A hospital-based matched case–control study to identify clinical outcome and risk factors associated with carbapenem-resistant <it>Klebsiella pneumoniae</it> infection

• Main Authors: Correa Luci, Martino Marines Dalla Valle, Siqueira Itacy, Pasternak Jacyr, Gales Ana Cristina, Silva Claudia Vallone, Camargo Thiago Zinsly Sampaio, Scherer Patricia Faria, Marra Alexandre Rodrigues
• Format: Article
• Language: English
• Published: BMC 2013-02-01
• Series: BMC Infectious Diseases
• Subjects: Klebsiella pneumoniae; Carbapenem-resistant <it>Klebsiella</it>; Healthcare associated infections; <it>Klebsiella</it> infections/microbiology; <it>Klebsiella</it> infections/mortality
• Online Access: http://www.biomedcentral.com/1471-2334/13/80

<p>Abstract</p> <p>Background</p> <p>Healthcare-associated infections caused by <it>Klebsiella pneumoniae</it> isolates are increasing and few effective antibiotics are currently available to treat patients. We observed decreased carbapenem susceptibility among <it>K. pneumoniae</it> isolated from patients at a tertiary private hospital that showed a phenotype compatible with carbapenemase production although this group of enzymes was not detected in any sample. The aim of this study was to describe the epidemiology and clinical outcomes associated with carbapenem-resistant <it>K. pneumoniae</it> and to determine the antimicrobial resistance mechanisms.</p> <p>Methods</p> <p>Risk factors associated with carbapenem-resistant <it>K. pneumoniae</it> infections were investigated by a matched case–control study from January 2006 through August 2008. A cohort study was also performed to evaluate the association between carbapenem resistance and in-hospital mortality. Bacterial identification and antimicrobial susceptibility were determined by Vitek 2 and Etest. Carbapenemase activity was detected using spectrophotometric assays. Production of beta-lactamases and alterations in genes encoding <it>K. pneumoniae</it> outer membrane proteins, OmpK35 and OmpK36, were analyzed by PCR and DNA sequencing, as well as SDS-Page. Genetic relatedness of carbapenem resistant isolates was evaluated by Pulsed Field Gel Electrophoresis.</p> <p>Results</p> <p>Sixty patients were included (20 cases and 40 controls) in the study. Mortality was higher for patients with carbapenem-resistant <it>K. pneumoniae</it> infections compared with those with carbapenem-susceptible <it>K. pneumoniae</it> (50.0% vs 25.7%). The length of central venous catheter use was independently associated with carbapenem resistance in the multivariable analysis. All strains, except one, carried <it>bla</it>_CTX-M-2, an extended-spectrum betalactamase gene. In addition, a single isolate also possessed <it>bla</it>_GES-1. Genes encoding plasmid-mediated AmpC beta-lactamases or carbapenemases (KPC, metallo-betalactamases or OXA-carbapenemases) were not detected.</p> <p>Conclusions</p> <p>The <it>K. pneumoniae</it> multidrug-resistant organisms were associated with significant mortality. The mechanisms associated with decreased <it>K. pneumoniae</it> carbapenem susceptibility were likely due to the presence of cephalosporinases coupled with porin alterations, which resulted from the presence of the insertion sequences in the outer membrane encoding genes.</p>