Colistin resistance increases 28-day mortality in bloodstream infections due to carbapenem-resistant Klebsiella pneumoniae

Mortality due to K. pneumoniae bacteremia is on rise, particularly in regions with high rates of carbapenem and colistin resistance. We aimed to define risk factors for colistin resistance and its impact on mortality. Patients diagnosed with carbapenem-resistant K. pneumoniae (CRKp) bacteremia between 2014 and 2018 were divided into two groups as colistin susceptible (ColS) and colistin resistant (ColR) based on broth microdilution method. Retrospective case-control study was conducted to compare characteristics and outcomes. Multiple logistic regression model was used to define independent risk factors for acquired colistin resistance and Cox proportional hazard model for 28-day mortality. A total of 82 patients (39 ColS and 43 ColR) were included. Mean age was 61.5 years, and 50 (61%) were male. Colistin resistance was significantly increased with duration of hospital stay (p = 0.007) and prior colistin use (p = 0.007). Overall, the 28-day mortality rate was 66%. Age (p = 0.014) and colistin resistance significantly increased 28-day (p = 0.009) mortality. Microbiological response to treatment within 7 days favors survival. PFGE analysis revealed an outbreak with K. pneumoniae ST78 and ST45 clones. Patients treated with combined antimicrobials had significantly lower 28-day mortality (p = 0.045) in comparison to monotherapy. However, types of combinations did not show significant superiority on each other. Colistin resistance increases 28-day mortality in CRKp bacteremia. Although combined regimens are more effective than monotherapy, existing antibacterial combinations have no apparent superiority to each other. New treatment options are pivotal.

Automated summary

Mortality due to K. pneumoniae bacteremia is increasing, especially in regions with high resistance to carbapenem and colistin. Risk factors for colistin resistance and its impact on mortality were studied in patients with CRKp bacteremia. Colistin resistance was associated with hospital stay duration and prior colistin use, and significantly increased 28-day mortality along with age. Combined antimicrobial therapy was found to be more effective than monotherapy in reducing mortality in CRKp bacteremia.