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In Vitro Activity of Amphotericin B in Combination with Colistin against Fungi Responsible for Invasive Infections
Patrick Schwarz1,2, Ilya Nikolskiy2,3, Anne-Laure Bidaud4
1Department of Internal Medicine, Respiratory and Critical Care Medicine, University Hospital Marburg, 35033 Marburg, Germany.
Journal of Fungi (Basel, Switzerland)
|February 25, 2022
Summary
The antifungal combination of amphotericin B and colistin showed synergistic effects against most Candida species, but indifferent interactions against Aspergillus and Rhizopus species. This combination holds potential for treating certain fungal infections.
Area of Science:
- Mycology
- Antimicrobial Chemotherapy
- Infectious Diseases
Background:
- Emerging drug-resistant fungal infections pose a significant global health threat.
- Combination antifungal therapy is a promising strategy to overcome resistance and enhance efficacy.
- Amphotericin B and colistin are established antimicrobial agents with distinct mechanisms of action.
Purpose of the Study:
- To evaluate the in vitro synergistic, antagonistic, or indifferent interactions of amphotericin B and colistin against a broad spectrum of fungal pathogens.
- To assess the efficacy of this combination against clinically relevant Candida, Aspergillus, and Rhizopus species.
Main Methods:
- A microdilution checkerboard technique, adhering to European Committee on Antimicrobial Susceptibility Testing (EUCAST) guidelines, was employed.
- Interactions were quantified using the fractional inhibitory concentration index (FICI) based on the Loewe additivity model.
- Response surface analysis, based on the Bliss independence model, was additionally used for Candida species to capture interactions at both MIC and sub-MIC levels.
Main Results:
- The combination demonstrated synergy against 75% of Candida species by FICI and 66% by response surface analysis.
- Synergistic interactions were observed in 73% of Candida auris strains via response surface analysis, contrasting with 33% by FICI, suggesting FICI's insensitivity to weak interactions.
- Interactions against Aspergillus and Rhizopus species were predominantly indifferent, with no significant synergy or antagonism observed.
Conclusions:
- The combination of amphotericin B and colistin exhibits significant synergistic potential against common Candida species, including Candida auris.
- The observed discrepancies in synergy detection highlight the importance of employing multiple analytical models for interaction assessment.
- This combination shows limited efficacy against Aspergillus and Rhizopus species, suggesting its application may be restricted to specific candidal infections.
