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Objective: To describe the epidemiology of and clinical outcomes associated with KPN with decreased carbapenem susceptibility and to determine the resistance mechanisms.
Methods: To identify risk factors associated with carbapenem-resistant KPN infection a matched case-control study was performed in a 620-bed private tertiary hospital in São Paulo, Brazil. All patients older than 18 years with KPN nosocomial infection during the period from January 1, 2006 to August 31, 2008 were identified. Case patients with carbapenem-resistant KPN infection were compared with control subjects with carbapenem-susceptible KPN. Matching was performed at a ratio of 1:2 according to date, acquisition unit and site of infection. A cohort study was carried out to evaluate the association between carbapenem resistance and in-hospital mortality, analyzing all patients (case and control subjects). Twenty strains of KPN were screened for the presence of beta-lactamases (Klebsiella pneumoniae carbapenemase - KPC, GES, CTX-M, OXA-Carbapenemase, plasmid-mediated AmpC and metallo-beta-lactamase - MBL) by using PCR and porin modifications (ompK35 and ompK36) in order to identify the mechanisms responsible for the carbapenem resistance. The bacterial identification and antimicrobial susceptibility test of these isolates were determined by Vitek 2 automated system and Etest. Additionally the MICs were confirmed by agar dilution. Pulsed field gel eletrophoresis (PFGE) were also performed.
Results: Sixty patients were included in our study (20 cases and 40 controls). Mortality was 27.5% and 50.0% for patients with carbapenem susceptible and resistant KPN, respectively (p=0.085). Univariate analysis showed that prior corticosteroid use (p=0.05), high APACHE score (p=0.004), CVC utilization (p=0.02) and previous exposure to carbapenem (p=0.02) were associated with carbapenem resistant KPN infection. The presence of cephalosporinases with porin modifications probably resulted by the presence of insertion sequences were the mechanisms associated with decreased carbapenem susceptibility. We observed 7 distinct PFGE patterns.
Conclusions: These multidrug-resistant organisms were associated with significant mortality. Limiting use of carbapenem may be an effective strategy to prevent these infections.