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ABSTRACTEscherichia coli(328 isolates), Klebsiella pneumoniae(296), Klebsiella oxytoca(44), and Proteus mirabilis(33) isolates collected during 2012 from the nine U.S. census regions and displaying extended-spectrum-β-lactamase (ESBL) phenotypes were evaluated for the presence of β-lactamase genes, and antimicrobial susceptibility profiles were analyzed. The highest ESBL rates were noted for K. pneumoniae(16.0%, versus 4.8 to 11.9% for the other species) and in the Mid-Atlantic and West South Central census regions. CTX-M group 1 (including CTX-M-15) was detected in 303 strains and was widespread throughout the United States but was more prevalent in the West South Central, Mid-Atlantic, and East North Central regions. KPC producers (118 strains [112 K. pneumoniaestrains]) were detected in all regions and were most frequent in the Mid-Atlantic region (58 strains). Thirteen KPC producers also carried blaCTX-M. SHV genes encoding ESBL activity were detected among 176 isolates. Other β-lactamase genes observed were CTX-M group 9 (72 isolates), FOX (10), TEM ESBL (9), DHA (7), CTX-M group 2 (3), NDM-1 (2 [Colorado]), and CTX-M groups 8 and 25 (1). Additionally, 62.9% of isolates carried ≥2 β-lactamase genes. KPC producers were highly resistant to multiple agents, but ceftazidime-avibactam (MIC50/90, 0.5/2 μg/ml) and tigecycline (MIC50/90, 0.5/1 μg/ml) were the most active agents tested. Overall, meropenem (MIC50, ≤0.06 μg/ml), ceftazidime-avibactam (MIC50, 0.12 to 0.5 μg/ml), and tigecycline (MIC50, 0.12 to 2 μg/ml) were the most active antimicrobials when tested against this collection. NDM-1 producers were resistant to all β-lactams tested. The diversity and increasing prevalence of β-lactamase-producing Enterobacteriaceaehave been documented, and ceftazidime-avibactam was very active against the vast majority of β-lactamase-producing strains isolated from U.S. hospitals.

ABSTRACTEnterobacteriaceaebacteremia isolates (n= 195; 6.4% overall) collected from 26 U.S. hospitals located in 20 states were screened for various β-lactamase classes. A total of 175 isolates carried one to eight acquired β-lactamase genes of 44 types that were detected in 55 combinations. Eighty-five (43.6%) strains carried blaCTX-M, and blaCTX-M-15was the most prevalent (33.8%). Genes encoding OXA-1/30 (often associated with blaCTX-M-15), CMY-2, SHV extended-spectrum β-lactamase (ESBLs), and TEM-1 were also prevalent. Among 33 carbapenem-resistant strains, 28 carried blaKPC-2or blaKPC-3(17 and 11 strains, respectively), and those were recovered mostly in the New York City area (16 strains) and Houston, TX (9 strains). Fourteen new SHV variants were identified among Klebsiella pneumoniaeisolates carrying one or multiple SHV alleles, three carrying G238S and/or E240K amino acid alterations that confer ESBL activity. Only two of eight K. oxytocaisolates carried acquired β-lactamases, but most had mutations on the blaOXYpromoter region, and three new OXY-encoding genes were characterized. Concordance between a commercial nucleic acid-based microarray (Check-MDR CT101) and reference methods was noted for 105/109 (97.2%) strains. Thirty-two strains having genes that are not targeted by the commercial system were detected (OXA ESBLs, PER, PSE, or intrinsic genes). Overall, a great variety of enzymes were observed, with numerous strains carrying multiple genes. Rates of CTX-M-producing strains appear to be increasing in U.S. hospitals (26.6% in 2007 to 43.8% for 2010) participating in the SENTRY Program. Furthermore, the Check-Points system seems to be a reliable, robust, and user-friendly assay for detection of enzyme-mediated resistance.