Decision making in antifungal monotherapy versus combination therapy

Area of Science:

• Medical Mycology
• Infectious Diseases
• Pharmacology

Background:

• Novel antifungal agents with improved tolerability enhance combination therapy potential for challenging opportunistic mycoses.
• Current combination antifungal therapy, particularly for invasive mould infections, is largely empirical, highlighting a critical need for improved patient outcomes.
• Clinical trials for combination antifungal therapy in opportunistic mycoses are complex, leading to reliance on preclinical studies.

Purpose of the Study:

• To review the current landscape of combination antifungal therapy for opportunistic mycoses.
• To address the challenges in evaluating the efficacy of combination antifungal treatments.
• To provide guidance on the judicious use of combination antifungal therapy in select patient populations.

Main Methods:

• Review of existing literature on combination antifungal therapy for opportunistic mycoses.
• Analysis of in vitro and animal model studies assessing combined antifungal effects.
• Evaluation of the translational relevance of preclinical data to clinical practice.

Main Results:

• Preclinical methods for assessing combined antifungal effects are not standardized.
• Limited evidence directly links in vitro or animal model data to improved patient outcomes in combination antifungal therapy.
• Despite evidence gaps, established principles can inform the use of combination therapy in specific cases.

Conclusions:

• Combination antifungal therapy holds promise but lacks robust clinical validation for many opportunistic mycoses.
• Standardization of preclinical testing and improved clinical trial design are crucial for advancing combination antifungal strategies.
• Clinical application of combination antifungal therapy should be guided by careful patient selection and existing principles in the absence of definitive evidence.