Assessment of the In Vitro Activity of Ceftazidime-Avibactam against Multidrug-Resistant Klebsiella spp. Collected in the INFORM Global Surveillance Study, 2012 to 2014

Increasing resistance in Gram-negative bacilli, including Klebsiella spp., has reduced the utility of broad-spectrum cephalosporins. Avibactam, a novel non-beta-lactam beta-lactamase inhibitor, protects beta-lactams from hydrolysis by Gram-negative bacteria that produce extended-spectrum beta-lactamases (ESBLs) and serine carbapenemases, including Ambler class A and/or class C and some class D enzymes. In this analysis, we report the in vitro activity of ceftazidime-avibactam and comparators against multi-drug-resistant (MDR) Klebsiella spp. from the 2012-2014 INFORM surveillance study. Isolates collected from 176 sites were sent to a central laboratory for confirmatory identification and tested for susceptibility to ceftazidime-avibactam and comparator agents, including ceftazidime alone. A total of 2,821 of 10,998 (25.7%) Klebsiella species isolates were classified as MDR, based on resistance to three or more classes of antimicrobials. Among the MDR isolates, 99.4% had an ESBL screen-positive phenotype, and 27.4% were not susceptible to meropenem as an example of a carbapenem. Ceftazidime-avibactam was highly active against MDR isolates, including ESBL-positive and serine carbapenemase-producing isolates, with MIC50/90 values of 0.5/2 mu g/ml and 96.6% of all MDR isolates and ESBL-positive MDR isolates inhibited at the FDA breakpoint (MIC value of <= 8 mu g/ml). Ceftazidime-avibactam did not inhibit isolates producing class B enzymes (metallo-beta-lactamases) either alone or in combination with other enzymes. These in vitro results support the continued investigation of ceftazidime-avibactam for the treatment of MDR Klebsiella species infections.