Comparative effectiveness of amphotericin B, azoles and echinocandins in the treatment of candidemia and invasive candidiasis: A systematic review and network meta-analysis

Background + Objectives The echinocandins, amphotericin B preparations, voriconazole and fluconazole are approved for the treatment of invasive candidiasis, though it remains unclear which agent is most effective. In order to answer this question, we performed a systematic review and network meta-analysis of the randomised controlled trials (RCTs) which evaluated these agents in comparison. Methods Four electronic databases were searched from database inception to 8 October 2020. RCTs comparing triazoles, echinocandins or amphotericin B for the treatment of invasive candidiasis or candidemia were included. Random effect Bayesian network meta-analysis methods were used to compare treatment outcomes. Results Thirteen RCTs met inclusion criteria. Of the 3528 patients included from these trials, 1531 were randomised to receive an echinocandin, 944 to amphotericin B and 1053 to a triazole. For all forms of invasive candidiasis, echinocandins were associated with the highest rate of treatment success when compared to amphotericin B (OR 1.41, 95% CI 1.04-1.92) and the triazoles (OR 1.82, 95% CI 1.35-2.51). Rank probability analysis favoured echinocandins as the most effective choice 98% of the time. Overall survival did not significantly differ between groups. Conclusions Among patients with invasive candidiasis, echinocandins had the best clinical outcomes and should remain the first-line agents in the treatment of invasive candidiasis.