Early Empiric Antifungal Treatment Of Infections In Neutropenic Patients Comparing Fluconazole (Fca) With Amphotericin-B/5-Flucytosine (Abf)

In order to improve outcome in neutropenic patients with hematological malignancies we administered i.v. antifungal agents early as part of an empiric antimicrobial regimen. Additionally, we compared the tolerability and efficacy of fluconazole (FCA) versus amphotericin B and 5-flucytosine (ABF) within a prospective randomized study. Antifungal treatment started on day 4 if fever of >38.5°C did not respond to i.v. antibiotics. In the case of additional pulmonary infiltrates or other evidence of invasive fungal infection, antifungal treatment started upfront together with the antibiotics. If fever or infiltrates persisted after 1 week, FCA was replaced by ABF. A total of 98 patients entered the study, 49 in each arm; all suffered from severe neutropenia with neutrophils <1000/µl. A total of 42 FCA and 41 ABF patients suffered from fever of unknown origin; eight and seven respectively, had pulmonary infiltrates when fever occurred. Response to fever was achieved in 29/39 FCA and 37/49 ABF. This difference was statistically not significant. Fourteen of 20 nonresponders to FCA responded when ABF was given, so an overall response of 81.6% was achieved. In this high-risk population, 20 patients died, six in the FCA and 14 in ABF arm. Among those death six and eight were due to infections, four and five were fungal infections, and one and four patients died form aspergillosis. We conclude that FCA and ABF seem to be equally effective in controlling microbiologically non-documented infections in neutropenic patients with hematological malignancies. Because of its lower toxicity, FCA may be preferred as a first-line empiric antifungal agent and—in the case of non-response-be replaced after 1 week.