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

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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 bla NDM, bla VIM and bla OXA-48 were detected in 60%, 41.7% and 25% respectively while bla IMP and bla KPC 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 bla NDM, bla VIM, bla OXA-48 and those having combined bla NDM, bla VIM and bla OXA-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.

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