1. Academic Validation
  2. CTX-M-33, a CTX-M-15 derivative conferring reduced susceptibility to carbapenems

CTX-M-33, a CTX-M-15 derivative conferring reduced susceptibility to carbapenems

  • Antimicrob Agents Chemother. 2019 Sep 16;63(12):e01515-19. doi: 10.1128/AAC.01515-19.
Laurent Poirel 1 2 3 José-Manuel Ortiz de la Rosa 4 Anaïs Richard 4 Marta Aires-de-Sousa 5 Patrice Nordmann 4 2 3 6
Affiliations

Affiliations

  • 1 Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg laurent.poirel@unifr.ch.
  • 2 INSERM European Unit (LEA), IAME, Paris, France.
  • 3 Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg, Switzerland.
  • 4 Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg.
  • 5 Escola Superior de Saúde da Cruz Vermelha Portuguesa (ESSCVP), Lisbon, Portugal.
  • 6 University of Lausanne and University hospital Center, Lausanne, Switzerland.
Abstract

CTX-M-type extended-spectrum ß-lactamases (ESBL) are widespread among Enterobacterales worldwide. The most common variant is CTX-M-15 hydrolyzing ceftazidime at high rate, but sparing carbapenems. We identified here CTX-M-33, a point mutant derivative of CTX-M-15 (Asp to Ser substitution at Ambler position 109), exhibiting a low carbapenemase activity. ß-Lactamase CTX-M-33 was identified in a Klebsiella pneumoniae isolate belonging to ST405, lacking the outer membrane protein OmpK36, that was resistant to broad-spectrum cephalosporins and ß-lactam/ß-lactamase inhibitor combinations, and displayed a decreased susceptibility to carbapenems. Comparative hydrolytic activity assays showed that CTX-M-33 hydrolyzed ceftazidime at a lower level than CTX-M-15, but significantly hydrolyzed meropenem. In addition, CTX-M-33 showed higher Mutant Prevention Concentration values and wider mutant selection window in presence of meropenem, in accordance with its observed hydrolytic properties. We identified here the very first CTX-M Enzyme possessing a weak carbapenemase activity, that may correspond to an emerging phenomenon when considering its possibility to evolve from the widespread ESBL CTX-M-15.

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