Restoring ceftolozane susceptibility: a role for diazabicyclooctane β-lactamase inhibitors?

Paired baseline and post-exposure isolates from 34 patients who developed ceftolozane–tazobactam (TOL-TAZ) resistance following treatment of multidrug-resistant (MDR) Pseudomonas aeruginosa infections were analyzed to determine if ceftolozane with an alternative β-lactamase inhibitor could restore susceptibility. The median baseline TOL-TAZ MIC was 2 mg/L; 88% of post-exposure isolates harbored new ampC mutations. Median MIC fold-increase from baseline was 32-, 24-, 16-, and 6-fold for ceftolozane–tazobactam, ceftolozane–avibactam (AVI), ceftolozane–relebactam (REL), and ceftolozane–durlobactam (DUR), respectively. Enhanced ceftolozane–durlobactam activity was evident in specific ampC mutations.