A Systematic Review and Meta-Analysis of the Clinical Efficacy and Safety of Bacteriophages in Bacterial Infections

The growing number of infections caused by multidrug-resistant bacteria (MDR) makes the development of alternative therapeutic strategies a priority of modern medicine. Bacteriophage therapy is considered as a promising method for the treatment of resistant infections; however, a systematic synthesis of clinical data remains an urgent task. The purpose of this review is to systematically summarize clinical data on bacteriophage therapy in humans and estimate the proportion of patients with clinical improvement. A systematic search was performed in the PubMed/MEDLINE, Embase, and Cochrane CENTRAL databases (January 2000 - February 2026). Randomized controlled trials (RCTs), cohort studies, case series, and compassionate use studies with ≥3 participants were included. Primary outcome – percentage of patients with clinical improvement. The meta-analysis was performed using a random effects model (DerSimonian–Laird method, logit transformation, Hartung–Knapp correction). The risk of systematic error was assessed using the RoB 2 (for RCTs) and ROBINS-I (for non-randomized studies) instruments. The review was carried out in accordance with the PRISMA 2020 guidelines. As a result, the final analysis included 17 studies (683 patients; 9 RCTs, 1 randomized uncontrolled study, and 7 nonrandomized studies) from more than 10 countries. The most studied pathogens were Pseudomonas aeruginosa, Staphylococcus aureus and Escherichia coli. The pooled proportion of patients with clinical improvement was 57.2% (95% CI: 35.9–76.1%; k=8, N=393), with high heterogeneity (I²=88.2%; prediction interval: 10.7–93.7%). In the leave-one-out analysis, the pooled proportion ranged from 52.6% to 63.1%. The reviewed publications did not report any serious adverse events with a confirmed relationship to phage administration. Four RCTs had a low risk of bias. In conclusion, published studies showed acceptable tolerability of bacteriophage therapy, with no reports of phage-related serious adverse events, and evidence suggestive of clinical benefit, particularly as an adjunct to antibiotic therapy for MDR infections. High heterogeneity, the predominance of uncontrolled study designs, and the noncomparative nature of the pooled estimate preclude conclusions about the efficacy of phage therapy relative to standard treatment. Large multicenter RCTs with standardized outcomes and systematic recording of adverse events are needed, along with standardization of the pharmaceutical quality of phage preparations.