In vitro activity of ceftolozane/tazobactam against multidrug-resistant Pseudomonas aeruginosa from patients in Western Europe: SMART 2017-2020

Int J Antimicrob Agents. 2023 May;61(5):106772. doi: 10.1016/j.ijantimicag.2023.106772. Epub 2023 Mar 4.

Abstract

Multidrug-resistant (MDR) Pseudomonas aeruginosa infections compromise both empirical and definitive antimicrobial therapies. The Study for Monitoring Antimicrobial Resistance Trends (SMART) surveillance program identified 943 MDR P. aeruginosa (from a total of 4086 P. aeruginosa isolates [23.1%]) collected at 32 clinical laboratories in six countries in Western Europe from 2017 to 2020. Minimum inhibitory concentrations (MICs) for ceftolozane/tazobactam and 10 comparator agents were determined by broth microdilution and interpreted using 2021 EUCAST breakpoints. β-lactamase genes were identified in selected isolate subsets. Most isolates of P. aeruginosa in Western Europe (93.3%) were ceftolozane/tazobactam-susceptible. A total of 23.1% of P. aeruginosa isolates were MDR. Of these, 72.0% were ceftolozane/tazobactam-susceptible, which is similar to that for ceftazidime/avibactam (73.6%) but >40% higher than for carbapenems, piperacillin/tazobactam, third- and fourth-generation cephalosporins, and levofloxacin. Metallo-β-lactamases (MBLs) were carried by 8.8% of molecularly characterized MDR P. aeruginosa, and 7.6% of molecularly characterized MDR isolates carried Guiana Extended Spectrum (GES) carbapenemases. MBLs were identified in isolates from all six countries, ranging from 3.2% of all P. aeruginosa isolates from Italy to 0.4% of all isolates from the United Kingdom. Acquired β-lactamases were not identified in 80.0% of molecularly characterized MDR P. aeruginosa isolates. Percentages of MDR isolates without detected β-lactamases were higher in the United Kingdom (97.7%), Spain (88.2%), France (88.1%), and Germany (84.7%) than in Portugal (63.0%) and Italy (61.3%), where carbapenemases were more prevalent. Ceftolozane/tazobactam is an important treatment option for patients infected with MDR P. aeruginosa that are not susceptible to first-line antipseudomonal agents.

Keywords: Ceftolozane/tazobactam; MDR; Multidrug-resistance; Pseudomonas aeruginosa; SMART; Surveillance; Western Europe.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Anti-Infective Agents* / pharmacology
  • Ceftazidime / pharmacology
  • Cephalosporins / pharmacology
  • Cephalosporins / therapeutic use
  • Drug Resistance, Multiple, Bacterial / genetics
  • Humans
  • Microbial Sensitivity Tests
  • Penicillanic Acid / therapeutic use
  • Pseudomonas Infections* / drug therapy
  • Pseudomonas Infections* / epidemiology
  • Pseudomonas aeruginosa
  • Tazobactam / pharmacology
  • Tazobactam / therapeutic use
  • beta-Lactamases / pharmacology

Substances

  • ceftolozane
  • Anti-Bacterial Agents
  • Penicillanic Acid
  • Cephalosporins
  • ceftolozane, tazobactam drug combination
  • Tazobactam
  • Ceftazidime
  • Anti-Infective Agents
  • beta-Lactamases