In vitro activity of ceftolozane-tazobactam and ceftazidime-avibactam against clinical isolates of meropenem-non-susceptible Pseudomonas aeruginosa: A two-centre study

Abstract

Objectives: This study aimed to compare the activity of ceftazidime-avibactam (C/A), ceftolozane-tazobactam (C/T) and three anti-pseudomonal β-lactams (piperacillin-tazobactam, ceftazidime and cefepime) against a collection of meropenem-non-susceptible Pseudomonas aeruginosa (P. aeruginosa) clinical isolates recovered from two centres in Turkey.

Methods: A total of 102 unique patient isolates of meropenem-non-susceptible P. aeruginosa were included in the study. MICs of antimicrobials were determined by the gradient diffusion method.

Results: Overall susceptibility rates for C/A and C/T were 83.3% and 82.4%, respectively. Both C/A and C/T had better activity than any one of the three anti-pseudomonal β-lactams. According to the MIC₅₀ values, C/T was the most potent agent against isolates. Although the susceptibility rates of isolates to C/T and C/A were similar, C/T (MIC₅₀, 1 μg/mL) was four-fold more potent than C/A (MIC₅₀, 4 μg/mL). The MIC₅₀ values of C/A and C/T for the isolates that were non-susceptible to three β-lactams were significantly higher than those for isolates that were non-susceptible to zero, one or two β-lactams. Also, the C/A MIC₅₀ value for the isolates that were non-susceptible to two β-lactams was higher than that for isolates which were non-susceptible to one β-lactam.

Conclusions: C/A and C/T showed good activity against meropenem-non-susceptible P. aeruginosa isolates. However, resistance to these agents was not uncommon among these isolates. The overall β-lactam susceptibility profile of isolates seems to have an effect on the probability of susceptibility to C/A and C/T. Antimicrobial susceptibility testing should be performed for C/A and C/T if these agents are considered for treatment of infections caused by meropenem-non-susceptible P. aeruginosa.

Keywords: Carbapenem-resistant Pseudomonas aeruginosa; Ceftazidime–avibactam; Ceftolozane–tazobactam; Meropenem-non-susceptible Pseudomonas aeruginosa; Meropenem-resistant; Pseudomonas aeruginosa.