Experimental Phage Therapy in TreatingKlebsiella pneumoniae-Mediated Liver Abscesses and Bacteremia in Mice

Abstract

ABSTRACTIntragastric inoculation of mice withKlebsiella pneumoniaecan cause liver abscesses, necrosis of liver tissues, and bacteremia. A newly isolated phage (φNK5) with lytic activity forK. pneumoniaewas used to treatK. pneumoniaeinfection in an intragastric model. Both intraperitoneal and intragastric administration of a single dose of φNK5 lower than 2 × 108PFU at 30 min afterK. pneumoniaeinfection was able to protect mice from death in a dose-dependent manner, but the efficacy achieved with a low dose of φNK5 by intragastric treatment provided the more significant protection. Phage φNK5 administered as late as 24 h afterK. pneumoniaeinoculation was still protective, while intraperitoneal treatment with phage was more efficient than intragastric treatment as a result of the dissemination of bacteria into the circulation at 24 h postinfection. Surveys of bacterial counts for mice treated with φNK5 by the intraperitoneal route revealed that the bacteria were eliminated effectively from both blood and liver tissue.K. pneumoniae-induced liver injury, such as liver necrosis, as well as blood levels of aspartate aminotransferase and alanine aminotransferase and inflammatory cytokine production, was significantly inhibited by φNK5 treatment. These data suggest that a low dose of φNK5 is a potential therapeutic agent forK. pneumoniae-induced liver infection.