Evaluation of In Vitro Activity of Ceftolozane/Tazobactam and Ceftazidime/Avibactam Against Carbapenem-Resistant Pseudomonas aeruginosa Strains and Mechanisms of Carbapenem Resistance: Data from Tertiary Care Hospital

Background: Carbapenem-resistant Pseudomonas aeruginosa is an endemic problem in several countries, notably Turkey. Objectives: This study aimed to investigate the underlying mechanisms contributing to the carbapenem resistance phenotype and enhance the in-vitro activity of ceftolozane-tazobactam (C/T) and ceftazidime-avibactam (C/A) against carbapenem-resistant P. aeruginosa strains. Methods: A total of 114 carbapenem-resistant P. aeruginosa strains were isolated from different types of clinical specimens. The tested antibiotics were evaluated using the antibiotic disk diffusion method. Additionally, C/T and C/A were tested using the gradient test method. The efficacy of phenylalanine-arginine-β-naphthylamide (PAβN) as efflux pump inhibitors was assessed to determine their ability to reduce meropenem minimum inhibitory concentrations. Polymerase chain reaction (PCR) assays were conducted to identify blaIMP, blaVIM, and blaNDM-1. Results: Among 114 strains of carbapenem-resistant P. aeruginosa, overall resistance rates for C/T and C/A were 10.7% and 8.8%, respectively. Efflux pump inhibitor-based antibiotic susceptibility testing indicated that 35.08% of strains showed resistance modulated by PAβN. Among the strains, 27 (24.5%) were found to produce metallo-beta-lactamase (MBL), with blaVIM (17 strains, 14.91%) being the most common, followed by blaIMP (12 strains, 10.53%). Conclusions: Emerging carbapenem resistance in P. aeruginosa strains is a serious therapeutic challenge for clinicians. Carbapenem resistance can be influenced by various factors, some of which were not assessed in our study. Nonetheless, our results revealed that the main mechanism associated with carbapenem-resistant P. aeruginosa strains is a PAβN-sensitive efflux pump. Among acquired MBLs, VIM-type enzymes were found to be the most prevalent.