title: OXA-181-producing Klebsiella pneumoniae establishing in Singapore.
abstract: BACKGROUND
  Carbapenemase producing Enterobacteriaceae are becoming a major public health concern globally, however, relatively little is known about the molecular and clinical epidemiology of these organisms in many parts of the world.
  
  
  METHODS
  As part of a laboratory surveillance programme, 96 carbapenem non-susceptible Enterobacteriaceae isolates from clinical samples from patients in seven hospitals were referred for investigation for carbapenemases. Using polymerase chain reaction (PCR) to screen for a collection of genes encoding carbapenemases, 33 of 96 (34.5%) isolates were confirmed as carbapenemase producers. NDM-1 producers were the most prevalent at 64% (21/33) whilst OXA-181 was the second most common carbapenemase constituting 24.5% (8/33) of the carbapenemase producing isolates. Seven of these eight OXA-181 positive isolates underwent further characterisation with screening for other transmissible antimicrobial resistance determinants using PCR. Clonal relatedness was explored using Multilocus sequence typing (MLST) and Pulsed Field Gel Electrophoresis (PFGE). Plasmid characterisation was performed including restriction analysis and transfer by conjugation or transformation.
  
  
  RESULTS
  In addition to the OXA-181 gene, all contained other transmissible resistance determinants including extended spectrum β-lactamases, oxacillinases or 16S rRNA methylase genes, but none contained metallo-β-lactamases or serine carbapenemases. All isolates had a multidrug resistant phenotype with two isolates being resistant to every antibiotic tested including colistin. Multilocus sequence typing confirmed five isolates belonged to ST17 and two to ST14, with those belonging to the same sequence type having identical PFGE profiles. The OXA-181 gene was typically carried on large plasmids which were mostly non-conjugative.
  
  
  CONCLUSIONS
  OXA-181 carbapenemase appears to be an important and probably under-recognised cause of carbapenem resistance in Enterobacteriaceae in Singapore. Further coordinated research into clinical and molecular epidemiology of carbapenemases is urgently required in Singapore and throughout Asia.
authors: Department of Laboratory Medicine, National University Health System, 5 Lower Kent Ridge Road, Singapore, 119074, Singapore. michelle.balm@gmail.com
authors: Michelle N D
authors: MN
authors: Balm
authors: Grace
authors: G
authors: Ngan
authors: Roland
authors: R
authors: Jureen
authors: Raymond T P
authors: RT
authors: Lin
authors: Jeanette W P
authors: JW
authors: Teo
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001426:Bacterial Proteins / Q000096:biosynthesis* / Q000235:genetics; D004251:DNA Transposable Elements; D024881:Drug Resistance, Bacterial; D006801:Humans; D007710:Klebsiella Infections / Q000453:epidemiology; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D012846:Singapore / Q000453:epidemiology; D001618:beta-Lactamases / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004251:DNA Transposable Elements; D001618:beta-Lactamases; C063912:carbapenemase
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