Clinical application of customized and non-customized bacteriophage therapy in patients with refractory/resistant...

Patients with refractory/resistant bacterial infections face high mortality rates. Bacteriophage therapy (PT) is a viable solution, but clinical evidence remains fragmented. This review synthesizes current evidence on PT efficacy, safety, and implementation, with additional analysis by customization strategies: non-customized, customized selection and customized production.

We examined clinical studies on PTs for refractory/resistant bacterial infections and pooled efficacy and safety outcomes by customization strategy from randomized controlled trials, observational studies, cohorts, case series and case reports using a random-effects model. Subset sensitivity analyses were conducted, and individual patient data were further analysed. Risk of bias was assessed for each study.

As of 14 May 2025, 16 226 articles were identified, and 130 studies (1115 patients) were included: 559 non-customized, 451 customized selection and 105 customized production. Risks of bias were low to serious. Clinical improvement (I² 87%) and bacterial eradication (I² 94%) rates were 71% (95% confidence interval [CI], 60-80) and 51% (95% CI 30-72), respectively. Customized production group had the highest success rates (79% and 87%), albeit at a cost. Time taken for customization often resulted in delays in PT. Higher titres and multiple administration routes were associated with better bacterial eradication. Efficacy improvement compared to control was statistically insignificant. Adverse events were mild to moderate. Phage neutralization appeared before, during, and after PT cessation. Impacts on pharmacokinetics remain uncertain. Immunological markers varied across studies.

PT shows promising clinical outcomes, but significant gaps in clinical evidence persist, warranting well-designed trials. Laboratory-based phage monitoring shows promise but requires systematic investigation.