Treatment of Invasive Candidal Infections: Systematic Review and Meta-analysis

Abstract

To compare available antifungal treatments for invasive candidiasis, a leading cause of nosocomial bloodstream infections. We performed a systematic review and meta-analysis of randomized controlled trials that compared different antifungal agents for the treatment of candidemia and other forms of invasive candidiasis. Two reviewers independently appraised the quality of trials and extracted data. The primary outcome was all-cause mortality, and secondary outcomes were microbiological failure, treatment failure, and adverse events. Relative risks (RRs) with 95% confidence intervals (CIs) were pooled. Of the 15 included trials, 9 compared fluconazole with other drugs (amphotericin B, itraconazole, or a combination of fluconazole and amphotericin B), 4 compared echinocandins with other drugs (fluconazole, amphotericin B, liposomal amphotericin B), 1 compared micafungin and caspofungin, and 1 compared amphotericin B plus fluconazole and voriconazole. No difference in mortality was observed with fluconazole vs amphotericin B (RR, 0.92; 95% CI, 0.72-1.17); however, the rate of microbiological failure increased in the fluconazole arm (RR, 1.52; 95% CI, 1.12-2.07). Anidulafungin decreased the rate of microbiological failure compared with fluconazole (RR, 0.50; 95% CI, 0.29-0.86) with fewer adverse events. Caspofungin was comparable to amphotericin B in mortality and efficacy, with fewer adverse events requiring discontinuation (RR, 0.11; 95% CI, 0.04-0.36). Micafungin was comparable to liposomal amphotericin B in mortality. All assessed antifungal agents showed similar efficacy, but the rate of microbiological failure increased with fluconazole vs amphotericin B or anidulafungin. Amphotericin B is associated with a higher rate of adverse events than fluconazole and echinocandins.