Antimicrobial susceptibility profile of ceftolozane/tazobactam, ceftazidime/avibactam and cefiderocol against carbapenem-resistant Pseudomonas aeruginosa clinical isolates from Türkiye

Carbapenem resistant Pseudomonas aeruginosa (CR-PA) is escalating worldwide and leaves clinicians few therapeutic options in recent years, β-lactam/β-lactamase inhibitor combinations (ceftolozane-tazobactam, ceftazidime-avibactam) and a new siderophore cephalosporin (cefiderocol) have been approved for the treatment of P. aeruginosa infection and have shown potent activity against isolates defined as carbapenem resistant. The aim of this study was to determine the phenotypic profile of these agents against CR-PA in the emerging setting of carbapenemases.

CR-PA clinical isolates were collected from three teaching hospitals in different geographical regions between January 2017-December 2021. All isolates were subjected to phenotypic carbapenemase testing using modified carbapenem inactivation method. MICs were determined by reference broth microdilution and evaluated according to EUCAST standards, while genotypic profiling was determined using PCR methods.

244 CR-PA sourced most frequently from the respiratory tract (32.2%), blood (20.4%) and urine (17.5%) were evaluated. Of all isolates, 32 (13.1%) were phenotypically and 38 (15.6%) were genotypically defined as carbapenemase-positive. The most common carbapenemase was GES (63.1%), followed by VIM (15.8%). The MIC_50/90(S%) of ceftazidime/avibactam, ceftolozane/tazobactam and cefiderocol in all CR-PA isolates were 4 and 32 (80%), 1 and > 64 (69%) and 0.25 and 1 mg/L (96%), respectively. Cefiderocol was also the most active agent in carbapenemase-positive isolates (90%).

While ceftolozane/tazobactam and ceftazidime/avibactam remained highly active against CR-PA devoid of carbapenemases, cefiderocol provided potent in vitro activity irrespective of carbapenemase production. When considering the potential clinical utility of newer agents against CR-PA, regional variations in carbapenemase prevalence must be considered.