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

Background: Outbreaks of nosocomial infection due to carbapenem-resistant Enterobacteriaceae (CRE), mostly Klebsiella spp., have become a worldwide phenomenon. Aim: To investigate the risk factors for the acquisition of clonal multidrug-resistant Klebsiella oxytoca (MDRKO) producing the metallo-beta-lactamase IMP-8 and hyperproducing chromosomal OXY-2 beta-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. Findings: 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. (C) 2014 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.