Multicenter Evaluation of Ceftazidime-avibactam and Ceftolozane-tazobactam Inhibitory Activity against Meropenem Non-Susceptible P. aeruginosa from Blood, Respiratory Tract and Wounds [PublishAheadOfPrint]

The recent escalation of carbapenem-resistant Pseudomonas aeruginosa has been recognized globally and threatens to erode the widespread clinical utility of this class of compounds for this prevalent healthcare associate pathogen. Herein, we compared the in-vitro inhibitory activity of ceftazidime-avibactam and ceftolozane-tazobactam against 290 meropenem non-susceptible Pseudomonas aeruginosa non-duplicate clinical isolates from 34 US hospitals using reference broth microdilution methods. Ceftazidime-avibactam and ceftolozane-tazobactam were active, with ceftolozane-tazobactam having significantly higher inhibitory activity than ceftazidime-avibactam. The heightened inhibitory activity of ceftolozane-tazobactam was sustained when the site of origin (respiratory, blood or wound) and non-susceptibility to other β-lactam antimicrobials was considered. An extensive genotypic search for enzymatically-driven β-lactam resistance mechanisms revealed the exclusive presence of VIM among only 4% of the subset of isolates non-susceptible to ceftazidime-avibactam, ceftolozane-tazobactam or both. These findings suggest an important role for both ceftazidime-avibactam and ceftolozane-tazobactam against carbapenem non-susceptible Pseudomonas aeruginosa. Further in-vitro and in-vivo studies are needed to better define the clinical utility of these novel therapies against the increasingly prevalent threat of multi-drug resistant Pseudomonas aeruginosa.

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