title: Contemporary diversity of β-lactamases among Enterobacteriaceae in the nine U.S. census regions and ceftazidime-avibactam activity tested against isolates producing the most prevalent β-lactamase groups.
abstract: Escherichia 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. pneumoniae strains]) 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 Enterobacteriaceae have been documented, and ceftazidime-avibactam was very active against the vast majority of β-lactamase-producing strains isolated from U.S. hospitals.
authors.affiliation: JMI Laboratories, North Liberty, Iowa, USA.
authors.forename: Mariana
authors.initials: M
authors.lastname: Castanheira
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Farrell
authors.forename: Kevin M
authors.initials: KM
authors.lastname: Krause
authors.forename: Ronald N
authors.initials: RN
authors.lastname: Jones
authors.forename: Helio S
authors.initials: HS
authors.lastname: Sader
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D002442:Ceftazidime / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004756:Enterobacteriaceae Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D015870:Gene Expression; D014644:Genetic Variation; D006801:Humans; D041121:Klebsiella oxytoca / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008997:Monobactams / Q000627:therapeutic use*; D010957:Plasmids; D011513:Proteus mirabilis / Q000187:drug effects / Q000201:enzymology / Q000235:genetics; D000078304:Tigecycline; D014481:United States / Q000453:epidemiology; D018440:beta-Lactam Resistance / Q000187:drug effects / Q000235:genetics*; D001618:beta-Lactamases / Q000235:genetics* / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D008997:Monobactams; D000078304:Tigecycline; C041078:ceftazidime monobactam; D002442:Ceftazidime; D001618:beta-Lactamases; D008911:Minocycline