In Vitro Activity of Ceftolozane/tazobactam and Ceftazidime/avibactam Against Carbapenemase-producing Pseudomonas aeruginosa

Abstract

Introduction: The emergence of multidrug-resistant (MDR) and extensively drug-resistant strains of Pseudomonas aeruginosa in recent years has become a major issue due to treatment difficulties as well as high morbidity and mortality rates. Treatment options for infections caused by these microorganisms are very limited. Ceftolozane/tazobactam (C/T) and ceftazidime/avibactam (CZA) are recently developed cephalosporin/beta-lactamase inhibitor combinations for the treatment of infections caused by MDR P. aeruginosa strains. The aim of this study was to investigate the in vitro efficacy of C/T and CZA against MDR P. aeruginosa strains and to compare the in vitro efficacy of these two drugs. Materials and Methods: Thirty-two MDR P. aeruginosa isolates were included in the study. Identification and antimicrobial susceptibilities of the strains were performed using a VITEK 2® automated system. The efficacy of CZA and C/T was determined by the gradient strip test (Liofilchem MIC strip test, Italy). Modified carbapenemase inactivation method was used to detect carbapenemase production in all strains. Results: Rates of antibiotic resistance in the isolates were 78% for amikacin, 96.8% for levofloxacin, 90.6% for ciprofloxacin, 71.8% for gentamicin, and 78% for netilmicin. Ceftazidime/avibactam resistance was detected in 7 (21.8%) of the isolates and C/T resistance in 10 (31.2%). All strains with resistance to CZA also had resistance to C/T. Three strains were resistant to C/T but susceptible to CZA. Carbapenemase production was positive in all strains. Conclusion: The results of this study indicate that CZA and C/T may be an alternative treatment for some of the carbapenem-resistant P. aeruginosa infections. Further in vitro and in vivo studies are needed to evaluate the effectiveness of these new treatment options against the increasing threat of MDR P. aeruginosa.

Keywords

• colistin
• epidemiology
• hospital-acquired infections
• salvage therapy
• extended-spectrum beta-lactamases