Efficacy and Safety Outcomes of Bacteriophage Therapy for Resistant Bacterial Infections

Phage therapy, the therapeutic use of bacteriophages for multi-drug resistant bacterial infections, is an understudied treatment approach that has been receiving increased interest in recent years. With multiple different treatment strategies (e.g., oral vs. intravenous (IV)) as well as varying types of bacteriophage combinations (phage cocktails) that are possible, the effectiveness of these phage cocktails on certain bacterial infections, as well as overall safety, is in question. This systematic review aims to analyze current evidence on the efficacy and safety outcomes of bacteriophage therapy for resistant bacterial infections. A systematic search of PubMed, Embase, and Scopus was conducted to investigate clinical studies following guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Included studies addressed the efficacy of phage cocktails in bacterial-resistant infections with a secondary focus on safety and adverse events. Two independent reviewers assessed randomized controlled studies using the Cochrane Risk-of-Bias 2 (ROB-2) tool and Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. The three randomized controlled studies demonstrated low risk of bias, while the non-randomized controlled study showed a serious risk of bias. Patient outcomes and adverse events were narratively synthesized due to heterogeneity across study populations, pathogens, and treatment protocols. In total, only four studies met the scope of this review, which significantly limits the interpretation of the results. Two studies focused on Pseudomonas aeruginosa infections, while one study looked at Mycobacterium spp., and another study examined Helicobacter pylori infections known to hold some antibiotic resistance. Phage administration ranged from topical/aerosol for the P. aeruginosa infections, IV/aerosol for Mycobacterium spp., and oral for H. pylori. The two studies on P. aeruginosa demonstrated statistically significant reductions in bacterial presence, while the other two studies did not demonstrate statistically significant results. Regarding safety, no study reported any statistically significant severe adverse events. Two trials provided data on less severe adverse events, which were not statistically significant compared to the comparison groups. The trends synthesized from this study are limited by disease and therapeutic heterogeneity, sample size, and different treatment durations. Phage therapy shows early promise for drug-resistant infections, particularly P. aeruginosa, with a favorable safety profile. However, due to therapeutic and disease heterogeneity, small sample sizes, and variable treatment durations, larger dedicated trials are needed.