin for CMV-negative matched related donors.
Preventing Disease and Reactivation
BIII: For a CMV-positive recipient, most transplant physicians recommend a CMV-positive donor.
Al: Any patient at risk for CMV disease should be screened for pp65 antigenemia or nucleic acid using real-time polymerase chain reaction (PCR) at least weekly after transplant from days 10 to 100.
Al: Patients should begin pre-emptive therapy following one positive pp65 or two consecutive PCR results. Pre-emptive therapy is advised for two weeks, followed by another two weeks of maintenance therapy.
AI: In a pre-emptive setting, if the patient has resistance to ganciclovir, switching to foscarnet is recommended.
AI: The recommendation for herpes simplex virus (HSV) reactivation in IgG-positive patients is acyclovir. Acyclovir therapy should begin between the start of conditioning therapy and day 1 after the transplant and should continue until day 30 after stem cell transplantation.
Al: The recommendation of drugs for prophylaxis or therapy of CMV are ganciclovir and foscarnet. (Cidofovir has a BII recommendation.)
EI: High-dose acyclovir and valacyclovir should be used to prevent CMV.
El: Human immunoglobulins should be used for prophylaxis or therapy of CMV.
Herpes Simplex Virus
AIII: Serum tests for anti-HSV serostatus are mandatory.
AI: Acyclovir should be used for standard reactivation prophylaxis, beginning between the start of conditioning therapy and day 1 posttransplant and continuing to day 30 following stem cell transplant.
CI: Evidence is lacking for the use of acyclovir prophylaxis increased to 100 days or more.
BIII: If repeated reactivation is present after 30 days of prophylaxis, continued therapy is recommended.
EIII: Acyclovir is not recommended for continued HSV prophylaxis at times when gancyclovir or foscarnet is used for CMV therapy or prophylaxis because gancyclovir and foscarnet are effective against HSV in vitro.
CIII: The effectiveness of valacyclovir and famciclovir in preventing HSV reactivation lacks the support of trials, but they are presumed effective.
AIII: All patients being considered for stem cell transplant should avoid contact with those suspected of active varicella-zoster virus (VZV) infection or reactivation.
BIII: Those living with or in close contact with a transplant patient should be vaccinated before transplant.
AIII: To prevent nosocomial spread, transplant patients with overt VZV disease are to be isolated until all lesions are crusted.
CIII: Long-term acyclovir prophylaxis is not effective for prevention.
AIII: Seronegative transplant candidates and patients with Epstein-Barr virus (EBV) should not share drinking cups or eating utensils that have been used by others. If a patient negative for EBV is in a monogamous relationship, his/her partner is advised to be EBV-serotested. If his/her partner is positive or the patient is not in a monogamous relationship, condom use during sexual contact is recommended.
Community Respiratory Virus
AIII: Exposure prophylaxis is critical in avoiding respiratory syncytial virus, influenza, parainfluenza, and adenovirus.
BII: Those living with or working on units with transplant patients should be vaccinated for influenza.
BIII: Patients should receive a two-week course of amantadine or rimantadine for chemoprophylaxis if vaccination occurred during an influenza outbreak.
CIII: Foods at risk for allowing fungi to colonize in the gastrointestinal (GI) tract should be restricted.
AIII: Hand washing and disinfecting by personnel should be performed to prevent GI-colonizing fungi from reaching patients at risk.
Al: It is recommended to take fluconazole 400 mg/day IV or orally to prevent yeast infections in allogeneic stem cell recipients while they are neutropenic.
BI: One study found itraconazole superior to fluconazole but noted that GI side effects can limit oral use.
EII: Itraconazole is not recommended for yeast prophylaxis because of interactions with metabolism of busulfan.
EI: Itraconazole is not recommended for yeast prophylaxis because of interactions with metabolism of cyclophosphamide.
AII: Stem cell transplant candidates and patients must avoid construction, renovation, or other areas with dust exposure.
AII: Use of air conditioning with high-efficiency particulate absorption filtration or laminar air flow in transplant units reduces mold spore presence in the air and mortality related to fungal invasion.
BIII: Transplant patients should wear appropriate fitting masks when traveling through or to areas off the transplant unit.
BII: No drug demonstrates effectiveness for the primary prophylaxis of aspergillosis following bone marrow transplant.
DII: Itraconazole capsules are limited based on low bioavailability.
AI: For patients with acute leukemia, itraconazole solution reduced the incidence of invasive aspergillosis if plasma levels were greater than 500 ng/mL.
AIII: Secondary prophylaxis with a drug having systemic effectiveness was recommended despite a lack of trial evidence.
Pneumocystis jiroveci (formerly Pneumocystis carinii)
BIII: Stem cell recipients are not to have contact with patients with known PCP.
AII: TMP-SMZ prophylaxis should be used for all allogeneic transplant patients beginning at engraftment until the completion of immunosuppressive therapy or when chronic graft-versus-host disease is resolved.
AII: Dapsone or aerosolized pentacarinate should be used when TMP-SMZ is contraindicated or when the patient does not tolerate it. Higher breakthrough rates are noted with these alternate drugs.
AIII: Allograft recipient candidates should be tested for Toxoplasma gondii antibodies to identify risk for reactivation. Education should include ways to avoid exposure.
CIII: Toxoplasma prophylaxis at the time of acute graft-versus-host disease or secondary prophylaxis following history of toxoplasmosis should be performed.
BIII: Foods with a risk of fungi, bacteria, or other contamination should be eliminated during and following stem cell transplant, and safer alternatives should be used (e.g., pasteurized cheese instead of unpasteurized cheese).
Vaccination After Stem Cell Transplant
AIII: Immunity against specific pathogens should be analyzed one year after allogeneic transplant with reimmunization with inactivated vaccine or toxoids.
The article also states that stem cell transplant recipients are not to receive live-attenuated virus vaccination during the two years after transplant. No rating was provided for this “strictly contraindicated” recommendation.
Specific recommendations with strong evidence, AI and EI, should be included in nursing practice guidelines with recommendations for and against practice, respectively. Other recommendations should not be included until higher evidence from trials can be demonstrated or included in the “Evidence Not Established” category.