Wild-type MIC distributions and epidemiological cutoff values for 5-flucytosine and species as determined by EUCAST broth microdilution.

Objectives: EUCAST has established clinical breakpoints and epidemiological cutoff values (ECOFFs) for spp. However, limited data are available for 5-flucytosine (5-FC). We assessed the susceptibility of 5-FC against a large collection of clinical species using EUCAST methodology and determined the associated ECOFFs.

Methods: A total of 5622 isolates were collected from patients across the Netherlands between 2008 and 2024. 5-FC MICs were determined using the EUCAST microbroth dilution reference method. Furthermore, MICs were extracted from the EUCAST website. The MICs from this study and those extracted were used to determine ECOFFs and local ECOFFs (L-ECOFFs).

Results: 5-FC exhibited potent activity against , and while decreased susceptibility was observed for and The ECOFFs (mg/L) and the percentages of WT isolates for 5-FC were: : 0.5 (97.2%), : 0.5 (96.6%), : 0.5 (99.5%) and : 8 (99.4%). The L-ECOFF (mg/L) and the percentages of WT isolates for 5-FC were: : 0.25 (96.8%), : 0.25 (67.2%), : 0.25 (48.0%), : 0.25 (86.5%), : 0.125 (95.9%) and : 8 (94.2%).

Conclusions: 5-FC remains a valuable drug to manage difficult-to-treat invasive infections. susceptibility cannot be predicted based on species identification for most species, but requires MIC-testing. ECOFFs will help to interpret the MICs to support treatment decisions.