Original article Risk factors for carbapenem-resistant Klebsiella pneumoniae infection/colonization: A caseecase-control study Diamantis P. Kofteridis a, * , Antonis Valachis a , Dimitra Dimopoulou a , Sofia Maraki b , Athanasia Christidou b , Elpis Mantadakis c , George Samonis a a Department of Internal Medicine, University Hospital of Heraklion, Crete, Greece b Department of Clinical Bacteriology, University Hospital of Heraklion, Crete, Greece c Department of Pediatrics, Democritus University of Thrace, Alexandroupolis, Thrace, Greece article info Article history: Received 16 September 2013 Received in revised form 7 November 2013 Accepted 9 November 2013 Keywords: Carbapenem-resistant Klebsiella pneumoniae Antimicrobial resistance Intensive care unit Renal disease abstract Carbapenem-resistant Klebsiella pneumoniae (CRKP) is increasingly reported worldwide. The aim of the present study was to identify risk factors associated with the development of CRKP infections. A retro- spective, caseecase-control study was performed at the University Hospital of Heraklion, Greece. The study population included 83 patients from whom CRKP was isolated, 79 from whom carbapenem- sensitive K. pneumoniae (CSKP) was isolated and 161 (control group) from whom K. pneumoniae was not isolated. The median age of CRKP and CSKP patients was 79 (28e101) and 80 (39e97) years, respectively, while that of the controls was 75 (18e100) years. K. pneumoniae was isolated predominantly from urine in both case groups, followed by blood. Independent risk factors for CRKP infection/coloni- zation were admission to ICU (p ¼ 0.004), prior surgical procedure (p ¼ 0.036) and presence of renal disease (p ¼ 0.037), while for CSKP were neurological disease (p ¼ 0.007), and older age (p ¼ 0.011). No association between CRKP and prior antimicrobial exposure was found. Of the entire cohort 40 patients (12%) died; 22 (27%) in the CRKP,12 (15%) in the CSKP and 6 (4%) in the control group. Isolation of any K. pneumoniae strain was associated with higher mortality compared to the control group (21% vs. 4%; p < 0.005). Mortality was not statistically different between those infected/colonized/with a CRKP or a CSKP strain (p ¼ 0.084). According to these results prior ICU stay, prior surgical procedure and renal disease were independent risk factors for the development of a CRKP infection/colonization. Ó 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. 1. Introduction Unfortunately, due to continuous exposure to carbapenems, Klebsiella pneumoniae strains resistant to carbapenems (Carbape- nem-resistant K. pneumoniae; CRKP) have emerged [1e 7], repre- senting a serious clinical problem, since the antimicrobial treatment options are very limited. These resistant strains have been the source of hospital-acquired infections in severely ill pa- tients, while mortality seems to be higher among those infected with such strains compared to patients infected with carbapenem susceptible K. pneumoniae (CSKP) [8]. What makes the situation even more difficult is that the gene that encodes carbapenemase, the enzyme mostly responsible for the carbapenem-resistance, resides on a transmissible plasmid that can be transferred to other Enterobacteriaceae [3,9]. As a result, identifying patients at risk of infections by CRKP can facilitate the choice and finally the efficacy of the empirical therapy. Additionally this knowledge is important for the design and the implementation of interventions aiming to reduce the spread of antimicrobial resistance [10]. The aim of the present study was to identify risk factors for the development of CRKP acquisition. For this goal, in order to overcome the limitations and potential biases associated with case control studies, as described in the literature [10e16] an alternative and reliable design was used, the caseecase-control study [9,17e19]. 2. Materials and methods 2.1. Hospital setting and study population This study was performed in the University Hospital of Her- aklion, the only tertiary hospital in the island of Crete, Greece. The microbiology laboratory database was searched to identify all * Corresponding author. Department of Internal Medicine, University Hospital of Heraklion, P.O. Box 1352, 71110 Heraklion, Crete, Greece. Tel.: þ30 2810 392359; fax: þ30 2810 392847. E-mail address: kofterid@med.uoc.gr (D.P. Kofteridis). Contents lists available at ScienceDirect Journal of Infection and Chemotherapy journal homepage: http://www.elsevier.com/locate/jic 1341-321X/$ e see front matter Ó 2013, Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.jiac.2013.11.007 J Infect Chemother 20 (2014) 293e297