Ceftolozane-tazobactam and ceftazidime-avibactam efficacy against K. pneumoniae: first NDM-5 and OXA-232 report from Türkiye

Abstract

Introduction: Ceftolozane-tazobactam (CLZ-TAZ) and ceftazidime-avibactam (CAZ-AVB) are recently developed β-lactam/β-lactamase inhibitor combinations active against resistant Gram-negative bacteria. This study compared the in vitro activities of ceftazidime, meropenem, piperacillin-tazobactam (PIP-TAZ), CLZ-TAZ, and CAZ-AVB in Klebsiella pneumoniae isolates from Hacettepe University hospitals and investigated the carbapenemase types detected over the past five years.

Methodology: A total of 550 K. pneumoniae isolates were collected consecutively from invasive clinical samples between 2015 and 2022 according to the SENTRY protocol. Identification was performed using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). Susceptibility testing for ceftazidime, meropenem, PIP-TAZ, CLZ-TAZ, and CAZ-AVB was carried out by broth microdilution and interpreted according to EUCAST standards. Carbapenemase genes were determined by whole-genome sequencing.

Results: Isolates were obtained from blood (n = 191), skin/soft tissue (n = 130), urine (n = 102), respiratory (n = 86), and intra-abdominal (n = 41) samples. Resistance rates were 62.3% for ceftazidime, 29.7% for meropenem, 60.4% for PIP-TAZ, 43.1% for CLZ-TAZ, and 8.7% for CAZ-AVB. The predominant carbapenemases were OXA-48, OXA-232, NDM-1, OXA-181, and KPC-2. Multiple carbapenemases coexisted in 10% of carbapenem-resistant isolates.

Conclusions: CAZ-AVB demonstrated superior activity compared to CLZ-TAZ in this high-resistance setting, While OXA-48 and NDM-1 remain the most frequent carbapenemases, emerging enzymes including OXA-181, OXA-232, KPC-3, and NDM-5 were also detected. The coexistence of multiple enzymes in single isolates highlights a growing therapeutic challenge, emphasizing the need for continued surveillance and effective antimicrobial stewardship.