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Antimicrob. Agents Chemother. doi:10.1128/AAC.00635-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Efficacy of Bacteriophage Therapy against Pseudomonas aeruginosa gut-derived Sepsis in Mice

Third Department of Surgery, Toho University School of Medicine, Department of Microbiology, Tokyo Medical University, Department of Respiratory Medicine, Toho University Omori Medical Center, Department of Microbiology and Infectious Diseases, Toho University School of Medicine, Department of Molecular Microbiology and Infections, Kochi Medical School

^* To whom correspondence should be addressed. Email: tetsuya{at}tokyo-med.ac.jp,

	Abstract

We evaluated the efficacy of bacteriophage (phage) therapy by using a murine Pseudomonas aeruginosa gut-derived sepsis model that closely resembles the clinical pathophysiology of septicemia in humans. Oral administration of a newly isolated lytic phage strain KPP10 significantly protected mice against mortality (survival rate: 66.7% in phage-treated group vs. 0% in saline-treated control group; P < 0.01). Mice treated with phage also had a lower number of viable P. aeruginosa in blood, liver, and spleen. Inflammatory cytokines (TNF-, IL-1, and IL-6) in blood and liver were significantly lower in phage-treated mice than in phage-untreated mice. The number of viable P. aeruginosa in fecal matter in the gastrointestinal tract was significantly lower in phage-treated mice than in saline-treated control mice. We also studied the efficacy of phage treatment for intraperitoneal infection with P. aeruginosa, and found that phage treatment significantly improved the survival of mice, but only under limited experimental conditions. In conclusion, our findings suggest that oral administration of phage may be effective against gut-derived sepsis caused by P. aeruginosa.

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