Does timing of systemic antibiotics influence periodontal treatment outcomes? A randomized clinical trial

Abstract

Background

The aim of this study is to determine whether the timing of metronidazole (MTZ) and amoxicillin (AMX) administration, relative to scaling and root planing (SRP), influences the clinical and microbiological outcomes of periodontal treatment.

Methods

In this double-blind, placebo-controlled, randomized clinical trial, subjects with stage III/IV periodontitis were assigned to receive SRP over 14 days with either (1) MTZ+AMX three times a day (TID) during SRP followed by placebo (early antibiotic group) or (2) placebo during SRP followed by MTZ + AMX TID immediately after SRP (late antibiotic group). Clinical parameters (probing depth [PD], clinical attachment level [CAL], visible plaque, bleeding on probing, suppuration) were recorded at baseline, 3 months and 1 year. Subgingival biofilm samples from nine sites per subject were individually analyzed using checkerboard DNA–DNA hybridization targeting 40 bacterial species. Bacterial correlation networks were constructed using SparCC and visualized in Cytoscape based on the bacterial abundance.

Results

Sixty-eight subjects were included in the study, with 34 per group. Both groups achieved comparable clinical improvements. Approximately 60% of participants in each group reached the primary treatment endpoint at 1 year (≤ 4 sites with PD ≥ 5 mm at 1 year; p > 0.05), and the reductions in PD and CAL did not differ significantly between groups (p > 0.05). Microbiologically, the early antibiotic group demonstrated faster and more pronounced ecological reorganization, with reduced centrality of red and orange complex species and earlier integration of health-associated taxa such as Actinomyces spp. In contrast, the late group showed slower microbial restructuring, with Actinomyces taxa remaining entangled with orange-complex organisms and persistent dysbiotic clusters dominated by Fusobacterium subspecies.

Conclusions

While the timing of antibiotic administration relative to SRP did not influence the overall clinical efficacy of periodontal treatment, initiating antibiotics on the first day of mechanical debridement promoted a more rapid and beneficial restructuring of the subgingival microbial community.

Plain language summary

When treating severe gum disease, dentists often combine deep cleaning with antibiotics to help eliminate harmful bacteria. However, the best time to give these antibiotics—at the start or the end of the cleaning process—has never been tested. This study compared two approaches in 68 patients with advanced gum disease: one group received antibiotics during their cleaning sessions over 2 weeks, while the other received them immediately after cleaning finished. Both groups showed similar improvements in gum health after 1 year, with about over half achieving successful treatment outcomes. However, analyzing the bacterial communities revealed an interesting difference: patients who started antibiotics early experienced faster and more thorough changes in their mouth bacteria. Their harmful bacteria disappeared more quickly, and beneficial bacteria formed a stable, protective community sooner. In contrast, the late-antibiotic group showed slower bacterial changes, with beneficial bacteria remaining mixed with harmful ones for longer. While both timing strategies work clinically, starting antibiotics at the beginning of treatment may help to establish a healthier, more stable bacterial community in the gums, potentially offering better long-term protection against disease recurrence.