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B. Antifungal Prophylaxis for BMT and Hematologic Malignancies
For allogenic BMT patients, fluconazole prophylaxis has been shown to reduce
the incidence of deep Candida infections.40-42
Itraconazole may be more effective than fluconazole for prevention of invasive
fungal infections but is associated with more frequent GI side effects.43
For patients with hematologic malignancies or solid tumors, no study has shown
a clear benefit of antifungal prophylaxis. High-risk patients with prolonged
neutropenia, however, can be individually considered for this strategy.44
Micafungin has been approved for prophylaxis for stem cell transplant recipients,
but the benefit of prophylaxis with this or other echinocandin must be weighed
against the potential loss of this class of drug for therapeutic purposes. 45
Posaconazole has been approved for prophylaxis for patients with hematologic
malignancies. While preliminary data is encouraging, difficulties with drug
absorption and drug interactions may not make this a suitable prophylaxis
alternative for all patients. Voriconazole should not be automatically substituted
for patients having difficulty with posaconazole.46,47
Patients with hematologic malignancies with significant GVHD >Grade 3 may be
considered candidates for prophylaxis with posaconazole, or occasionally
voriconazole, although evidence based medicine for the later is lacking.48,49
C. Empiric Antifungal Therapy for the Management of Patients with Febrile Neutropenia
In patients with granulocytopenia (<500/mcL) who have had persistent fever for
more than 3-5 days despite empiric antibiotic therapy (cefepime or
piperacillin/tazobactam, with or without tobramycin or ciprofloxacin), the addition
of an antifungal drug to the empiric regimen is desirable and can reduce mortality
from occult deep fungal infection.29 These patients should ideally be screened for
invasive fungal infections through serological and radiographic means.49
Patients may be stratified by their risk of invasive fungal infections as noted
Low risk = not high risk
High risk = febrile patient with one or more of the following:
• Any patient with greater than 21 days of persistent neutropenia after
cytotoxic chemotherapy
• Stem cell transplantation with neutropenia of greater than 5 days
• Patients with relapsed leukemia undergoing reinduction therapy with
neutropenia/fever greater than 5 days
• Stem cell transplant with GVHD >Grade 3 with or without
• Any patient with greater than 7 days of neutropenia, unresponsive to 7
days of azole empiric therapy, with high suspicion of filamentous fungal
Conventional IV amphotericin B (at a dose of 0.5 mg/kg) and lipid-based
amphotericin products (at a dose of 3-5 mg/kg) are both effective.30,31 However,
in patients who have not been receiving fluconazole prophylactically, fluconazole
or itraconazole appear to give comparable results32,33 and voriconazole may be
considered for high-risk patients.