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Restoring ceftolozane susceptibility: a role for diazabicyclooctane β-lactamase inhibitors?
Ava J Dorazio1, Ellen G Kline1, Kevin M Squires1
1Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
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.
