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

• Published in: International journal of antimicrobial agents 2023-05, Vol.61 (5), p.106772-106772, Article 106772
• Main Authors: Karlowsky, James A., Lob, Sibylle H., Siddiqui, Fakhar, Akrich, Brune, DeRyke, C. Andrew, Young, Katherine, Motyl, Mary R., Hawser, Stephen P., Sahm, Daniel F.
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Anti-Infective Agents - pharmacology; antibiotic resistance; beta-lactamase; beta-Lactamases - pharmacology; carbapenems; ceftazidime; Ceftazidime - pharmacology; Ceftolozane/tazobactam; Cephalosporins - pharmacology; Cephalosporins - therapeutic use; Drug Resistance, Multiple, Bacterial - genetics; France; Germany; Humans; Italy; levofloxacin; MDR; Microbial Sensitivity Tests; minimum inhibitory concentration; monitoring; Multidrug-resistance; multiple drug resistance; Penicillanic Acid - therapeutic use; piperacillin; Portugal; Pseudomonas aeruginosa; Pseudomonas Infections - drug therapy; Pseudomonas Infections - epidemiology; SMART; Spain; Surveillance; Tazobactam - pharmacology; Tazobactam - therapeutic use; United Kingdom; Western Europe; Western European region
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2023.106772

•93.3% of Pseudomonas aeruginosa from Western Europe were ceftolozane/tazobactam-susceptible•23.1% of P. aeruginosa from Western Europe were multidrug-resistant (MDR)•72% of MDR P. aeruginosa in Western Europe were ceftolozane/tazobactam-susceptible•∼30% of MDR P. aeruginosa in Western Europe were meropenem- or imipenem-susceptible•16.6% of MDR P. aeruginosa carried a carbapenemase (8.8% MBL, 7.6% GES, 0.2% GPC) 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.