| Summary: | Background: The aim was to compare two different systemic antibiotics regimens adjunctive to non-surgical periodontal therapy when <i>Aggregatibacter actinomycetemcomitans</i> was not detected in the subgingival biofilm. Methods: A total of 58 patients with periodontitis and with no <i>A. actinomycetemcomitans</i> in the subgingival biofilm were treated with full-mouth subgingival instrumentation and either metronidazole (MET; <i>n</i> = 29) or amoxicillin/metronidazole (AMX/MET; <i>n</i> = 29). Probing depth (PD), clinical attachment level (CAL) and bleeding on probing (BOP) were recorded at baseline, as well as after three and six months. Subgingival biofilm and gingival crevicular fluid were collected and analyzed for major periodontopathogens and biomarkers. Results: PD, CAL and BOP improved at 3 and 6 months (each <i>p</i> < 0.001 vs. baseline) with no difference between the groups. Sites with initial PD ≥ 6 mm also improved in both groups after 3 and 6 months (<i>p</i> < 0.001) with a higher reduction of PD in the AMX/MET group (<i>p</i> < 0.05). T. forsythia was lower in the AMX/MET group after 3 months (<i>p</i> < 0.05). MMP-8 and IL-1β were without significant changes and differences between the groups. Conclusion: When <i>A. actinomycetemcomitans</i> was not detected in the subgingival biofilm, the adjunctive systemic use of amoxicillin/metronidazole results in better clinical and microbiological outcomes of non-surgical periodontal therapy when the application of systemic antibiotics is scheduled.
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