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Background  Healthcare-associated infections caused by  Klebsiella pneumoniae  isolates are increasing and few effective antibiotics are currently available to treat patients. We observed decreased carbapenem susceptibility among  K. pneumoniae  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  K. pneumoniae  and to determine the antimicrobial resistance mechanisms.    Methods  Risk factors associated with carbapenem-resistant  K. pneumoniae  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  K. pneumoniae  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.    Results  Sixty patients were included (20 cases and 40 controls) in the study. Mortality was higher for patients with carbapenem-resistant  K. pneumoniae  infections compared with those with carbapenem-susceptible  K. pneumoniae  (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  bla  CTX-M-2,  an extended-spectrum betalactamase gene. In addition, a single isolate also possessed  bla  GES-1.  Genes encoding plasmid-mediated AmpC beta-lactamases or carbapenemases (KPC, metallo-betalactamases or OXA-carbapenemases) were not detected.    Conclusions  The  K. pneumoniae  multidrug-resistant organisms were associated with significant mortality. The mechanisms associated with decreased  K. pneumoniae  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.

bmc infectious diseases

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