Efficacy of erythromycin lactobionate for treating Pseudomonas aeruginosa bacteremia in mice

Abstract

We induced endogenous Pseudomonas aeruginosa bacteremia by administering cyclophosphamide and ampicillin to specific pathogen-free mice fed P. aeruginosa. Using this model, we evaluated the efficacy of erythromycin lactobionate (EML) in treating P. aeruginosa bacteremia. Treatment with EML at 50 and 100 mg/kg of body weight per day twice a day for 14 days significantly increased the survival rate. The most effective dose was 100 mg/kg/day, with a survival rate of 80%o compared with a 20%o survival rate in the control. However, the administration of EML at 500 mg/kg/day rather decreased the survival rate. In a model of intravenous infection, treatment with EML at 100 mg/kg/day twice a day for 7 days before the bacterial challenge also enhanced the survival rate. EML levels in serum, liver, and stool were apparently lower than the MIC (512 pg/ml). These observations suggest that EML is effective against P. aeruginosa bacteremia despite a lack of specific activity for this pathogen. Although the protective mechanism is still unclear, it is possible that a subinhibitory level of EML may affect the virulence of P. aeruginosa and enhance the host defense system.

Efficacy of Bacteriophage Therapy against Gut-Derived Sepsis Caused by Pseudomonas aeruginosa in Mice

“…This model incorporates the oral inoculation of bacteria, subsequent bacterial colonization, overgrowth in the intestinal tract, and invasion of the bloodstream. We believe that this animal model closely resembles the clinical pathophysiology of septicemia in humans (13).…”

“…After bacterial translocation was demonstrated experimentally (5,9), bacteria in the gastrointestinal tract came to be regarded as an important pathogenic factor in immunocompromised patients, such as those undergoing anticancer chemotherapy. We therefore developed a murine model of gut-derived sepsis caused by P. aeruginosa (13,14,(19)(20)(21)(22)(23). This model incorporates the oral inoculation of bacteria, subsequent bacterial colonization, overgrowth in the intestinal tract, and invasion of the bloodstream.…”

“…In this model, the inoculated P. aeruginosa organisms crossed the gastrointestinal mucosal barrier after overgrowth in the intestinal tract and spread systemically by a process termed bacterial translocation (5,9). By using this model, we were able to examine the therapeutic efficacy of phage strain KPP10 against a P. aeruginosa-induced gut-derived sepsis model that closely mimics the clinical pathophysiology of septicemia in humans (13).…”

“…P. aeruginosa strain D4 was isolated from the blood of a neutropenic mouse with bacteremia (13) and was stored at Ϫ80°C in heart-brain broth (Difco Laboratories, Detroit, MI) containing 15% glycerol.…”

“…However, the models used in those studies were simple models of infection that did not closely resemble the pathophysiologies of diseases in humans. We induced gut-derived sepsis caused by P. aeruginosa by administering cyclophosphamide and ampicillin to specificpathogen-free mice fed P. aeruginosa (13,14,(19)(20)(21)(22)(23). In this model, the inoculated P. aeruginosa organisms crossed the gastrointestinal mucosal barrier after overgrowth in the intestinal tract and spread systemically by a process termed bacterial translocation (5,9).…”