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Klebsiella pneumoniae carbapenemase (KPC)-producingEnterobacteriaceae 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 456Enterobacteriaceae isolates carryingbla KPC collected from 79 U.S. hospitals during 2012 to 2015. Overall, ceftazidime-avibactam (MIC50/90 , 0.5/2 μg/ml; 99.3% susceptible) and tigecycline (MIC50/90 , 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 (K. pneumoniae ; 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,bla NDM-1 orbla VIM-4 , among other β-lactam resistance mechanisms, and one displayed a premature stop codon inompK35 and decreased expression ofompK36 . Ceftazidime-avibactam was active against 100.0 and 99.3% of isolates carryingbla KPC-3 (n = 221) andbla KPC-2 (n = 145), respectively. Isolates carryingbla KPC were more commonly recovered from pneumonia (n = 155), urinary tract (n = 93), and skin/soft tissue (n = 74) infections. Ceftazidime-avibactam (97.8 to 100.0% susceptible) was consistently active against isolates from all infection sites.K. pneumoniae (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 carryingbla KPC and represents a valuable addition to the armamentarium currently available for the treatment of infections caused by KPC-producingEnterobacteriaceae .

antimicrobial agents and chemotherapy

Low Frequency of Ceftazidime-Avibactam Resistance among Enterobacteriaceae Isolates Carrying <i>bla</i> <sub>KPC</sub> Collected in U.S. Hospitals from 2012 to 2015

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

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