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Combined effect of monoclonal antilipopolysaccharide antibody and ceftazidime in intranasal mice model of Klebsiella pneumoniae infection

Croatian Society of Natural Sciences
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Background and Purpose: The evolution of microorganisms in the sense of antimicrobial resistance is an emerging problem, especially in hospital settings. It seriously complicates the ability to combat severe infections. Bacteria of the genus Klebsiella are well known bacterial pathogens that cause a wide variety of infections. Numerous recent articles have reported the growing trend of antimicrobial resistance among clinical isolates of Klebsiella. Besides capsular antigen the most important virulence factor of genus Klebsiella is lipopolysaccharide (LPS). Therefore, previously generated antilipopolysaccharide monoclonal antibody for O1 antigen of Klebsiella pneumoniae was used in this study. The purpose of this study was to examine the existence of synergy between antilipopolysaccharide monoclonal antibody Ru-O1 (mAb Ru-O1) and ceftazidime in a model of lung Klebsiella infection. Materials and Methods: The study was conducted using Klebsiella pneumoniae strain Caroli (O1:K2) to inoculate BALB/c mice by intranasal route. Mice were lethally infected with the bacteria. The effects of mAb Ru-O1 and ceftazidime, as a single treatment protocol or in combination, were monitored on the survival of experimental animals. Results: The overall survival rates in groups pretreated only with mAb Ru-O1 prior to infection or treated only with ceftazidime 24 hours after infectionwere 33%. The outcome of infection was best in a group of mice that received both mAb and single dose of ceftazidime with overall survival rate of 66%. Conclusions: The study shows that the combination treatment with anti-LPS mAb Ru-O1 and ceftazidime in amice model of lethal Klebsiella pneumoniae pneumonia exerts synergistic effect and enhances the survival of experimental animals compared to animals treated with mAb Ru-O1 or ceftazidime alone.

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