Network meta-analysis of triazole, polyene, and echinocandin antifungal agents in invasive fungal infection prophylaxis in patients with hematological malignancies

BMC Cancer. 2021 Apr 14;21(1):404. doi: 10.1186/s12885-021-07973-8.

Abstract

Background and aim: Triazole, polyene, and echinocandin antifungal agents are extensively used to treat invasive fungal infections (IFIs); however, the optimal prophylaxis option is not clear. This study aimed to determine the optimal agent against IFIs for patients with hematological malignancies.

Methods: Randomized controlled trials (RCTs) comparing the effectiveness of triazole, polyene, and echinocandin antifungal agents with each other or placebo for IFIs in patients with hematological malignancies were searched. This Bayesian network meta-analysis was performed for all agents.

Results: The network meta-analyses showed that all triazoles, amphotericin B, and caspofungin, but not micafungin, reduced IFIs. Posaconazole was superior to fluconazole [odds ratio (OR), 0.30; 95% credible interval (CrI), 0.12-0.60], itraconazole (OR, 0.40; 95% CrI, 0.15-0.85), and amphotericin B (OR, 4.97; 95% CrI, 1.73-11.35). It also reduced all-cause mortality compared with fluconazole (OR, 0.35; 95% CrI, 0.08-0.96) and itraconazole (OR, 0.33; 95% CrI, 0.07-0.94), and reduced the risk of adverse events compared with fluconazole (OR, 0.02; 95% CrI, 0.00-0.03), itraconazole (OR, 0.01; 95% CrI, 0.00-0.02), posaconazole (OR, 0.02; 95% CrI, 0.00-0.03), voriconazole (OR, 0.005; 95% CrI, 0.00 to 0.01), amphotericin B (OR, 0.004; 95% CrI, 0.00-0.01), and caspofungin (OR, 0.05; 95% CrI, 0.00-0.42) despite no significant difference in the need for empirical treatment and the proportion of successful treatment.

Conclusions: Posaconazole might be an optimal prophylaxis agent because it reduced IFIs, all-cause mortality, and adverse events, despite no difference in the need for empirical treatment and the proportion of successful treatment.

Keywords: Echinocandin; Hematological malignancies; Invasive fungal infections; Network meta-analysis; Polyene; Prophylaxis; Triazole.

Publication types

  • Meta-Analysis

MeSH terms

  • Antifungal Agents / therapeutic use*
  • Echinocandins / administration & dosage
  • Echinocandins / therapeutic use*
  • Hematologic Neoplasms / complications*
  • Humans
  • Invasive Fungal Infections / etiology*
  • Invasive Fungal Infections / prevention & control*
  • Network Meta-Analysis
  • Polyenes / administration & dosage
  • Polyenes / therapeutic use*
  • Pre-Exposure Prophylaxis
  • Publication Bias
  • Treatment Outcome
  • Triazoles / administration & dosage
  • Triazoles / therapeutic use*

Substances

  • Antifungal Agents
  • Echinocandins
  • Polyenes
  • Triazoles