Periodontitis is a very common chronic oral health condition. It is multifactorial in origin being characterised by microbially associated, host-mediated inflammation that results in loss of periodontal attachment. The mainstay of non-surgical periodontal treatment is scaling and root planing (SRP) which aims to eliminate local irritating factors. However, as SRP does not eliminate all pathogenic bacteria systemic antibiotics have been used as an adjunct.
The aim of this Cochrane review was to assess the effects of systemic antimicrobials as an adjunct to SRP for the non-surgical treatment of patients with periodontitis.
Searches were conducted in the Cochrane Oral Health’s Trials Register, Cochrane CENTRAL, MEDLINE, Embase. The US National Institutes of Health Ongoing Trials Register (ClinicalTrials.gov) and the World Health Organization International Clinical Trials Registry databases. Randomized controlled trials (RCTs) evaluating any systematically delivered antimicrobial as an adjunct to non-surgical periodontal treatment were considered. Quasi-RCTs, cross-over, and split-mouth trials were excluded.
Pairs of reviewers independently screened and selected studies, extracted data and assessed risk of bias. The main outcome was the percentage of closed pockets (< 4 mm non bleedings site). Secondary outcomes included, clinical/relative attachment level (CAL), probing pocket depth (PD), percentage of bleeding on probing (BOP), antimicrobial resistance, adverse effects of antibiotics, long-term stability of CAL and PD and patient reported quality of life. For continuous data mead differences (MD) and 95% confidence intervals (CI) were estimated with certainty of the evidence being assessed using GRADE. A ‘minimally important clinical difference’ (MICD) was considered to be 5% for closed pockets and BOP and 1mm for CAL and PD.
- 45 RCTs involving at total of 2664 patients were included.
- 14 studies were considered to be at low risk of bias, 23 at unclear risk and 8 at high risk.
- 7 studies did not contribute to the meta-analysis.
- A MICD was not identified in most of the comparisons (see table) and evidence was of 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.
|Intervention||Outcome||No. of Studies (patients)||Mean Difference (95%CI)|
|Amoxicillin + metronidazole + SRP versus SRP in chronic/aggressive periodontitis||Closed pockets||1 (44)||-16.20% ( -25.87 to -6.53)*|
|CAL||2 (389)||-0.47 mm (-0.90 to -0.05)|
|PD||2 (389)||-0.30 mm ( -0.42 to -0.18)|
|BOP||2 (389)||-8.06% (-14.26 to -1.85) *|
|Metronidazole + SRP versus SRP in chronic/aggressive periodontitis||Closed pockets||1 (22)||-12.20% (-29.23 to 4.83)|
|CAL||3 (71)||-1.12 mm (-2.24 to 0)*|
|PD||2 (47)||-1.11 mm (-2.84 to 0.61)*|
|BOP||1 (22)||-6.90% (-22.10 to 8.30)|
|Azithromycin + SRP versus SRP for chronic/aggressive periodontitis||Closed pockets||1 (40)||2.50% (-10.19 to 15.19)|
|CAL||2 (110)||-0.59 mm (-1.27 to 0.08)|
|PD||2 (110)||-0.77 mm (-2.33 to 0.79)|
|BOP||2 (110)||1.28% (-4.32 to 1.76)|
|Amoxicillin + clavulanate + SRP versus SRP for chronic periodontitis||CAL||1 (21)||0.10 mm (-0.51 to 0.71)|
|PD||1 (21)||0.10 mm (-0.17 to 0.37)|
|BOP||1 (21)||0% (-0.09 to 0.09)|
|Doxycycline + SRP versus SRP in aggressive periodontitis||CAL||1 (22)||-0.80 mm (-1.49 to -0.11)|
|PD||1 (22)||-1.00 mm (-1.78 to -0.22)|
|Tetracycline + SRP versus SRP for aggressive periodontitis||CAL||1 (26)||-2.30 mm (-2.50 to -2.10)|
|Clindamycin + SRP versus SRP in aggressive periodontitis||CAL||1 (21)||-1.70 mm (-2.40 to -1.00)|
|PD||1 (21)||-1.80 mm (-2.47 to -1.13)|
|Doxycycline + SRP versus metronidazole + SRP for aggressive periodontitis||CAL||1 (27)||1.10 mm (0.36 to 1.84)|
|PD||1 (27)||1.00 mm (0.30 to 1.70)|
|Clindamycin + SRP versus metronidazole + SRP for aggressive periodontitis||CAL||1 (26)||0.20 mm (-0.55 to 0.95)|
|PD||1 (26)||0.20 mm (-0.38 to 0.78)|
|Clindamycin + SRP versus doxycycline + SRP for aggressive periodontitis||CAL||1 (23)||-0.90 mm (-1.62 to -0.18)|
|PD||1 (23)||-0.80 mm (-1.58 to -0.02)|
* MICD (minimally important clinical difference)
The authors concluded: –
There is very low-certainty evidence (for long-term follow-up) to inform clinicians and patients if adjunctive systemic antimicrobials are of any help for the non-surgical treatment of periodontitis. 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.
This extensive review of adjunctive systemic antibiotics as an adjunct to SRP for the non-surgical periodontal treatment was undertaken by Cochrane and follow their usual methodological approaches. Although a revised classification of periodontal disease has recently been published this review uses the earlier classification as this is used by all the included studies. Consequently, the distinction between aggressive and chronic periodontitis is maintained. The included studies were conducted in 15 different countries.
The findings from 10 other systematic review on this topic published between 2014 and 2020 are also brought into the discussion section of the review. One of these systematic reviews (Teughels et al 2020) conducted as a contribution to recent clinical guidelines for periodontal treatment included fewer studies (28) than this Cochrane review concluding “adjunctive use of systemic antimicrobials in periodontal therapy results in statistically significant benefits in clinical outcomes, with more frequent adverse events in test groups using systemic antimicrobials.“ This appears to be a more optimistic reading of the available evidence than the Cochrane Groups conclusion, which is based on a larger number of studies which they have classified as of very low certainty. The Cochrane reviewers have suggested a minimally important clinical difference for their outcomes measures and it would be useful to have these more widely discussed and agreed.
Khattri S, Kumbargere Nagraj S, Arora A, Eachempati P, Kusum CK, Bhat KG, Johnson TM, Lodi G. Adjunctive systemic antimicrobials for the non-surgical treatment of periodontitis. Cochrane Database of Systematic Reviews 2020, Issue 11. Art. No.: CD012568. DOI: 10.1002/14651858.CD012568.pub2.
Teughels W, Feres M, Oud V, Martín C, Matesanz P, Herrera D. Adjunctive effect of systemic antimicrobials in periodontitis therapy: A systematic review and meta-analysis. J Clin Periodontol. 2020 Jul;47 Suppl 22:257-281. doi: 10.1111/jcpe.13264. PMID: 31994207.
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