שנה שפה:

Bacteriophage Therapy Resolves Resistant Bacterial Sepsis: Proof of Concept



Daniel Gelman1, Ronen Hazan1, Shunit Coppenhagen-Glazer1, Vanda Lerrer1, Shaul Beyth2
1 Faculty of Dental Medicine, Hebrew University, Jerusalem, Israel
2 Orthopedic Surgery, Hadassah Medical Center, Jerusalem, Israel

Abdominal peritonitis is a life threatening condition worsened by multi-drug resistant bacteria. We chose this in-vivo model to serve in a proof-of-concept assay treating non-enteric resistant infection as a step in our effort to present a novel effective treatment for periprosthetic infections in orthopedics.

In this study a cocktail of two lytic bacteriophages was used to evaluate the therapeutic efficacy of phage therapy to resolve severe mouse septic peritonitis induced highly antibiotic resistantstrains. The assay was carried out on female ICR mice which were infected with intraperitoneal injection containing high inoculum (10*LD50) of Vancomycin-Resistant strain of Enterococcus faecalis. The mice were divided into several groups treated using our bacteriophage cocktail, both individually or in combination with standard antibiotic regimen. The mice were evaluated by clinical and laboratory findings, and bacterial load counts were obtained from numerous tissues.

A single intraperitoneal injection of the presented bacteriophage cocktail was sufficient to resolve and to rescue up to 100% cases of severe septic peritonitis, in mice that otherwise reached their humane end point within only 24 hours. Phage therapy also revealed an advantage in the survival rates and in the clinical evaluation of the mice over antibiotic regimen, while in some modalities the combination of the two led to the best clinical behavior and eradicated bacterial loads almost completely.

The effect on bacteria and bacteriophages administered to the mice and later retrieved from their tissues were evaluated, including changes in resistance profiles and effects on the bacteria-bacteriophage interactions, and will be discussed.

Our data supplies an in-vivo proof for the ability of phage therapy to resolve severe resistant bacterial septic peritonitis using single therapeutic dose, and specifically reveals the high therapeutic effect of our cocktail against VRE infections. This model opens a set of new opportunities in the in-vivo study of Phage Therapy.

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