Ceftolozane + diazabicyclooctane
Paired baseline and post-exposure isolates from 34 patients who developed ceftolozane-tazobactam resistance following treatment of MDR Pseudomonas infections were analyzed to determine if combining ceftolozane with an alternative beta-lactamase inhibitor could restore susceptibility. Eighty-eight percent of post-exposure isolates harbored new ampC mutations. The median minimum inhibitory concentration (MIC) fold-increase from baseline was 32-fold for ceftolozane-tazobactam. By comparison, MICs were increased by 24-, 16-, and 6-fold for ceftolozane-avibactam, ceftolozane-relebactam, and ceftolozane-durlobactam, respectively. Durlobactam demonstrated greater inhibitory activity than avibactam or relebactam; however, results varied by specific ampC mutation.