Fifteen RCTs (n=3,265) were included.
Seven studies had adequate generation of allocation. Nine studies had adequate allocation concealment. Eight studies had unclear generation of allocation. Six studies had unclear allocation concealment. Six studies had no blinding. One study had blinding (unspecified). Eight studies had double blinding.
Fluconazole versus other fungal agent
There was no evidence of a significant difference between groups in all-cause mortality (seven trials) or treatment failure (eight trials), but there were significantly higher microbiological failure rates with fluconazole compared to amphotericin B (six trials, RR 1.52, 95% CI 1.12, 2.07) and combined amphotericin B plus fluconazole (one trial, RR 2.69, 95% CI 1.17, 6.18).
When subgroup analysis was undertaken, there was no evidence of a significant difference in any of the efficacy outcomes assessed, except that patients with candidemia taking fluconazole had significantly higher rates of treatment failure (two trials) (RR 1.42, 95% CI 0.96, 2.09) than those taking amphotericin B.
Echinocandins versus any other fungal agent
There was no evidence of a significant difference between groups in all-cause mortality for any comparison (four trials). Treatment failure and microbiological failure decreased significantly with anidulafungin versus fluconazole (one trial) (treatment failure RR 0.61, 95% CI 0.42, 0.89 and microbiological failure RR 0.5, 95% CI 0.29, 0.86).
There was no evidence of a significant difference in treatment and microbiological failure between caspofungin versus amphotericin B or micafungin versus liposomal amphotericin B (one or two trials). Subgroup analysis confirmed a lower microbiological failure rate for patients with Candida albicans who took anidulafungin versus fluconazole (one trial), but there was no evidence of significant differences in any of the other subgroup comparisons.
There was no evidence of a significant difference in the outcomes between micafungin versus caspofungin or amphotericin B plus fluconazole versus voriconazole (one trial in the comparisons).
There was no evidence of a difference in the rates of adverse events requiring discontinuation between fluconazole versus other agents (four trials), but fluconazole caused less nephrotoxicity than amphotericin B or combined amphotericin B plus fluconazole (five trials) (RR 0.11, 95% CI 0.03, 0.48; RR 0.12, 95% CI 0.04, 0.39).
All echinocandins had significantly lower rates of adverse events requiring discontinuation when compared with other agents (anidulafungin versus fluconazole RR 0.52, 95% CI 0.29, 0.92, one trial; caspofungin versus amphotericin B: RR 0.11, 95% CI 0.04, 0.36, one trial; micafungin versus liposomal amphotericin B: RR 0.45, 95% CI 0.26, 0.80, two trials).
No evidence of differences in adverse events requiring discontinuation was found when micafungin was compared with caspofungin (one trial).
Adverse events requiring discontinuation were significantly lower (RR 0.47, 95% CI 0.23, 0.93, one trial) and nephrotoxicity was significantly higher (RR 2.64, 95% CI 1.57, 4.44, one trial) for combined amphotericin B plus fluconazole when compared with voriconazole.