Genetic features leading to reduced susceptibility to aztreonam-avibactam among metallo-β-lactamase-producing escherichia coli isolates

Sadek, Mustafa; Juhas, Mario; Poirel, Laurent; Nordmann, Patrice

doi:10.1128/AAC.01659-20

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Genetic features leading to reduced susceptibility to aztreonam-avibactam among metallo-β-lactamase-producing escherichia coli isolates

Sadek, Mustafa Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
Juhas, Mario Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland
Poirel, Laurent Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland - INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland
Nordmann, Patrice Medical and Molecular Microbiology, Faculty of Science and Medicine, University of Fribourg, Fribourg, Switzerland - Swiss National Reference Center for Emerging Antibiotic Resistance (NARA), University of Fribourg, Fribourg, Switzerland - INSERM European Unit (IAME, France), University of Fribourg, Fribourg, Switzerland

17.11.2020

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Antimicrobial Agents and Chemotherapy. - 2020, vol. 64, no. 12, p. 10.1128/aac.01659-20

English Metallo-β-lactamase (MBL)-producing Escherichia coli isolates resistant to the newly developed β-lactam/β-lactamase inhibitor drug combination aztreonam-avibactam (ATM-AVI) have been reported. Here, we analyzed a series of 118 clinical MBL- producing E. coli isolates of various geographical origins for susceptibility to ATM-AVI. The nature of the PBP3 protein sequence and the occurrence of blaCMY genes for susceptibility to ATM-AVI were investigated. We showed here that elevated MICs of ATM-AVI among MBL-producing E. coli isolates resulted from a combination of different features, including modification of PBP3 protein sequence through specific amino acid insertions and production of CMY-type enzymes, particularly, CMY-42. We showed here that those insertions identified in the PBP3 sequence are not considered the unique basis of resistance to ATM-AVI, but they significantly contribute to it.

Faculty

Faculté des sciences et de médecine

Department

Médecine 3ème année

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