Assessment of in vitro antimicrobial activities of ceftolozane/tazobactam and ceftazidime/avibactam against carbapenem-resistant Pseudomonas aeruginosa clinical isolates

Abstract

Background: Carbapenem resistant Pseudomonas aeruginosa (P. aeruginosa) is a global health concern that poses a challenge to treat in health care facilities. Ceftazidim/avibactam and ceftolozane/tazobactam have a potential role in treatment of multi-drug resistant phenotypes including carbapenem resistant P. aeruginosa. Therefore, we aimed to assess the in vitro antimicrobial activity of ceftazidime/avibactam and ceftolozane/tazobactam against carbapenem-resistant P. aeruginosa (CRPA) strains with different β-lactamase/carbapenemase genes. Methods: Sixty CRPA isolates identified from clinical samples were examined for antimicrobial susceptibility including ceftazidim/avibactam and ceftolozane/tazobactam by Vitek2 compact system, and carbapenemase production by modified carbapenem inactivation method (mCIM) test and carbapenemase producing genes by polymerase chain reaction (PCR). Results: Isolates were resistant to imipenem in 96.7% and meropenem in 88.3%. of isolates. Carbapenemase production by mCIM test was 70% compared to 73.3% by (PCR). Carbapenemase encoding genes blaNDM, blaVIM and blaOXA-48 were detected in 60%, 41.7% and 25% respectively while blaIMP and blaKPC weren’t identified in this study. Among CRPA, both ceftazidim/avibactam and ceftolozane/tazobactam; were sensitive in only 11.7% of the isolates. Resistance to ceftazidim/avibactam and ceftolozane/tazobactam in isolates owning blaNDM, blaVIM, blaOXA-48 and those having combined blaNDM, blaVIM and blaOXA-48 carbapenemase resistance genes were 97.2%, 92%, 100% and 100% respectively. Conclusion: Modified carbapenem inactivation method test gave satisfactory results and could be used as an alternative to expensive genotypic methods. Ceftazidim/avibactam and ceftolozane/tazobactam were unsuccessful against carbapenem resistant P. aeruginosa isolates carrying carbapenemase genes especially metallo-β lactamase genes. Therefore, it is essential to detect susceptibility patterns to newly introduced β-Lactam/β-Lactamase inhibitor combinations due to the emerging resistance to these therapeutics.