The effect of double-carbapenem therapy on mortality rates and microbiological cure rates in patients diagnosed with carbapenem-resistant Klebsiella pneumoniae infections in comparison to monotherapy and currently used combinations of antibiotics

Abstract

Introduction: Infection with the bacteria carpamenease-producing Klebsiella pneumoniae represents a significant cause of mortality in hospitalised patients. These multidrug resistant bacteria are resistant to currently used antibiotics as a result of carbapenemase production. Dual carbapenem therapy has been proposed as a valid therapeutic option, this therapy combines two carbapenem antibiotics, with one acting as a suicide inhibitor allowing the subsequent carbapenem to exert a bactericidal effect. Aim: The aim of this meta-analysis was to determine if dual carbapenem therapy had a significant effect on mortality rate and microbiological cure rate in patients diagnosed with carbapenemase-producing Klebsiella pneumoniae infections in comparison to standard antibiotic therapies. Methods: The search terms “(dual OR double) carbapenem (therapy OR treatment) AND klebsiella pneumoniae” were used to search databases and inclusion and exclusion criteria were applied to retrieved papers, a total of seven studies were identified for inclusion in the meta-analysis. The quality of included studies was assessed using the cochrane tool for risk of bias assessment and funnel plots were produced to determine the influence of publication bias. A random effects model was used to assess the outcomes; mortality rate and microbiological cure rate. Results and Conclusion: Dual carbapenem therapy had a time dependent effect on patient mortality rates. Dual carbapenem therapy significantly lowered  mortality rates in patients in comparison to standard antibiotic therapy, especially in comparison to monotherapy treatment regimens. Additionally, dual carbapenem therapy significantly improved microbiological cure rate in patients when compared to standard antibiotic treatment regimens demonstrating the possible clinical applications of a dual carbapenem antibiotic regimen in the treatment of carbapenemase-producing Klebsiella pneumoniae infections.