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Broth Microdilution In Vitro Screening: An Easy and Fast Method to Detect New Antifungal Compounds
Published on: February 14, 2018
Effects of serum on in vitro susceptibility testing of echinocandins
Zekaver Odabasi1, Victor Paetznick, John H Rex
1Marmara University, Tophanelioglu caddesi, No:13, 34662 Altunizade, Istanbul, Turkey. zekaver@marmara.edu.tr
Abstract:
The effects of protein binding on the activities of caspofungin, anidulafungin, and micafungin were evaluated against Candida and Aspergillus species. Adding human serum sharply increased the MICs of micafungin and anidulafungin and modestly affected the MIC of caspofungin. The increase in MICs does not appear consistent with the rate of protein binding for the three compounds.
Insights
Protein binding significantly impacts echinocandin antifungal drugs. Human serum increased minimum inhibitory concentrations (MICs) for micafungin and anidulafungin more than caspofungin, despite similar protein binding rates.
Area of Science:
- Pharmacology
- Mycology
- Biochemistry
Background:
- Echinocandin antifungals like caspofungin, anidulafungin, and micafungin are crucial for treating invasive fungal infections.
- Protein binding can influence the efficacy and pharmacokinetics of antimicrobial agents.
- Understanding how protein binding affects echinocandin activity is vital for optimizing treatment strategies.
Purpose of the Study:
- To investigate the impact of protein binding on the in vitro activity of three echinocandin antifungals: caspofungin, anidulafungin, and micafungin.
- To compare the activity of these drugs against common fungal pathogens, Candida and Aspergillus species, in the presence of human serum.
Main Methods:
- Minimum Inhibitory Concentrations (MICs) were determined for caspofungin, anidulafungin, and micafungin.
- Experiments were conducted using fungal isolates of Candida and Aspergillus species.
- The effect of adding human serum (representing protein binding) on drug activity was assessed by comparing MICs in serum-supplemented media versus standard media.
Main Results:
- Human serum significantly increased the MICs of anidulafungin and micafungin against the tested fungal species.
- Caspofungin's MICs were only modestly affected by the addition of human serum.
- The observed increases in MICs did not correlate directly with the known protein binding rates of the three echinocandins.
Conclusions:
- Protein binding, as simulated by human serum, differentially affects the in vitro activity of echinocandin antifungals.
- The relationship between protein binding and echinocandin efficacy is complex and not solely dependent on binding extent.
- Further research is needed to elucidate the precise mechanisms underlying these observed differences in antifungal activity.
