Adjunctive Systemic Antimicrobials in the Treatment of Generalized Stage III, Grade C Periodontitis: A Triple-Blind, Randomized Placebo-Controlled Trial

Abstract Objectives To evaluate the clinical efficacy of subgingival instrumentation (SI) with adjunctive systemic amoxicillin (AMX) and metronidazole (MTZ) compared with SI and placebo in young adults with generalized stage III, grade C periodontitis. Background While systemic antibiotics are often prescribed for high-grade periodontitis, the clinical relevance of their statistical benefits remains debated within current disease classification and antibiotic stewardship frameworks. Methods In this triple-blind, randomized controlled trial, 50 patients (18–35 years) received SI + AMX/MTZ (500 mg TID, 7 days) or SI + placebo. Periodontal parameters (PPD, CAL, BOP, and FMPI) were recorded at baseline, 6, and 12 months. The primary clinically relevant outcome was the therapeutic success rate (absence of pockets > 5 mm) at 12 months. Results Both groups showed significant clinical improvements at 12 months ( p < 0.001). The test group achieved statistically greater mean PPD reduction (difference: 0.53 mm; p = 0.024) and CAL gain (difference: 0.61 mm; p < 0.001). However, no statistically significant differences were observed in therapeutic success rates at 12 months (96.0% for test vs. 88.0% for control; p = 0.609), indicating that high-quality SI alone can lead to comparable clinical stability in this population. Conclusion Although adjunctive AMX + MTZ provides statistically greater mean PPD and CAL improvements, these surrogate findings do not translate into significantly higher rates of therapeutic success. The high efficacy of mechanical debridement alone suggests a “ceiling effect,” where the added clinical value of systemic antibiotics is limited. Consequently, routine use of systemic adjuncts for Stage III Grade C periodontitis is not supported by these data; their application should be carefully individualized within a strict framework of antibiotic stewardship.