Difficult-to-treat (DTR) Pseudomonas aeruginosa harboring Verona-Integron metallo-β-lactamase (blaVIM): infection management and molecular analysis

Antimicrob Agents Chemother. 2024 May 2;68(5):e0147423. doi: 10.1128/aac.01474-23. Epub 2024 Apr 11.


Pseudomonas aeruginosa harboring Verona Integron-encoded metallo-β-lactamase enzymes (VIM-CRPA) have been associated with infection outbreaks in several parts of the world. In the US, however, VIM-CRPA remain rare. Starting in December 2018, we identified a cluster of cases in our institution. Herein, we present our epidemiological investigation and strategies to control/manage these challenging infections. This study was conducted in a large academic healthcare system in Miami, FL, between December 2018 and January 2022. Patients were prospectively identified via rapid molecular diagnostics when cultures revealed carbapenem-resistant P. aeruginosa. Alerts were received in real time by the antimicrobial stewardship program and infection prevention teams. Upon alert recognition, a series of interventions were performed as a coordinated effort. A retrospective chart review was conducted to collect patient demographics, antimicrobial therapy, and clinical outcomes. Thirty-nine VIM-CRPA isolates led to infection in 21 patients. The majority were male (76.2%); the median age was 52 years. The majority were mechanically ventilated (n = 15/21; 71.4%); 47.6% (n = 10/21) received renal replacement therapy at the time of index culture. Respiratory (n = 20/39; 51.3%) or bloodstream (n = 13/39; 33.3%) were the most common sources. Most infections (n = 23/37; 62.2%) were treated with an aztreonam-avibactam regimen. Six patients (28.6%) expired within 30 days of index VIM-CRPA infection. Fourteen isolates were selected for whole genome sequencing. Most of them belonged to ST111 (12/14), and they all carried blaVIM-2 chromosomally. This report describes the clinical experience treating serious VIM-CRPA infections with either aztreonam-ceftazidime/avibactam or cefiderocol in combination with other agents. The importance of implementing infection prevention strategies to curb VIM-CRPA outbreaks is also demonstrated.

Keywords: Pseudomonas aeruginosa; Verona Integron metallo-beta-lactamase; antimicrobial stewardship; carbapenemase; infection prevention.

MeSH terms

  • Adult
  • Anti-Bacterial Agents* / pharmacology
  • Anti-Bacterial Agents* / therapeutic use
  • Antimicrobial Stewardship
  • Azabicyclo Compounds / therapeutic use
  • Aztreonam / pharmacology
  • Aztreonam / therapeutic use
  • Carbapenems / pharmacology
  • Carbapenems / therapeutic use
  • Ceftazidime / pharmacology
  • Ceftazidime / therapeutic use
  • Drug Combinations
  • Drug Resistance, Multiple, Bacterial / genetics
  • Female
  • Humans
  • Integrons / genetics
  • Male
  • Microbial Sensitivity Tests*
  • Middle Aged
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas Infections* / microbiology
  • Pseudomonas aeruginosa* / drug effects
  • Pseudomonas aeruginosa* / genetics
  • Retrospective Studies
  • beta-Lactamases* / genetics


  • Anti-Bacterial Agents
  • avibactam, ceftazidime drug combination
  • Azabicyclo Compounds
  • Aztreonam
  • beta-Lactamases
  • Carbapenems
  • Ceftazidime
  • Drug Combinations