Investigation of Carbapenemase Resistance Genes and Plasmid-Mediated Quinolone Resistance Genes in Ceftolozane/Tazobactam-Resistant Enterobacterales and Pseudomonas aeruginosa Isolates

Objectives: Carbapenem-resistant Gram-negative bacteria limit treatment options for hospital-acquired infections, and resistance to ceftolozane/tazobactam is increasingly reported. This study investigated the distribution of carbapenemase and plasmid-mediated quinolone resistance (PMQR) genes among ceftolozane/tazobactam-resistant Enterobacterales and Pseudomonas aeruginosa isolates. Methods: We analyzed 224 non-duplicate ceftolozane/tazobactam-resistant clinical isolates (145 Enterobacterales and 79 P. aeruginosa) collected at Ondokuz Mayıs University Faculty of Medicine Hospital between January 2024 and March 2025. Species were identified by MALDI-TOF MS, and minimum inhibitory concentrations were determined with the BD Phoenix system and interpreted according to EUCAST breakpoints (v15.0; resistant: >2 mg/L for Enterobacterales, >4 mg/L for P. aeruginosa). Carbapenemase (blaOXA-48, blaNDM, blaKPC, blaVIM, blaIMP) and PMQR (qnrA, qnrB, qnrC, qnrS) genes were detected by multiplex PCR. Results: Among Enterobacterales (82.8% Klebsiella pneumoniae), blaOXA-48 was the most frequent carbapenemase gene (50.3%), followed by blaNDM (25.5%) and blaKPC (17.2%); 24.8% of isolates carried none of the tested genes. qnrB was the most common PMQR gene (27.6%). Among P. aeruginosa, blaVIM (34.2%) and blaNDM(15.2%) were detected, and 51.9% of isolates were negative for all tested carbapenemase genes. PMQR genes were rare in P. aeruginosa (qnrB, 2.5%). blaIMP and qnrC were not detected in either group. Conclusions: Carbapenemase genes, mainly blaOXA-48 in Enterobacterales and blaVIM in P. aeruginosa, were common among ceftolozane/tazobactam-resistant isolates, but many isolates were negative for all tested genes, suggesting that other mechanisms are involved. Because only resistant isolates were studied, these findings describe gene distribution and do not establish its contribution to resistance. Continued molecular surveillance is needed to support local treatment and infection control decisions.