Non-antibiotic and adjunctive therapies for Pseudomonas aeruginosa wound infections: a systematic review

Abstarct Background Pseudomonas aeruginosa is a major cause of difficult-to-treat wound and burn infections, driven by biofilm formation and increasing antimicrobial resistance. Non-antibiotic strategies may offer alternatives or adjuncts to conventional therapy, but their clinical value remains uncertain. Methods Ovid MEDLINE, PubMed and Web of Science databases were searched from inception to 2 July 2026 for in vivo mammalian and human studies evaluating non-antibiotic therapies for P. aeruginosa-infected wounds. Eligible studies assessed bacterial burden and/or wound-healing outcomes. Risk of bias was evaluated using RoB 2, ROBINS-I, or SYRCLE, according to study design. Owing to substantial heterogeneity in models, interventions, dosing, comparators, and outcome measures, findings were synthesised qualitatively. Results Twenty-eight studies evaluating seven therapeutic categories were included: bacteriophages, quorum-sensing inhibitors, photodynamic therapy, nitric oxide-based therapies, silver nanoparticles, honey, and acetic acid. Most interventions reduced P. aeruginosa burden, and several also accelerated wound closure or improved histological healing. Adjunctive approaches, particularly bacteriophage–antibiotic combinations, nitric oxide delivery systems, and selected quorum-sensing inhibitors, showed notable promise. Acetic acid had the strongest direct human evidence for bacterial clearance, whereas evidence for several newer approaches remained predominantly preclinical. Across the literature, microbiological improvement did not consistently translate into proportional wound healing. Interpretation was limited by small sample sizes, heterogeneous outcome measures, sparse controlled human data, incomplete assessment of biofilm, and frequent concerns regarding randomisation, allocation concealment, and blinding. Conclusions Non-antibiotic therapies show meaningful potential as adjuncts for P. aeruginosa wound infection, but the evidence is not yet sufficient to support routine replacement of established antimicrobial treatment. Standardised wound and biofilm outcomes, clinically representative resistant isolates, and adequately powered human trials are needed to identify which approaches can deliver durable clinical benefit.