Molecular analysis of metallo-beta-lactamase-producing Pseudomonas aeruginosa in Switzerland 2022-2023

Eur J Clin Microbiol Infect Dis. 2024 Mar;43(3):551-557. doi: 10.1007/s10096-024-04752-8. Epub 2024 Jan 18.

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.

Keywords: Pseudomonas aeruginosa; Carbapenems; Epidemiology; Metallo-beta-lactamase.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Carbapenems / pharmacology
  • Humans
  • Microbial Sensitivity Tests
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa*
  • Switzerland / epidemiology
  • beta-Lactamases / genetics

Substances

  • beta-Lactamases
  • Anti-Bacterial Agents
  • Carbapenems