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

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.

Targeting Enterococcus faecalis biofilms with phage therapy.

Phage therapy has been proven to be more effective, in some cases, than conventional antibiotics, especially regarding multidrug-resistant biofilm infections. The objective here was to isolate an anti-Enterococcus faecalis bacteriophage and to evaluate its efficacy against planktonic and biofilm cultures. E. faecalis is an important pathogen found in many infections, including endocarditis and persistent infections associated with root canal treatment failure. The difficulty in E. faecalis treatment has been attributed to the lack of anti-infective strategies to eradicate its biofilm and to the frequent emergence of multidrug-resistant strains. To this end, an anti-E. faecalis and E. faecium phage, termed EFDG1, was isolated from sewage effluents. The phage was visualized by electron microscopy. EFDG1 coding sequences and phylogeny were determined by whole genome sequencing (GenBank accession number KP339049), revealing it belongs to the Spounavirinae subfamily of the Myoviridae phages, which includes promising candidates for therapy against Gram-positive pathogens. This analysis also showed that the EFDG1 genome does not contain apparent harmful genes. EFDG1 antibacterial efficacy was evaluated in vitro against planktonic and biofilm cultures, showing effective lytic activity against various E. faecalis and E. faecium isolates, regardless of their antibiotic resistance profile. In addition, EFDG1 efficiently prevented ex vivo E. faecalis root canal infection. These findings suggest that phage therapy using EFDG1 might be efficacious to prevent E. faecalis infection after root canal treatment.