No evidence to support benefit of 14-day courses of amoxicillin-plus-metronidazole as adjunct to non-surgical periodontal treatment at three months.

Data sources Databases including Embase, MEDLINE, The Cochrane Central Register of Controlled Trials and the WHO International Clinical Trial Register Platform were screened by two reviewers. A manual search has been performed in references from included articles and relevant reviews.Study selection Blinded, placebo-controlled, randomised clinical trials (RCTs) with a minimum follow-up of three months were included. Primary outcomes were periodontal pocket depth (PD) and clinical attachment level (CAL) changes after non-surgical periodontal treatment with adjunctive use of amoxicillin/metronidazole vs placebo in periodontitis patients. Secondary outcomes were adverse events and compliance.Data extraction and synthesis Data were extracted and compiled in a spreadsheet. Studies were grouped according to duration (seven days or fourteen days) and dose of amoxicillin/metronidazole regimen (lower dose (mg): 250/200, 375/250, 375/500, 500/250 and higher dose (mg): 500/400, 500/500). Meta-analyses were performed using inverse-variance method. Random-effect models were applied and weighted mean differences were estimated for PD reduction and CAL changes at three months. Risk of bias was assessed using the Cochrane Collaboration tool.Results Eighteen studies were identified and included in the systematic review. Among them, 15 were pooled for meta-analysis. The use of a wide range of antibiotics concentrations (amoxicillin (from 250 to 500 mg) and metronidazole (from 200 to 500 mg)) was reported and the duration of antibiotic administration ranged from three to 14 days. Eleven studies were performed in chronic periodontitis patients and six in aggressive periodontitis patients. No significant differences were found regarding mean PD and mean CAL changes according to the duration or dose of administered antibiotics (Table 1). Risk differences for adverse events in the higher dose and longer duration groups were minimally greater (0.04 and 0.05 respectively).Conclusions Longer courses (14 days) of antibiotics adjuvant to non-surgical therapy do not appear to provide better results in terms of PD reduction or CAL gain at three months. No differences were found between high and low dose groups. In this context, 400/500 mg or 500/500 mg of amoxicillin/metronidazole three times per day should be recommended for seven days.