Challenging Antimicrobial Susceptibility and Evolution of Resistance (OXA-681) during Treatment of a Long-Term Nosocomial Infection Caused by a Pseudomonas aeruginosa ST175 Clone

Antimicrobial Agents and Chemotherapy
Jorge Arca-SuárezAntonio Oliver

Abstract

Selection of extended-spectrum mutations in narrow-spectrum oxacillinases (e.g., OXA-2 and OXA-10) is an emerging mechanism for development of in vivo resistance to ceftolozane-tazobactam and ceftazidime-avibactam in Pseudomonas aeruginosa Detection of these challenging enzymes therefore seems essential to prevent clinical failure, but the complex phenotypic plasticity exhibited by this species may often lead to their underestimation. The underlying resistance mechanisms of two sequence type 175 (ST175) P. aeruginosa isolates showing multidrug-resistant phenotypes and recovered at early and late stages of a long-term nosocomial infection were evaluated. Whole-genome sequencing (WGS) was used to investigate resistance genomics, whereas molecular and biochemical methods were used for characterization of a novel extended-spectrum OXA-2 variant selected during therapy. The metallo-β-lactamase blaVIM-20 and the narrow-spectrum oxacillinase blaOXA-2 were present in both isolates, although they differed by an inactivating mutation in the mexB subunit, present only in the early isolate, and in a mutation in the blaOXA-2 β-lactamase, present only in the final isolate. The new OXA-2 variant, designated OXA-681, conferred elevated MICs of...Continue Reading

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Sep 7, 2017·Antimicrobial Agents and Chemotherapy·Ester Del Barrio-TofiñoAntonio Oliver
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Sep 7, 2018·The Journal of Antimicrobial Chemotherapy·Gabriel CabotAntonio Oliver

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Citations

Oct 13, 2020·International Journal of Antimicrobial Agents·Ester Del Barrio-TofiñoAntonio Oliver
Dec 10, 2020·International Journal of Molecular Sciences·Juan C Vázquez-UchaAlejandro Beceiro

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