Effect of Prophylactic Fluconazole on the Frequency of Fungal Infections, Amphotericin B Use, and Health Care Costs in Patients Undergoing Intensive Chemotherapy for Hematologic Neoplasias

Abstract

Fungal infections are a major problem in patients with hematologic malignancy. Attempts to reduce their frequency with antifungal agents have not been successful. A double-blind, controlled, single-center trial was conducted with 96 consecutive patients undergoing 154 episodes of chemotherapy. Patients received 400 mg of fluconazole or placebo until bone marrow recovery or initiation of intravenous amphotericin B infusions. End points were amphotericin B use, fungal infection, stable neutrophil count >0.5 X 10 9 /L, toxicity precluding further fluconazole use, and death. By KaplanMeier estimation, the time to initiation of amphotericin B therapy was shorter in 76 patients treated with placebo than in 75 treated with fluconazole (P = .003). Also, fluconazole reduced the number of febrile days by 20% (P = .002) and prevented oropharyngeal candidiasis (1/75 vs. 9/76, P = .018).The frequency of deep mycoses (8/76 vs. 8/75) and outcome were unaffected. Fluconazole did not have a favorable effect on infection-related health care costs and was associated with prolonged severe neutropenia (P = .01).

Candidemia in acute leukemia patients

“…The candidemia rate of 6.3% found in our AL patients is similar to rates published in the literature [1,4,16]. The growing incidence of non-albicans species has recently been stressed and reaches 46% of fungal infections in some studies [19]; this change is probably related to the prophylactic use of triazoles.…”

Network Meta-analysis and Pharmacoeconomic Evaluation of Fluconazole, Itraconazole, Posaconazole, and Voriconazole in Invasive Fungal Infection Prophylaxis

“…We analyzed 19 and 14 studies that reported overall mortality rates at 100 days (12,(20)(21)(22)(23)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38) (Fig. 4c).…”

Primary prophylaxis of invasive fungal infections in patients with hematologic malignancies. Recommendations of the Infectious Diseases Working Party of the German Society for Haematology and Oncology

“…21 Moreover, two more trials comparing fluconazole 400 mg/d versus placebo in non-transplant settings found no significant effect on the incidence rate of proven invasive fungal infections and mortality. 22,23 Doses lower than 400 mg/d failed to show a marked benefit and have not been carried out in a placebo controlled fashion. 17,[24][25][26][27] Since moulds and Candida krusei, harbor intrinsic resistance to fluconazole and only dose dependent activity against Candida glabrata, breakthrough infections with these fungi have occurred.…”