Antimicrobial activity of new anti-Pseudomonas beta-lactam-beta-lactamase inhibitors against Pseudomonas aeruginosa respiratory isolates recovered during the study for Monitoring Antimicrobial Resistance Trends (SMART) program in France (2016-2022)

Abstract

Objectives: To assess the susceptibility of ceftolozane/tazobactam (C/T) and comparators to Pseudomonas aeruginosa isolates recovered from respiratory-tract-infections (RTI) between 2016-2022 in the French SMART study.

Methods: Antibiotic susceptibility testing and minimum inhibitory concentrations (MICs) of 717 P.aeruginosa isolates collected in five French hospitals were determined and interpreted according to the EUCAST-2022 guidelines. P. aeruginosa isolates resistant (R) to imipenem and/or C/T were screened by PCR for extended-spectrum-β-lactamases (ESBLs), AmpC and carbapenemase genes. The identified genes were sequenced and the variants determined.

Results: All in all, 96.5 % of P. aeruginosa isolates were susceptible to C/T, comparable to the susceptibilities of meropenem-vaborbactam (MVB = 96.5 %), imipenem/relebactam (IMI/REL = 96.9 %) and ceftazidime-avibactam (C/A = 97.0 %). MIC₅₀ and MIC₉₀ for C/T were 0.5 and 2 mg/L respectively against the 717 isolates. Among the 242 isolates (33.7 %) resistant to at least one anti-Pseudomonas β-lactam, close to 90 % were susceptible to C/T, C/A, MVB and IMI/REL. Among the 80 isolates resistant to piperacillin-tazobactam, cefepime and ceftazidime, 76.3 % were susceptible to C/T and only IMI/REL and amikacin reached susceptibility exceeding 80 %. Among the 32 isolates resistant to imipenem and meropenem, susceptibility exceeding 60 % was observed only for IMI/REL, C/T, and C/A. For these strains, the MIC₅₀ of C/T was 2 mg/L, while that of C/A was at the resistance threshold (8 mg/L). IMI/REL had the strongest activity (72 %) against the 25 isolates resistant to C/T. Lastly, 53 imipenem and/or C/T-R isolates harbored a class C β-lactam (blaPDC) variant, and one of them also carried the bla_PER-1 gene and another, the bla_VIM-2 gene.

Conclusion: C/T is a reliable treatment option in RTI caused by P. aeruginosa.

Keywords: Antimicrobial susceptibility; Ceftolozane/tazobactam; Pseudomonas aeruginosa; Respiratory tract infection; SMART study (Study for Monitoring Antimicrobial Resistance Trends).