Ceftazidime-Avibactam Activity Tested against Enterobacteriaceae Isolates from U.S. Hospitals (2011 to 2013) and Characterization of β-Lactamase-Producing Strains

Abstract

ABSTRACTCeftazidime-avibactam (MIC50/90, 0.12/0.25 μg/ml) inhibited 99.9% (20,698/20,709) ofEnterobacteriaceaeisolates at ≤8 μg/ml. This compound was active against resistant subsets, including ceftazidime-nonsusceptibleEnterobacter cloacae(MIC50/90, 0.25/0.5 μg/ml) and extended-spectrum β-lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4% (1,696/13,692 isolates from targeted species) of the isolates, including 776Escherichia coli(12.0% for this species; MIC50/90, 0.12/0.25 μg/ml), 721Klebsiella pneumoniae(16.3%; MIC50/90, 0.12/0.25 μg/ml), 119Klebsiella oxytoca(10.3%; MIC50/90, 0.06/0.25 μg/ml), and 80Proteus mirabilis(4.9%; MIC50/90, 0.06/0.12 μg/ml) isolates. The most common enzymes detected among ESBL phenotype isolates from 2013 (n= 743) screened using a microarray-based assay were CTX-M-15-like (n= 307), KPC (n= 120), SHV ESBLs (n= 118), and CTX-M-14-like (n= 110). KPC producers were highly resistant to comparators, and ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml) and tigecycline (MIC50/90, 0.5/1 μg/ml; 98.3% susceptible) were the most active agents against these strains. Meropenem (MIC50/90, ≤0.06/≤0.06 μg/ml) and ceftazidime-avibactam (MIC50/90, 0.12/0.25 μg/ml) were active against CTX-M-producing isolates. Other enzymes were also observed, and ceftazidime-avibactam displayed good activity against the isolates producing less common enzymes. Among 11 isolates displaying ceftazidime-avibactam MIC values of >8 μg/ml, three wereK. pneumoniaestrains producing metallo-β-lactamases (all ceftazidime-avibactam MICs, >32 μg/ml), with two NDM-1 producers and oneK. pneumoniaestrain carrying theblaKPC-2andblaVIM-4genes. Therapeutic options for isolates producing β-lactamases may be limited, and ceftazidime-avibactam, which displayed good activity against strains, including those producing KPC enzymes, merits further study in infections where such organisms occur.