Systemic Antibiotics as Adjuncts in Periodontal Therapy for Stage III and Stage IV Periodontitis: An Umbrella Review Aligned with the 2018 World Workshop Classification, with AMSTAR-2 Critical Appraisal

Introduction: Severe periodontitis, corresponding to Stage III and Stage IV disease according to the 2018 World Workshop classification, represents a substantial global health burden. Systemic antibiotics have been investigated as adjuncts to mechanical periodontal therapy; however, their effectiveness and appropriate use in severe periodontitis remain uncertain. This umbrella review aimed to synthesize the available evidence on adjunctive systemic antibiotics in Stage III and Stage IV periodontitis and assess the methodological quality of the available systematic reviews. Methods: This umbrella review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A systematic search of MEDLINE, Embase, and other relevant databases was conducted from June 2018 to June 2026. Systematic reviews evaluating adjunctive systemic antibiotics in patients with Stage III or Stage IV periodontitis, classified according to the 2018 World Workshop, were eligible. Methodological quality was assessed using AMSTAR-2 and overlap among primary studies was evaluated using the Corrected Covered Area (CCA). Results: Two systematic reviews met the inclusion criteria: a network meta-analysis by Lin et al. and a systematic review by Jones and Hoyle focusing on azithromycin. The CCA was approximately 52.9%, indicating substantial overlap between the included reviews. Lin et al. reported moderate-certainty evidence that adjunctive amoxicillin plus metronidazole (AMX + MTZ) resulted in greater clinical attachment level gain and probing pocket depth reduction compared with mechanical debridement alone. Jones and Hoyle found insufficient evidence to support routine adjunctive azithromycin, owing to low certainty and heterogeneity among studies. Discussion and Conclusions: Adjunctive systemic antibiotics, particularly AMX + MTZ, may provide additional clinical benefits in severe periodontitis. However, the limited number of systematic reviews, substantial overlaps, and uncertainty surrounding some antibiotic protocols limit the strength of the evidence. Current findings support selective rather than routine antibiotic use, guided by individual patient and disease characteristics and antimicrobial stewardship. Future studies should emphasize long-term outcomes and consistently distinguish Stage III from Stage IV periodontitis.