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Ceftazidime-avibactam (MIC50/90 , 0.12/0.25 μg/ml) inhibited 99.9% (20,698/20,709) ofEnterobacteriaceae isolates 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 &gt;8 μg/ml, three wereK. pneumoniae strains producing metallo-β-lactamases (all ceftazidime-avibactam MICs, &gt;32 μg/ml), with two NDM-1 producers and oneK. pneumoniae strain carrying thebla KPC-2 andbla VIM-4 genes. 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.

antimicrobial agents and chemotherapy

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