In Vitro Selection of Enterobacter cloacae with Cefepime, Meropenem, and Ceftazidime-avibactam Generate Diverse Resistance Mechanisms

We submitted 5 E. cloacae isolates to 10-day serial passage in broth microdilution with cefepime, meropenem, or ceftazidime-avibactam to evaluate MIC increases and resistance mechanisms after exposure. Post-exposure isolates displaying >2-fold changes from the parent isolate and the parent isolate were analyzed. MIC changes increased 4- to 64-fold (median: 32-fold) after cefepime, 16- to 64-fold (16-fold) after meropenem and 2- to 32-fold (8-fold) after ceftazidime-avibactam exposure. Post-exposure isolates had diverse mechanisms identified using a combination of short- and long-read whole genome sequencing