title: Lessons from an outbreak of metallo-β-lactamase-producing Klebsiella oxytoca in an intensive care unit: the importance of time at risk and combination therapy.
abstract: BACKGROUND
  Outbreaks of nosocomial infection due to carbapenem-resistant Enterobacteriaceae (CRE), mostly Klebsiella spp., have become a worldwide phenomenon.
  
  
  OBJECTIVE
  To investigate the risk factors for the acquisition of clonal multidrug-resistant Klebsiella oxytoca (MDRKO) producing the metallo-β-lactamase IMP-8 and hyperproducing chromosomal OXY-2 β-lactamase during a well-characterized outbreak, and to describe the clinical features of infections due to MDRKO.
  
  
  METHODS
  A four-wave outbreak due to MDRKO occurred in the intensive care unit of a Spanish hospital between 2009 and 2011. The risk factors for acquisition of MDRKO during waves 1 and 2 (in which colonized patients served as the main reservoir for the epidemic strain) were analysed using a case-control study by Cox regression and logistic regression analysis. Clinical data and treatments of patients infected with MDRKO were also analysed.
  
  
  RESULTS
  For the study of risk factors, 26 cases and 45 controls were studied. None of the variables studied in the Cox regression analysis showed an association with MDRKO acquisition; time at risk was the only associated variable by logistic regression analysis. Colonization pressure was not associated with earlier acquisition. Overall, 14 patients were infected with MDRKO; ventilator-associated pneumonia (seven patients) was the most frequent type of infection. Monotherapy tended to be associated with higher mortality than combination therapy [60% (3/5) vs 16.6% (1/6); P = 0.07].
  
  
  CONCLUSIONS
  Time at risk was the most significant risk determinant for the acquisition of carbapenem-resistant Enterobacteriaceae (CRE) in this epidemiological context and should be included in any study of risk factors for the acquisition of multidrug-resistant bacteria. Combination therapy may be superior to monotherapy for the treatment of CRE infections.
authors.affiliation: Internal Medicine Service, Hospital La Merced, Osuna, Seville, Spain. Electronic address: vergara_lopez@hotmail.com.
authors.forename: S
authors.initials: S
authors.lastname: Vergara-López
authors.affiliation: Laboratory of Microbiology, Hospital La Merced, Osuna, Seville, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Domínguez
authors.affiliation: Department of Microbiology, University of Seville, Seville, Spain.
authors.forename: M C
authors.initials: MC
authors.lastname: Conejo
authors.affiliation: Department of Microbiology, University of Seville, Seville, Spain; Infectious Diseases and Clinical Microbiology Unit, University Hospital Virgen Macarena, Seville, Spain.
authors.forename: Á
authors.initials: Á
authors.lastname: Pascual
authors.affiliation: Infectious Diseases and Clinical Microbiology Unit, University Hospital Virgen Macarena, Seville, Spain; Department of Medicine, University of Seville, Seville, Spain.
authors.forename: J
authors.initials: J
authors.lastname: Rodríguez-Baño
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D003428:Cross Infection / Q000188:drug therapy* / Q000453:epidemiology / Q000382:microbiology*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000453:epidemiology* / Q000382:microbiology; D041121:Klebsiella oxytoca / Q000201:enzymology / Q000302:isolation & purification*; D008297:Male; D008875:Middle Aged; D016016:Proportional Hazards Models; D011446:Prospective Studies; D013030:Spain / Q000453:epidemiology; D013997:Time Factors; D018440:beta-Lactam Resistance; D001618:beta-Lactamases / Q000096:biosynthesis
chemical_list: D000900:Anti-Bacterial Agents; D001618:beta-Lactamases
keywords: Carbapenem-resistant Enterobacteriaceae; Klebsiella oxytoca; Outbreak; Time at risk