A Meta-analysis of Fluconazole versus Amphotericin B for Treatment of Invasive Candida Infections

• Objective: To compare the efficacy of amphotericin B and fluconazole in the eradication of invasive Candida infections. • Design: Meta-analysis. • Data sources: Published and unpublished randomized controlled trials comparing amphotericin B to fluconazole in the treatment of invasive Candida infections were identified by searches of MEDLINE, the Cochrane Clinical Trials Registry, EMBASE, and the Medical Editors’ Trial Amnesty. The bibliographies of all identified articles and relevant review articles also were examined. • Study selection: For inclusion in the meta-analysis, articles had to meet the following criteria: (1) random allocation of patients, (2) objective inclusion criteria for documented Candida infections, and (3) subjectlevel data collection regarding mortality, microbiological failure, clinical success, and adverse events. • Outcome measures: Mortality, microbiological failure, clinical success, and adverse event rates. • Results: 4 trials with 457 subjects were selected for inclusion in the final analysis. There were no statistically significant differences between the 2 therapies. The relative risk (RR) of death was 0.99 (95% confidence interval [CI], 0.75 to 1.29) when fluconazole subjects were compared with amphotericin B subjects. In the fluconazole-treated group, there was a trend toward microbiological failure (RR = 1.34 [95% CI, 0.77 to 2.34]) and clinical failure (RR = 1.18 [95% CI, 0.90 to 1.52]). In the fluconazole-treated groups, there were also trends toward clinical failure among immunocompetent patients (RR = 1.31 [95% CI, 0.96 to 1.67]) and among those who did not receive flucytosine (RR = 1.19 [95% CI, 0.90 to 1.57]). • Conclusions: While there were no statistically significant differences in death, clinical failure, or microbiological failure between the 2 agents, the RRs for clinical failure and microbiological failure favored amphotericin B for the treatment of invasive Candida infections. Over the past 20 years, the number of invasive infections caused by Candida species has increased in frequency due to advances in the care and prolonged survival of patients with malignancy and end-stage organ diseases [1–3]. Until recently, amphotericin B was the only effective therapy for invasive fungal infections. However, a high incidence of renal toxicity and other side effects associated with this agent have limited its use and led to the development of the better-tolerated azole antifungal drugs, such as fluconazole. Since the late 1980s, there have been a number of randomized controlled trials comparing amphotericin B with fluconazole for the treatment of invasive Candida infections. Although these individual studies found no statistically significant differences in cure or survival frequencies between the 2 treatment groups, the studies were relatively small and therefore may have lacked sufficient power to detect significant differences. Furthermore, other factors such as underlying immunosuppression and catheter exchange practices might affect outcome without being apparent in studies with small sample size and heterogeneous patient populations. We conducted this meta-analysis to derive a more precise comparison of the 2 treatment groups.