Activity of Ceftazidime-Avibactam Against Clinical Isolates of Klebsiella pneumoniae, Including KPC-Carrying Isolates, Endemic to New York City.

In this report, we examined the (1) activity of ceftazidime-avibactam against clinical isolates Klebsiella pneumoniae, including those harboring blaKPC, (2) potential mechanisms leading to reduced susceptibility, and (3) activity of ceftazidime-avibactam when combined with other agents. Of 802 carbapenem-resistant isolates of K. pneumoniae gathered from New York City from 1999 to 2014, all were susceptible to ceftazidime-avibactam. Minimum inhibitory concentrations (MICs) were higher in isolates with K. pneumoniae, with the carbapenemase (KPC)-3 (compared to KPC-2), and those with a frameshift mutation in ompK35. MICs did not appear to be affected by changes in ompK36 or by expression of acrB. Time-kill experiments demonstrated synergy between either polymyxin B or amikacin and ceftazidime-avibactam in a minority of isolates. In conclusion, ceftazidime-avibactam is active against K. pneumoniae, including blaKPC isolates, in our region, but activity is affected by KPC subtype and by mutations in ompK35. Synergy can occur when combined with polymyxin B or amikacin, but is unpredictable.