Is progression of periodontitis relevantly influenced by systemic antibiotics? A clinical randomized trial

Abstract

Aim: We investigated the long-term impact of adjunctive systemic antibiotics on periodontal disease progression. Periodontal therapy is frequently supplemented by systemic antibiotics, although its impact on the course of disease is still unclear.

Material & methods: This prospective, randomized, double-blind, placebo-controlled multi-centre trial comprising patients suffering from moderate to severe periodontitis evaluated the impact of rational adjunctive use of systemic amoxicillin 500 mg plus metronidazole 400 mg (3x/day, 7 days) on attachment loss. The primary outcome was the percentage of sites showing further attachment loss (PSAL) ≥1.3 mm after the 27.5 months observation period. Standardized therapy comprised mechanical debridement in conjunction with antibiotics or placebo administration, and maintenance therapy at 3 months intervals.

Results: From 506 participating patients, 406 were included in the intention to treat analysis. Median PSAL observed in placebo group was 7.8% compared to 5.3% in antibiotics group (Q25 4.7%/Q75 14.1%; Q25 3.1%/Q75 9.9%; p < 0.001 respectively).

Conclusions: Both treatments were effective in preventing disease progression. Compared to placebo, the prescription of empiric adjunctive systemic antibiotics showed a small absolute, although statistically significant, additional reduction in further attachment loss. Therapists should consider the patient's overall risk for periodontal disease when deciding for or against adjunctive antibiotics prescription.

Trial registration: ClinicalTrials.gov NCT00707369.

Keywords: amoxicillin/metronidazole; attachment loss; clinical relevance; debridement; outcome parameter; periodontitis; randomised controlled trial; systemic antibiotics.

Figure 1

Study design and flow. (a) The timeline for the trial is illustrated. After screening (visit1), baseline measurements and subsequent randomization was performed (visit 2). After dental biofilms were disrupted during initial treatment (mechanical debridement), blinded amoxicillin/metronidazole or placebo was dispensed (visit 3). Re‐evaluation (visit 4) was performed 3.5 months after visit 2. Maintenance therapy (mechanical debridement) was carried out at 3 months intervals (visits 5 through 12). Measurements were also conducted 9.5, 15.5, 21.5 and 27.5 months after visit 2 (visits 6, 8, 10 and 12). (b) Sequence of screening, randomization, drop outs, serious adverse events and follow‐up of participants are illustrated. From 506 randomized patients, 93 dropped out over the 27.5 months study period. Overall, 406 patients were included in the intention to treat analyses, but, due to incomplete medication intake, only 345 patients were included into the per‐protocol analysis.

Figure 2

Changes in main clinical parameters over the course of the study. (a) Percentage of sites with attachment loss (PSAL) ≥1.3 mm displayed for the placebo and antibiotics (amoxicillin/metronidazole) group over the course of the study. *p < 0.001, from stratified van Elteren tests. (b) The percentage of sites with pocket probing depth (PPD) ≥5 mm are displayed for the placebo and antibiotics (amoxicillin/metronidazole) group over the course of the study. At baseline (visit 2), the percentage of PPD ≥5 mm was not different in both groups (p = 0.66, stratified van Elteren test). Beginning with visit 4, although both groups achieved clinically favourable levels, the antibiotics group patients showed statistically noticeable lower presence of PPD ≥5 mm compared to placebo patients. *p < 0.001.