Influence of Local and Systemic Antibiotics in Non-Surgical Peri-Implantitis Treatment: A Systematic Review and Meta-Analysis Update

Background: Adjunctive antibiotics are frequently used alongside mechanical debridement (MD) for peri-implantitis, yet their additional clinical benefit remains uncertain. Objective: To systematically assess whether adding local or systemic antibiotics to non-surgical MD improves clinical outcomes in peri-implantitis. Methods: The review protocol was registered in PROSPERO (CRD42022380401). We included randomised controlled trials (RCTs) involving peri-implantitis patients treated with MD plus local or systemic antibiotics, compared to MD alone, with at least 3 months of follow-up. Searches were conducted in PubMed, Cochrane Library, LILACS, Web of Science, and Embase up to 9 April 2025. Eleven RCTs (634 patients) were included in the qualitative synthesis. The Cochrane RoB 2.0 tool evaluated the risk of bias. Random-effects meta-analyses of data from 10 studies, adjusting results to an equivalent 6-month follow-up time-frame, assessed treatment efficacy based on changes in probing pocket depth (PPD) and bleeding on probing (BoP), the primary outcomes. Meta-regressions examined the influence of mean patient age and implant-to-patient ratio on adjusted outcomes. Results: Systemic antibiotics resulted in generally greater PPD reduction and BoP reduction over MD alone or plus chlorhexidine, with the greatest benefits observed in amoxicillin-based multi-agent regimens and longer follow-up duration. Comparatively, local antimicrobial adjuncts performed less effectively on PPD reduction. No implant losses were reported, and adverse events were rare. Limitations: Some included trials had a high risk of bias and considerable heterogeneity. Follow-up was limited to the short term, and definitions of clinical “success” varied across studies. Conclusions: Adjunctive systemic antibiotics, particularly amoxicillin-based combinations, substantially improve short-term clinical outcomes of non-surgical peri-implantitis treatment compared to MD alone. Nevertheless, given the variability in study quality and potential risks associated with antibiotic use, their application should be judicious. Further long-term RCTs are warranted to confirm sustained efficacy and safety.