Ceftazidime-avibactam (MIC 50/90, 0.12/0.25 μg/ml) inhibited 99.9% (20,698/20,709) of Enterobacteriaceae isolates at ≤8 μg/ml. This compound was active against resistant subsets, including ceftazidime-nonsusceptible Enterobacter cloacae (MIC 50/90, 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 776 Escherichia coli (12.0% for this species; MIC 50/90, 0.12/0.25 μg/ml), 721 Klebsiella pneumoniae (16.3%; MIC 50/90, 0.12/0.25 μg/ml), 119 Klebsiella oxytoca (10.3%; MIC 50/90, 0.06/0.25 μ/ml), and 80 Proteus mirabilis (4.9%; MIC 50/90, 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 (MIC 50/90, 0.5/2 μg/ml) and tigecycline (MIC 50/90, 0.5/1 μg/ml; 98.3% susceptible) were the most active agents against these strains. Meropenem (MIC 50/90, ≤0.06/≤0.06 μg/ml) and ceftazidime-avibactam (MIC 50/90, 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 were K. pneumoniae strains producing metallo-β-lactamases (all ceftazidime-avibactam MICs, >32 μg/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 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.
CITATION STYLE
Castanheira, M., Mills, J. C., Costello, S. E., Jones, R. N., & Sader, H. S. (2015). Ceftazidime-avibactam activity tested against Enterobacteriaceae isolates from U.S. hospitals (2011 to 2013) and characterization of β-lactamase-producing strains. Antimicrobial Agents and Chemotherapy, 59(6), 3509–3517. https://doi.org/10.1128/AAC.00163-15
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