Combined bacteriophages and antibiotics as an efficient therapy against VRE Enterococcus faecalis in a mouse model

Res Microbiol. 2018 Nov;169(9):531-539. doi: 10.1016/j.resmic.2018.04.008. Epub 2018 May 16.

Abstract

Clinical applications of bacteriophage therapy have been recently gathering significant attention worldwide, used mostly as rescue therapy in cases of near-fatal antibiotic failure. Thus, clinically relevant in-vivo models presenting both short- and long-term implications of phage therapy given as rescue treatment for fulminant infections are of highest importance. In this study, a cocktail consisting of two lytic bacteriophages was used to evaluate the therapeutic efficacy of phage therapy as a rescue treatment for severe septic peritonitis in a mouse model. We established that a single injection of the bacteriophage cocktail was sufficient to completely reverse a 100% mortality trend caused by Vancomycin-Resistant Enterococcus faecalis, with significant improvement in both the clinical state and laboratory test results, and without harmful effects on the microbiome. The combination of bacteriophages with a suboptimal antibiotic regimen imparts an additional beneficial effect on the treatment success.

Keywords: EFDG1; EFLK1; Mouse peritonitis model; Phage therapy; Phage-antibiotic combination; VRE Enterococcus faecalis.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / therapeutic use*
  • Bacteriophages / physiology*
  • Disease Models, Animal
  • Drug Therapy, Combination / methods
  • Enterococcus faecalis / drug effects*
  • Enterococcus faecalis / growth & development
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gram-Positive Bacterial Infections / therapy*
  • Mice
  • Peritonitis / microbiology
  • Peritonitis / therapy
  • Phage Therapy / adverse effects
  • Phage Therapy / methods*
  • Stem Cells

Substances

  • Anti-Bacterial Agents