Clinical evidence on nonantibiotic antibacterial strategies for reducing the risk of periprosthetic joint infection: a systematic review

Periprosthetic joint infection (PJI) remains one of the most devastating complications in orthopedic surgery, associated with substantial morbidity, high treatment costs, and increased mortality. Although antibiotic therapy remains the cornerstone of prevention and treatment, the emergence of antimicrobial resistance has driven the development of alternative antibacterial strategies targeting implant surfaces and the local biological environment. However, the clinical effectiveness of these nonantibiotic approaches has not yet been fully established. This systematic review and meta-analysis aimed to identify nonantibiotic antibacterial strategies currently applied in clinical practice, to evaluate their effectiveness in preventing or managing PJI and to quantify, through meta-analysis, the comparative infection-prevention effect of silver-coated versus uncoated prostheses. A systematic literature search was conducted in PubMed, Scopus, Web of Science, and Google Scholar following Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. The search was performed on 27 January 2026 and included studies published over the last 10 years (January 2015–December 2025). Eligible studies comprised clinical investigations assessing nonantibiotic antibacterial strategies in patients undergoing primary or revision orthopedic procedures. Interventions included antibacterial implant coatings, physicochemical surface modifications, and biologically based antimicrobial therapies. Primary outcomes were infection prevention/control, and reinfection; secondary outcomes included implant survival, adverse events, and function. Risk-of-bias was assessed with Cochrane Risk-of-Bias in Nonrandomized Studies of Interventions (ROBINS-I). Studies with extractable raw infection counts for silver-coated versus uncoated prostheses were pooled in a random-effects meta-analysis to estimate absolute risk reduction (ARR) and number needed to treat (NNT). Twenty-nine studies, including 2100 patients, met the inclusion criteria. Silver-coated prostheses were the most studied strategy, showing a trend toward reduced infection and improved limb salvage, not always significant. Ten comparative studies (1207 patients: 546 silver-coated, 661 uncoated) were meta-analyzed: pooled infection rates were 12.3% versus 14.5%, yielding an ARR of 3.95% (95% CI −1.02 to 8.91%) favoring silver coating (not significant), NNT ≈ 25. Heterogeneity was moderate ( I 2 = 23.2%). Silver-hydroxyapatite-coated total hip arthroplasty (THA) showed excellent infection prevention without loosening or toxicity. Iodine-coated implants had the strongest evidence, significantly reducing deep infection versus uncoated implants. Bacteriophage therapy was promising but limited to small case series or case reports. Other approaches, particularly based on bacteriophage therapy, showed promising results but were mainly supported by small case series or case reports. Overall, the evidence was limited by a moderate-to-critical risk-of-bias due to nonrandomized study designs and confounding by indication. Nonantibiotic antibacterial strategies, particularly implant coatings, represent promising adjuncts for reducing infection risk in high-risk orthopedic procedures, supported by a growing body of comparative clinical evidence. Bacteriophage therapy, by contrast, remains experimental, currently supported only by case reports and small case series and should not yet be regarded as an adjunct applied in routine clinical practice. Overall, current clinical evidence remains limited and heterogeneous. Well-designed prospective controlled studies are needed to clarify the effectiveness of these strategies and to define their role within contemporary infection-prevention protocols.