Antifungal combinations in Mucorales: A microbiological perspective

Area of Science:

• Mycology
• Infectious Diseases
• Pharmacology

Background:

• Mucormycosis presents a significant threat to immunocompromised individuals, often leading to severe outcomes.
• Current monotherapies for mucormycosis have limitations, driving interest in combination therapies.

Purpose of the Study:

• To review and analyze existing data on combination therapies for mucormycosis.
• To evaluate in vitro, animal model, and clinical evidence for combination treatments.

Main Methods:

• Systematic review of in vitro studies assessing drug interactions.
• Analysis of in vivo data from animal models of mucormycosis.
• Review of clinical case studies and trials involving combination therapies.

Main Results:

• In vitro studies revealed mostly indifferent interactions, with some synergy noted for echinocandins combined with azoles or amphotericin B; antagonism was absent.
• Animal models, primarily using Rhizopus arrhizus, showed limited synergistic interactions.
• Clinical data indicated efficacy for polyene and caspofungin combinations in specific cases, but adjunctive deferasirox therapy worsened outcomes.

Conclusions:

• Antifungal combination therapy for mucormycosis requires further investigation, particularly with a broader range of Mucorales species and in vitro testing.
• While some combinations show potential, robust clinical evidence is lacking, and certain adjunctive therapies may be detrimental.