High-Level Carbapenem Resistance in OXA-232-Producing Raoultella ornithinolytica Triggered by Ertapenem Therapy

OXA-232 is an OXA-48-group class D β-lactamase that hydrolyzes expanded-spectrum cephalosporins and carbapenems at low levels. Clinical strains producing OXA-232 are sometimes susceptible to carbapenems, making it difficult to identify them in the clinical microbiology laboratory. We describe the development of carbapenem resistance in sequential clinical isolates of carrying in a hospitalized patient, where the ertapenem MIC increased from 0.5 μg/ml to 512 μg/ml and the meropenem MIC increased from 0.125 μg/ml to 32 μg/ml during the course of ertapenem therapy. Whole-genome sequencing (WGS) analysis identified loss-of-function mutations in and in carbapenem-resistant isolates that were not present in the initial carbapenem-susceptible isolate. Complementation of a carbapenem-resistant isolate with an intact gene resulted in 16- to 32-fold reductions in carbapenem MICs, whereas complementation with intact resulted in a 2-fold reduction in carbapenem MICs. Additionally, expression increased 2.9-fold in a carbapenem-resistant isolate. Rapid development of high-level carbapenem resistance in initially carbapenem-susceptible OXA-232-producing under selective pressure from carbapenem therapy highlights the diagnostic challenges in detecting strains producing this inefficient carbapenemase.