title: Ceftazidime-avibactam activity tested against Enterobacteriaceae isolates from U.S. hospitals (2011 to 2013) and characterization of β-lactamase-producing strains.
abstract: Ceftazidime-avibactam (MIC50/90, 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 (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 776 Escherichia coli (12.0% for this species; MIC50/90, 0.12/0.25 μg/ml), 721 Klebsiella pneumoniae (16.3%; MIC50/90, 0.12/0.25 μg/ml), 119 Klebsiella oxytoca (10.3%; MIC50/90, 0.06/0.25 μg/ml), and 80 Proteus 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 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.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA mariana-castanheira@jmilabs.com.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Janet C
authors.initials: JC
authors.lastname: Mills
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Costello
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
mesh_terms: D053961:Azabicyclo Compounds / Q000494:pharmacology*; D002442:Ceftazidime / Q000494:pharmacology*; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000378:metabolism*; D004926:Escherichia coli / Q000187:drug effects / Q000378:metabolism; D041121:Klebsiella oxytoca / Q000187:drug effects / Q000378:metabolism; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000378:metabolism; D008826:Microbial Sensitivity Tests; D011513:Proteus mirabilis / Q000187:drug effects / Q000378:metabolism; D014481:United States; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D053961:Azabicyclo Compounds; C543519:avibactam; D002442:Ceftazidime; D001618:beta-Lactamases
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