Wild-type minimum effective concentration distributions and epidemiologic cutoff values for caspofungin and...

Area of Science:

• Medical Mycology
• Antimicrobial Resistance
• Clinical Microbiology

Background:

• Antifungal susceptibility testing for Aspergillus species against caspofungin is standardized by the Clinical and Laboratory Standards Institute (CLSI).
• Breakthrough Aspergillus infections have been documented, with minimum effective concentrations (MEC) for caspofungin varying significantly (0.25 to 8 microg/mL).

Purpose of the Study:

• To determine the wild-type (WT) minimum effective concentration (MEC) distributions for caspofungin across various Aspergillus species.
• To establish epidemiologic cutoff values (ECVs) for caspofungin susceptibility testing in Aspergillus isolates.
• To provide a basis for antifungal resistance surveillance and the development of clinical breakpoints.

Main Methods:

• Tested 1590 clinical isolates of Aspergillus spp. (including A. flavus, A. fumigatus, A. niger, A. terreus, and A. versicolor).
• Utilized the CLSI broth microdilution method for antifungal susceptibility testing against caspofungin.
• Defined epidemiologic cutoff values (ECVs) to encompass wild-type (WT) MEC distributions.

Main Results:

• ECVs of ≤0.06 microg/mL encompassed WT MEC distributions for A. flavus (99.5%), A. fumigatus (98.7%), A. niger (100%), and A. terreus (97.2%).
• An ECV of ≤0.12 microg/mL encompassed the WT distribution for A. versicolor (96.7%).
• Twenty strains exhibited MECs outside the established ECVs, indicating potential resistance or reduced susceptibility.

Conclusions:

• Established WT MEC distributions and ECVs for caspofungin against major Aspergillus species are crucial for resistance surveillance.
• These findings represent a significant step toward developing clinical breakpoints for caspofungin in Aspergillus infections.
• The data will aid in interpreting caspofungin susceptibility test results and managing invasive aspergillosis.