Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis: a Cochrane review

BACKGROUND Systemic antimicrobials can be used as an adjunct to mechanical debridement (scaling and root planing, SRP) as a non-surgical treatment approach to manage periodontitis. A range of antibiotics with different dosage and combinations are documented in the literature. The review follows the previous classification of periodontitis as all included studies used this classification. OBJECTIVES To assess the effects of systemic antimicrobials as an adjunct to SRP for the non-surgical treatment of patients with periodontitis. SEARCH METHODS Cochrane Oral Health's Information Specialist searched the fol- lowing databases to 9 March 2020: Cochrane Oral Health's Trials Register, CENTRAL, MEDLINE, and Embase. The US National Institutes of Health Ongoing Trials Register ClinicalTrials.gov and the World Health Organization International Clinical Trials Registry Platform were searched for ongoing trials. SELECTION CRITERIA AND OUTCOMES We included randomized controlled trials (RCTs) which involved individuals with clinically diagnosed untreated periodontitis. Trials compared SRP with systemic antibiotics versus SRP alone/placebo, or with other systemic antibiotics. The outcomes were: percentage of closed pockets; loss of clinical attachment level (CAL); periodontal depth (PD) and percentage of bleeding on probing (BOP). MAIN RESULTS We included 45 trials conducted worldwide involving 2664 adult participants. 14 studies were at low, 8 at high, and the remaining 23 at unclear overall risk of bias. Seven trials did not contribute data to the analysis. We assessed the certainty of the evidence for the 10 comparisons, which reported long-term follow-up (>= 1 year). None of the studies reported data on antimicrobial resistance and patient reported quality of life changes. Amoxicillin + metronidazole + SRP versus SRP in chronic/aggressive periodontitis: only the results for closed pockets and BOP showed a minimally important clinical difference (MICD) favouring amoxicillin + metronidazole + SRP (very low-certainty). Metronidazole + SRP versus SRP in chronic/aggressive periodontitis: only the results for CAL and PD showed an MICD favouring the MTZ + SRP group (very low-certainty). Azithromycin + SRP versus SRP for chronic/aggressive periodontitis: we found no evidence of a difference in percentage of closed pockets, CAL percentage of BOP (very low-certainty). Most trials testing amoxicillin, metronidazole, and azithromycin reported adverse events such as nausea, vomiting, diarrhoea, mild gastrointestinal disturbances, and metallic taste. No serious adverse events were reported. AUTHORS' CONCLUSIONS There is very low-certainty evidence (for long-term follow-up) to inform clinicians and patients if adjunctive systemic anti-microbials are of any help for the non-surgical treatment of peri- odontitis. There is insufficient evidence to decide whether some antibiotics are better than others when used alongside SRP. None of the trials reported serious adverse events but patients should be made aware of the common adverse events related to these drugs. Well-planned RCTs need to be conducted clearly defining the minimally important clinical difference for the outcomes closed pockets, CAL, PD, and BOP.