Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo‐controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers

Abstract

Bacteriophage therapy is a commonly used treatment for Staphylococcus aureus infections in countries of the former Soviet Union, using both single phages and phage cocktails. The scarce data available on Eastern phage cocktails prompted an investigation into commercially-available Pyophage cocktails from two different manufacturers used to treat skin and wound infections. Comparison of the metagenomic composition of two Pyophage products from Georgia and Russia revealed substantial differences in phage-types targeting Escherichia, Enterococcus, Salmonella, Pseudomonas aeruginosa and Proteus, therefore indicating multiple strategies for composing phage cocktails against these bacterial pathogens. Closely-related Kayvirus-like Myoviruses were, however, a shared component against S. aureus within all products, except for the inclusion of a secondary S. aureus Podovirus in one Microgen cocktail. Metagenomic analysis also revealed the presence of several probable prophage sequences but detected no genetic safety risks in terms of virulence factors or antibiotic resistance genes. The safety of broad-spectrum cocktails was tested by comparing the effects of nasal and oral exposure to Eliava Pyophage, a monospecies counterpart and placebo in healthy human carriers of S. aureus. The lack of adverse effects in any treatment groups supports the clinical safety of S. aureus phages administered as a single phage or as phage cocktail.