Practical applications of bacteriophage therapy: Biofilms to bedside

As the golden age of antibiotics crumbles away in the face of untreatable bacterial infections arising globally, novel, safe, and adaptable therapies are essential. Bacteriophages, co-discovered over 100 years ago by Félix d’Herelle, were widely utilized before the antibiotic era. Unable to compete with antibiotics in terms of price, manufacturing ease, and safety, phage use was largely terminated in the West, though clinical use has continued in the Eastern bloc. With rampant fears of a post-antibiotic era, phage has gained traction in the West and appears the ideal weapon to employ alongside and in conjunction with antibiotics. Up to 80% of human infections are caused by bacterial biofilms, and select phages have been reported to break up these bacterial cities via polysaccharide depolymerases and lysins, though quorum sensing can reduce phage receptors and increase resistance. Phage antibiotic synergy has been observed with specific antibiotic classes, where low levels of antibiotics cause bacterial filamentation and increased bacterial killing by phage. What has arisen from numerous animal infection models is that early treatment (post-infection) is critical to phage efficacy. With phage now being recognized as part of the human microbiome, the anti-inflammatory and apparent tolerized immune response to bacteriophage is fitting, though there are inflammatory concerns with increased endotoxin levels remaining following phage purification. Recent clinical studies using phage against a vast array of infections highlight the translational promise of this therapy.