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

Poirel, Laurent; Ortiz de la Rosa, José Manuel; Richard, Anaïs; Aires-de-Sousa, Marta; Nordmann, Patrice

doi:10.1128/AAC.01515-19

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Journal article

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

Poirel, Laurent Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland - INSERM European Unit, IAME, Paris, France
Ortiz de la Rosa, José Manuel Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland
Richard, Anaïs Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland
Aires-de-Sousa, Marta Escola Superior de Saúde da Cruz Vermelha Portuguesa, Lisbon, Portugal
Nordmann, Patrice Emerging Antibiotic Resistance Unit, Medical and Molecular Microbiology, Department of Medicine, University of Fribourg, Fribourg, Switzerland - INSERM European Unit, IAME, Paris, France - Swiss National Reference Center for Emerging Antibiotic Resistance, Fribourg, Switzerland

01.12.2019

Published in:

Antimicrobial Agents and Chemotherapy. - 2019, vol. 63, no. 12, p. 10.1128/aac.01515-19

English CTX-M-type extended-spectrum β-lactamases (ESBLs) are widespread among Enterobacterales strains worldwide. The most common variant is CTX-M-15, which hydrolyzes ceftazidime at a high rate but spares carbapenems. Here, we identified CTX-M-33, a point mutation derivative of CTX-M-15 (Asp to Ser substitution at Ambler position 109) that exhibited low carbapenemase activity. β-Lactamase CTX-M-33 was identified in a Klebsiella pneumoniae isolate, belonging to sequence type 405 and lacking the outer membrane protein OmpK36, that was resistant to broad-spectrum cephalosporins and β-lactam/β-lactamase inhibitor combinations and displayed 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 a wider mutant selection window in the presence of meropenem, in accordance with its observed hydrolytic properties. Here, we identified the very first CTX-M enzyme possessing weak carbapenemase activity, which may correspond to an emerging phenomenon, considering its possible evolution from the widespread ESBL CTX-M-15.

Faculty

Faculté des sciences et de médecine

Department

Médecine 3ème année

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