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

Ceftazidime-avibactam (MIC50/90, 0.12/0.25 mu g/ml) inhibited 99.9% (20,698/20,709) of Enterobacteriaceae isolates at <= 8 mu g/ml. This compound was active against resistant subsets, including ceftazidime-nonsusceptible Enterobacter cloacae (MIC50/90, 0.25/0.5 mu g/ml) and extended-spectrum beta-lactamase (ESBL) phenotype isolates. An ESBL phenotype was noted among 12.4% (1,696/13,692 isolates from targeted species) of the isolates, including 776 Escherichia coli (12.0% for this species; MIC50/90, 0.12/0.25 mu g/ml), 721 Klebsiella pneumoniae (16.3%; MIC50/90, 0.12/0.25 mu g/ml), 119 Klebsiella oxytoca (10.3%; MIC50/90, 0.06/0.25 mu g/ml), and 80 Proteus mirabilis (4.9%; MIC50/90, 0.06/0.12 mu g/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 mu g/ml) and tigecycline (MIC50/90, 0.5/1 mu g/ml; 98.3% susceptible) were the most active agents against these strains. Meropenem (MIC50/90, <= 0.06/<= 0.06 mu g/ml) and ceftazidime-avibactam (MIC50/90, 0.12/0.25 mu g/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 mu g/ml,three were K. pneumoniae strains producing metallo-beta-lactamases (all ceftazidime-avibactam MICs, > 32 mu g/ml), with two NDM-1 producers and one K. pneumoniae strain carrying the bla(KPC-2) and bla(VIM-4) genes. Therapeutic options for isolates producing beta-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.