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

Luci Correa13*, Marines Dalla Valle Martino2, Itacy Siqueira2, Jacyr Pasternak2, Ana Cristina Gales3, Claudia Vallone Silva1, Thiago Zinsly Sampaio Camargo4, Patricia Faria Scherer4 and Alexandre Rodrigues Marra4

Author Affiliations

1 Infection Control Unit, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627/701 6º Andar Bloco D, São Paulo, ZIP 05652-000, Brazil

2 Laboratory of Microbiology, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627/701, São Paulo, ZIP 05651-901, Brazil

3 Division of Infectious Diseases, Universidade Federal de São Paulo (UNIFESP/EPM), Rua Napoleão de Barros, 715, 7º andar, São Paulo, ZIP 04024-002, Brazil

4 Intensive Care Unit, Hospital Israelita Albert Einstein, Av. Albert Einstein, 627/701, São Paulo, ZIP 05651-901, Brazil

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BMC Infectious Diseases 2013, 13:80  doi:10.1186/1471-2334-13-80

Published: 11 February 2013



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.


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.


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 blaCTX-M-2, an extended-spectrum betalactamase gene. In addition, a single isolate also possessed blaGES-1. Genes encoding plasmid-mediated AmpC beta-lactamases or carbapenemases (KPC, metallo-betalactamases or OXA-carbapenemases) were not detected.


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.

Klebsiella pneumoniae; Carbapenem-resistant Klebsiella; Healthcare associated infections; Klebsiella infections/microbiology; Klebsiella infections/mortality