Increasing Trends of Association of 16S rRNA Methylases and Carbapenemases in Enterobacterales Clinical Isolates from Switzerland, 2017-2020

• Published in: Microorganisms (Basel) Vol. 10; no. 3; p. 615
• Main Authors: Fournier, Claudine, Poirel, Laurent, Despont, Sarah, Kessler, Julie, Nordmann, Patrice
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 14.03.2022; MDPI
• Subjects: 16S rRNA methylases; Aminoglycoside antibiotics; Aminoglycosides; Antibiotic resistance; Antibiotics; Antiinfectives and antibacterials; association; Bacteria; Carbapenemase; carbapenemases; Carbapenems; Clinical isolates; co-occurrence; Drug resistance; E coli; Enterobacterales; Enzymes; Genes; Gram-negative bacteria; Incompatibility; Infections; Localization; Multilocus sequence typing; Plasmids; rRNA 16S; Sodium; β Lactamase; β-Lactam antibiotics; France; Switzerland; association; co-occurrence; Enterobacterales; carbapenemases; 16S rRNA methylases
• ISSN: 2076-2607; 2076-2607
• DOI: 10.3390/microorganisms10030615

Aminoglycosides (AGs) in combination with β-lactams play an important role in antimicrobial therapy in severe infections. Pan-resistance to clinically relevant AGs increasingly arises from the production of 16S rRNA methylases (RMTases) that are mostly encoded by plasmids in Gram-negative bacteria. The recent emergence and spread of isolates encoding RMTases is worrisome, considering that they often co-produce extended-spectrum β-lactamases (ESBLs) or carbapenemases. Our study aimed to retrospectively analyze and characterize the association of carbapenem- and aminoglycoside-resistant clinical isolates in Switzerland during a 3.5-year period between January 2017 and June 2020. A total of 103 pan-aminoglycoside- and carbapenem-resistant clinical isolates were recovered at the NARA (Swiss National Reference Center for Emerging Antibiotic Resistance) during the 2017-2020 period. Carbapenemase and RMTase determinants were identified by PCR and sequencing. The characterization of plasmids bearing resistance determinants was performed by a mating-out assay followed by PCR-based replicon typing (PBRT). Clonality of the isolates was investigated by multilocus sequence typing (MLST). Over the 991 collected at the NARA during this period, 103 (10.4%) of them were resistant to both carbapenems and all aminoglycosides. Among these 103 isolates, 35 isolates produced NDM-like carbapenemases, followed by OXA-48-like ( = 23), KPC-like ( = 21), or no carbapenemase ( = 13), OXA-48-like and NDM-like co-production ( = 7), and VIM-like enzymes ( = 4). The RMTases ArmA, RmtB, RmtC, RmtF, RmtG, and RmtB + RmtF were identified among 51.4%, 13.6%, 4.9%, 24.3%, 1%, and 1%, respectively. Plasmid co-localization of the carbapenemase and the RMTase encoding genes was found among ca. 20% of the isolates. A high diversity was identified in terms of the nature of associations between RMTase and carbapenemase-encoding genes, of incompatibility groups of the corresponding plasmids, and of strain genetic backgrounds, highlighting heterogeneous importations rather than clonal dissemination.