Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying Collected in U.S. Hospitals from 2012 to 2015.

carbapenemase (KPC)-producing isolates have been increasingly reported worldwide, and therapeutic options to treat infections caused by these organisms are limited. We evaluated the activity of ceftazidime-avibactam and comparators against 456 isolates carrying collected from 79 U.S. hospitals during 2012 to 2015. Overall, ceftazidime-avibactam (MIC, 0.5/2 μg/ml; 99.3% susceptible) and tigecycline (MIC, 0.5/1 μg/ml; 98.9% susceptible at ≤2 μg/ml) were the most active agents. Only 80.5% and 59.0% of isolates were susceptible to colistin and amikacin, respectively. All three isolates (0.7%) displaying resistance to ceftazidime-avibactam (; MICs, ≥16 μg/ml) were evaluated using whole-genome sequencing analysis and relative quantification of expression levels of porins and efflux pump. Two isolates carried metallo-β-lactamase genes, or , among other β-lactam resistance mechanisms, and one displayed a premature stop codon in and decreased expression of Ceftazidime-avibactam was active against 100.0 and 99.3% of isolates carrying ( = 221) and ( = 145), respectively. Isolates carrying were more commonly recovered from pneumonia ( = 155), urinary tract ( = 93), and skin/soft tissue ( = 74) infections. Ceftazidime-avibactam (97.8 to 100.0% susceptible) was consistently active against isolates from all infection sites. (83.3% of the collection) susceptibility rates were 99.2% for ceftazidime-avibactam, 98.9% for tigecycline, and 80.1% for colistin. Ceftazidime-avibactam susceptibility did not vary substantially when comparing isolates from intensive care unit (ICU) patients to those from non-ICU patients. Ceftazidime-avibactam was active against this large collection of isolates carrying and represents a valuable addition to the armamentarium currently available for the treatment of infections caused by KPC-producing .