Prophylactic action of oral fluconazole against fungal infection in neutropenic patients. A meta-analysis of 16 randomized, controlled trials.
BACKGROUND
Fluconazole is used widely for fungal prophylaxis. Although studies with bone marrow transplantation (BMT) recipients clearly showed the usefulness of oral fluconazole, results of the studies in neutropenic patients other than BMT recipients have been inconsistent. Therefore, the authors performed a meta-analysis to evaluate the efficacy of fluconazole prophylaxis during chemotherapy-induced neutropenia.


METHODS
The authors identified reports that were not restricted to those in English and not restricted to published trials through MEDLINE, CANCERLIT, or the data base of the Pfizer company. The authors included prospective, randomized studies comparing oral fluconazole with placebo, no treatment, or oral polyenes as prophylaxis for fungal infections in neutropenic patients. Two independent authors extracted data from 16 trials with 3734 patients enrolled. The outcome measures were the development of fungal-related death, systemic and superficial fungal infections, the use of empiric intravenous amphotericin-B, and infections or colonization with fluconazole-resistant fungi. The summarized odds ratios (ORs) were calculated using the Mantel-Haenszel method and the DerSimonian-Laird method.


RESULTS
Prophylactic fluconazole was not effective in reducing fungal-related death or in reducing proven, systemic fungal infections in non-BMT patients (OR, 0.91; 95% confidence interval [CI], 0.30-2.82 and OR, 0.85; 95% CI, 0.47-1.55, respectively). However, fluconazole was very effective in reducing superficial fungal infections (OR, 0.44; 95% CI, 0.24-0.80), even when it was given in lower doses (50-200 mg per day). There was no increase in proven, systemic infection of fluconazole-resistant fungi, although colonization of those fungi increased. When the results were combined in studies in which the incidence of systemic fungal infections was > 15%, fluconazole was effective in reducing such infections (OR, 0.23; 95% CI, 0.15-0.36).


CONCLUSIONS
The current analyses failed to find an effect of fluconazole on both fatal fungal infection and systemic fungal infection in non-BMT patients. Further studies on severely neutropenic patients are warranted because prophylactic fluconazole seemed to be effective when the incidence of systemic fungal infection was expected to be > 15%.
Kanda
Y
Y
Department of Hematology, International Medical Center of Japan, Tokyo, Japan. ycanda-tky@umin.ac.jp
Yamamoto
R
R
Chizuka
A
A
Hamaki
T
T
Suguro
M
M
Arai
C
C
Matsuyama
T
T
Takezako
N
N
Miwa
A
A
Kern
W
W
Kami
M
M
Akiyama
H
H
Hirai
H
H
Togawa
A
A
D000284:Administration, Oral; D000935:Antifungal Agents / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects; D015725:Fluconazole / Q000627:therapeutic use*; D006801:Humans; D009181:Mycoses / Q000188:drug therapy* / Q000209:etiology; D009369:Neoplasms / Q000188:drug therapy; D009503:Neutropenia / Q000139:chemically induced* / Q000150:complications* / Q000382:microbiology; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
D000935:Antifungal Agents; D000970:Antineoplastic Agents; D015725:Fluconazole