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Adverse Effects Associated With Currently Commonly Used Antifungal Agents: A Network Meta-Analysis and Systematic

Yan-Li Yang1, Zi-Jian Xiang2, Jing-Hua Yang2

  • 1Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Frontiers in Pharmacology
|November 15, 2021
PubMed

Insights

Echinocandins demonstrate superior tolerability and safety compared to other antifungal agents for invasive fungal infections (IFI). Amphotericin B lipid complex (LAmB) exhibits the most adverse events, while triazoles present specific risks like liver and visual disturbances.

Area of Science:

  • Infectious Diseases
  • Pharmacology
  • Clinical Medicine

Background:

  • Invasive fungal infections (IFI) significantly contribute to morbidity and mortality in immunocompromised and critically ill patients.
  • Long-term antifungal therapy raises concerns regarding drug tolerability and treatment-related toxicity.
  • Understanding comparative safety profiles is crucial for optimizing IFI management.

Purpose of the Study:

  • To systematically compare the safety and tolerability of various antifungal agents used for invasive fungal infections.
  • To identify antifungal drugs with the lowest incidence of adverse events and treatment discontinuation.
  • To inform clinical decision-making by highlighting the risk-benefit profiles of different antifungal treatments.

Main Methods:

  • A comprehensive literature search was conducted across four major electronic databases (Web of Science, Cochrane Library, Embase, PubMed) up to June 30, 2020.
  • Inclusion criteria identified 66 trials involving 18,230 participants.
  • Network meta-analyses were performed on 13 specific adverse events (AEs) categorized by system organ classes and laboratory findings.

Main Results:

  • Echinocandins (anidulafungin, caspofungin, micafungin) showed significantly lower rates of therapy discontinuation due to AEs compared to liposomal amphotericin B (LAmB).
  • Triazole drugs (fluconazole, posaconazole) also demonstrated a lower incidence of AE-related discontinuation versus LAmB.
  • LAmB was associated with the highest number and broadest range of adverse events, indicating the lowest tolerability.

Conclusions:

  • Echinocandin antifungals are the most well-tolerated and safest options for treating invasive fungal infections.
  • Triazole-associated adverse events primarily involve hepatic, neurological (especially visual), gastrointestinal, and cardiac systems.
  • LAmB presents the most significant tolerability challenges and the most extensive spectrum of adverse events among the evaluated antifungal agents.
Keywords:
adverse eventsantineoplastic agentsechinocandinsinvasive fungal infectionsliposomal amphotericin Btriazole

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