Investigation of OXA-48 Variants in Enterobacterales Isolates from an OXA-48-Endemic Region

Since their first identification in Türkiye in 2001, OXA-48-like carbapenemases have posed diagnostic challenges due to variant-specific phenotypic and resistance profiles. We investigated the distribution of OXA-48 variants and their association with antimicrobial susceptibility, carbapenem minimum inhibitory concentrations (MICs), phenotypic detection performance, and single- or dual-carbapenemase production. A total of 703 clinical carbapenem-resistant Enterobacterales isolates recovered over 5 years were included. Identification and antimicrobial susceptibility testing were performed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) and an automated system; carbapenem MICs by broth microdilution; carbapenemase genes by multiplex qPCR; and OXA-48 variants by sequence analysis. CNPt-direct and mCIM were performed for OXA-48 variants. OXA-48-like, NDM, and KPC carbapenemases were detected in 52.3%, 11.7%, and 11.5% of isolates, respectively, with co-production observed in 11.7% of OXA-48-like-positive isolates. The most common OXA-48 variants were OXA-48/245 (39.1%), OXA-232 (36.4%), and OXA-181 (17.6%), while OXA-244, OXA-162, and OXA-1200 were less frequent. This study represents the first report of the OXA-1200 variant from Türkiye. OXA-48/245 was the variant most commonly co-produced with other carbapenemases, whereas OXA-244 predominated among CNPt-direct-negative isolates. Susceptibility to meropenem and imipenem among OXA-48-like producers was 31% and 39.1%, respectively, with higher carbapenem MIC₅₀ values observed for OXA-181, OXA-232, and OXA-48/245 compared to OXA-244. In K. pneumoniae, meropenem resistance rates were higher with OXA-48/245, OXA-232, and OXA-181 than with other variants. MIC₅₀ values of carbapenem were higher in dual carbapenemase producers compared to single carbapenemase producers. Our findings show that OXA-48 variants significantly impact resistance profiles, MIC values, and the sensitivity of phenotypic tests and detection of co-produced carbapenemases. Understanding their regional distribution is crucial for targeted prevention strategies.