Molecular analysis of metallo-beta-lactamase-producing Pseudomonas aeruginosa in Switzerland 2022–2023
Authors: Findlay Jacqueline , Raro Otavio Hallal Ferreira , Poirel Laurent , Nordmann Patrice ,   NARA Network, Lienhard R. , Vonallmen L. , Schilt C. , Scherler A. , Lucke K. , Jutzi M. , Reichmuth M. , Schibli U. , Fricker C. , Pranghofer S. , Greub G. , Blanc D. , Vitale A. , Lemaire B. , Fatoux M. , Tritten M. , Rumebe L. , Liassine N. , Jost G. , Wohlwend N. , Schultze D. , Burren K. , Westers A. , Imperiali M. , Pozzi L. , Balzari D. , Vaninetti G. , Cirillo C. , Gaia V. , Pianezzi E. , Lucchini G. Martinetti , Menozzi F. Baggi , Jayol A. , Guyon C. , Hyden D. , Maitrejean M. , Deggi-Messmer V. , Bandeira D. , Fournier C. , Pfister S. , Nusbaumer C. , Monnerat L. Bertaiola , Schrenzel J. , Renzi G. , Cherkaoui A. , Andrey D. , Emonet S. , Eyer M. , Maret R. , Belo A. , Mabillard D. , Moraz M. , Herzog K. , Gisler V. , Hitz E. , Oberle M. , Castelberg C. , Fankhauser H. , Graf S. , Dubey N. , Guler C. , Schoenenberger M. , Karrer U. , Piran F. , Andreutti C. , Dessauges M. , Schmid T. , Suterbuser B. , Mitrovic I. , Gruner E. , Bruderer V. , Staehli P. , Schnell B. , Marti C. O. , Steffen I. , Imhof A. , Preiswerk B. , Dilorenzo V. , Payen C. , Boschung D. , Comte L. , Schacher M. , Brandenberger M. , Zowa C. , Zehnder C. , Mathis B. , Basilico L. , Togni G. , Minkova P. , Born Y. , Kuegler M. , Povolo V. , Droz S. , Elzi M. , Casanova C. , Goldenberger D. , Keller P. , Lang C. , Blaich A. , Schmid S. , Ivan B. , Egli A. , Mancini S. , Dubois O. , Narr K. , Schoch S. , Ellenberger S. , Seiffert S. 
Published: January 2024

Abstract
Objectives
The occurrence of metallo-beta-lactamase-producing Pseudomonas aeruginosa (MBL-PA) isolates is increasing globally, including in Switzerland. The aim of this study was to characterise, phenotypically and genotypically, the MBL-PA isolates submitted to the Swiss National Reference Center for Emerging Antibiotic Resistance (NARA) reference laboratory over a 12-month period from July 2022 to July 2023.

Methods
Thirty-nine non-duplicate MBL-PA Isolates were submitted to NARA over the study period from across Switzerland. Susceptibility was determined by broth microdilution according to EUCAST methodology. Whole-genome sequencing was performed on 34 isolates. Sequence types (STs) and resistance genes were ascertained using the Centre for Genomic Epidemiology platform. MBL genes, blaNDM-1, blaIMP-1, and blaVIM-2, were cloned into vector pUCP24 and transformed into P. aeruginosa PA14.

Results
The most prevalent MBL types identified in this study were VIM (21/39; 53.8%) followed by NDM (11/39; 28.2%), IMP (6/39; 15.4%), and a single isolate produced both VIM and NDM enzymes. WGS identified 13 different STs types among the 39 isolates. They all exhibited resistance to cephalosporins, carbapenems, and the beta-lactam-beta-lactamase inhibitor combinations, ceftolozane-tazobactam, ceftazidime-avibactam, imipenem-relebactam, and meropenem-vaborbactam, and 8 isolates were cefiderocol (FDC) resistant. Recombinant P. aeruginosa strains producing blaNDM-1, blaIMP-1, and blaVIM-2 exhibited FDC MICs of 16, 8, and 1 mg/L, respectively.

Conclusions
This study showed that the MBL-PA in Switzerland could be attributed to the wide dissemination of high-risk clones that accounted for most isolates in this study. Although FDC resistance was only found in 8 isolates, MBL carriage was shown to be a major contributor to this phenotype.