Wild-type MIC distributions and Epidemiological Cut-off Values for Ibrexafungerp, Manogepix, and Rezafungin against WHO Fungal Priority Pathogens.

Gaps in antifungal susceptibility testing include issues with interpretation of the variability of minimum inhibitory concentrations, which eventually will help guide treatment decisions and monitor the emergence of resistance. This study gathered public data regarding the in vitro activity of three novel antifungal agents, ibrexafungerp, manogepix, and rezafungin, against the fungi listed in the world health organization (WHO) fungal priority pathogens list. A total of 34,736 MIC values were collected from studies using standardised CLSI (25,027) or EUCAST (9,709) methodologies. Epidemiological cut-off values (ECVs/ECOFFs) were established for species with sufficient data (≥100 MIC values) and when distributions met further essential criteria. For pathogens in which data did not fulfil one or more essential criteria, tentative ECVs (T-ECVs/T-ECOFFs) were proposed. The values were determined by a comprehensive analysis that included visual inspection of histograms and the calculation of ECOFFinder-based values (95% and 97.5%), as well as the Mode + 2 and MIC50 + 2 dilutions. The analysis successfully defined ECVs for several key pathogens, including Candida and Aspergillus species. For other WHO-listed pathogens, particularly filamentous and dimorphic fungi, data remained insufficient for robust analysis. The ECVs and T-ECVs derived herein provide crucial reference points to guide future resistance surveillance and inform the foundational epidemiology needed for clinical breakpoint setting.