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) 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 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 mutations.