High-Level Carbapenem Resistance Among OXA-48-Producing with Functional OmpK36 Alterations: Maintenance of Ceftazidime/Avibactam Susceptibility

The aim of this work was to analyze outer membrane porin-encoding genes ( and ) in a collection of OXA-48 producing , to assess the effect of porin alterations on the susceptibility to ceftazidime/avibactam, and to describe a screening methodology for phenotypic detection of OXA-48-producing with disrupted porins. Antimicrobial susceptibility was tested by Microscan and Etest. The genomes of 81 OXA-48-producing were sequenced. MLST, detection of antimicrobial resistance genes, and analysis of and were performed . Tridimensional structures of the OmpK36 variants were assessed. Receiver operating characteristics curves were built to visualize the performance ability of a disk diffusion assay using carbapenems and cefoxitin to detect OmpK36 functional alterations. A wide variety of OmpK36 alterations were detected in 17 OXA-48-producing isolates. All displayed a high-level meropenem resistance (MIC ≥ 8 mg/L), and some belonged to high-risk clones, such as ST15 and ST147. Alterations in were also observed, but they did not correlate with high-level meropenem resistance. All isolates were susceptible to ceftazidime/avibactam and porin alterations did not affect the MICs of the latter combination. Cefoxitin together with ertapenem/meropenem low inhibition zone diameters (equal or lower than 16 mm) could strongly suggest alterations affecting OmpK36 in OXA-48-producing . OXA-48-producing with porin disruptions are a cause of concern; ceftazidime/avibactam showed good activity against them, so this combination could be positioned as the choice therapy to combat the infections caused by this difficult-to-treat isolates.