Phage Therapy in the 21st Century: Is There Modern, Clinical Evidence of Phage-Mediated Efficacy?

Abstract

Many bacteriophages are obligate killers of bacteria. That this property could be medically useful was first recognized over one hundred years ago, with 2021 being the 100-year anniversary of the first clinical phage therapy publication. Here we consider modern use of phages in clinical settings. Our aim is to answer one question: do phages serve as effective anti-bacterial infection agents when used clinically? An important emphasis of our analyses is on whether phage therapy-associated anti-bacterial infection efficacy can be reasonably distinguished from that associated with often coadministered antibiotics. We find that about half of 70 human phage treatment reports—published in English thus far in the 2000s—are suggestive of phage-mediated anti-bacterial infection efficacy. Two of these are randomized, double-blinded, infection-treatment studies while 14 of those studies, in our opinion, provide superior evidence of a phage role in observed treatment successes. Roughly three-quarters of these potentially phage-mediated outcomes are based on microbiological as well as clinical results, with the rest based on clinical success. Since many of these phage treatments are of infections for which antibiotic therapy had not been successful, their collective effectiveness is suggestive of a valid utility in employing phages to treat otherwise difficult-to-cure bacterial infections.

Phage Products for Fighting Antimicrobial Resistance

“…It can treat the fibrosis and burn infections caused by P. aeruginosa [ 95 ]. It can treat urinary tract infections and IBD caused by E.coli and K. pneumonia [ 96 , 97 ]. Among the preclinical phage products, the cocktail products composed of 4–8 phage mixtures account for 60% of the total.…”

Treating Bacterial Infections with Bacteriophage-Based Enzybiotics: In Vitro, In Vivo and Clinical Application

“…For over 100 years, whole phages have been successfully applied to treat various bacterial infections [31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46][47]. This includes infections caused by pathogens belonging to infamous ESKAPE group (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp.)…”

Risk of Bacteriophage Therapeutics to Transfer Genetic Material and Contain Contaminants Beyond Endotoxins with Clinically Relevant Mitigation Strategies

“…It should be noted that chronic infections that have failed numerous conventional antibiotic regimens are the main type of infections that bacteriophage therapy is currently being used to treat. 33 With these recalcitrant infections, clinicians have ample time to test for these issues and, if needed, to devise mitigation strategies. In this section, testing of bacteriophage therapeutics for transduction capabilities and contaminants is discussed.…”