Differential Benefits of Amoxicillin-Metronidazole in Different Phases of Periodontal Therapy in a Randomized Controlled Crossover Clinical Trial

Background: The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. Methods: This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. Results: A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P < 0.01). Twenty patients treated with antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 +/- 5.2; group B: 2.2 +/- 5.0) was not significantly different and was sustained over 12 months in both groups. Conclusion: Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.