Efflux System Overexpression and Decreased OprD Contribute to the Carbapenem Resistance Among Extended-Spectrum Beta-Lactamase-ProducingPseudomonas aeruginosaIsolates from a Chinese University Hospital

Abstract

The aim of this study was to investigate, for the first time, the combinations of carbapenem resistance mechanisms in clinical isolates of extended-spectrum beta-lactamase (ESBL)-producing Pseudomonas aeruginosa in a Chinese hospital. Pulsed-field gel electrophoresis revealed the presence of eight clonal types among the 15 ESBL producers. Multilocus sequence typing of two isolates harboured blaIMP-1 identified the clonal strain as ST325. All these genes were found either alone or simultaneously in the strains in the following five different arrangements:<blaOXA-10>; <blaOXA-10, blaIMP-1>; <blaPER-1, blaOXA-10>; <blaPER-1, blaPSE-1>; <blaOXA-10, blaTEM-1>. Regarding mutation-driven resistance, all, but four of the isolates had a relevant decrease of oprD expression. In addition, 73.3% of the isolates overexpressed mexB, 40% mexD, and 33.3% mexY. A specific combination of overexpressed mexB or mexY and alteration in loop L710 of OprD were significantly associated with meropenem resistance. In conclusion, combination of several mutation-driven mechanisms leading to OprD inactivation and overexpression of efflux systems was the main carbapenem resistance mechanism among the ESBL-producing P. aeruginosa isolates, but acquisition of a transferable resistance determinant such as metallo-β-lactamase could be problematic in clinical settings in China.