Eleven RCTs (n=965) were included in the review. Overall trial quality was considered to be moderate; individual quality assessment results were not reported.
For global clinical response, a statistically significant pooled effect was found for azoles versus amphotericin B (RR 0.87, 95% CI 0.78 to 0.96, I2=43%; seven trials). Similar effect estimates were reported when fluconazole (five trials), itraconazole (one trial) and voriconazole (one trial) were compared with amphotericin B; only the first of these analyses was statistically significant. Results for anidulafungin compared with fluconazole were also statistically significant (RR 1.26 95% CI 1.06 to 1.51; one trial).
For all-cause mortality, there was no statistically significant effect in the comparison of azoles versus amphotericin B. Similar results were reported for fluconazole (five trials), itraconazole (one trial) and voriconazole (one trial). There were no statistically significant effects in any of the analyses of micafungin versus caspofungin and anidulafungin versus fluconazole.
There were no statistically significant associations for deaths attributable to fungal infection.
Azoles were found to be favourable to amphotericin B in terms of a lower incidence of serious adverse events (RR 0.67, 95% CI 0.55 to 0.81; two trials). Echinocandins were similarly favourable to amphotericin B (RR 0.49, 95% CI 0.37 to 0.66; two trials). Micafungin and caspofungin had similar safety profiles. Azoles were favourable to amphotericin B on nephrotoxicity (RR 0.22, 95% CI 0.15 to 0.32; I2=74%), as were echinocandins (RR 0.31, 95% CI 0.17 to 0.57). The only statistically significant result for hepatic enzyme elevations was in favour of anidulafungin over fluconazole (RR 0.21, 95% CI 0.05 to 0.83).
Mixed-treatment comparison analysis showed that within-class effects were similar across all drug interventions. Absolute response rates ranged from 63% (fluconazole) to 77.49% (anidulafungin). Absolute treatment efficacy in terms of mortality ranged from 20.75% (anidulafungin) to 39.99% (amphotericin B liposomal).
Sensitivity analysis on the dose of amphotericin B did not alter the main results.