Amoxicillin & metronidazole-adjunct to scaling & root planning?

Periodontal disease is a common if not the most common chronic inflammatory disease of man. In some population groups it is present in more than 60% with an estimate 5-20% having sever periodontitis. Scaling and root planing (SRP) plays a key role in its management and a range of adjunctive antibiotic regimes have been recommended.

This review set out to address the questions; In patients with periodontitis what is the effect of concomitant systemic administration of amoxicillin (amx) and metronidazole (met) as an adjunct to SRP compared to SRP alone with respect to mean treatment outcome ? and is the administration of antibiotics associates with side effects?

Methods

Searches were conducted in the Medline, Embase and Cochrane- CENTRAL databases. Randomised controlled trials (RCTs) or Controlled clinical trials (CCTs) were considered. Two reviewers independently screened studies, assessed study quality and abstracted data. Methodological study quality was assessed according Dutch Cochrane Centre RCT checklist. The overall body of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system.

Results

20 unique RCT studies were included.
12 were considered to be at low risk of bias, 4 medium risk and 4 at high risk.
Meta-analysis showed that SRP + amx + met provided significantly better effects overall and more pronounced PD reduction in periodontal pockets initially measuring ≥6 mm (DiffM:-0.86 mm, p < 0.00001) and gain in CAL(DiffM:+0.75 mm, p = 0.0001).

	Difference in means between groups (in mm)	95% Confidence intervals
Mean PD, Short term (2–3 months)	−0.49	(−0.60; −0.33)
Mean PD, Medium term (6 months)	−0.41	(−0.57; −0.24)
Mean PD, Long term (12 months)	−0.54	(−0.75; −0.34)
Mean PD – All 2–12 months	−0.47	(−0.58; −0.37)
PD ≥6 mm 6–12 months	−0.86	(−1.07; −0.65)
Mean CAL	+0.33	(0.23; 0.43)
CAL ≥6 mm	+0.75	(0.40; 1.09)

The meta-analysis for the secondary inflammatory parameter BOP showed that SRP + amx + met provided full mouth significantly greater reduction in BOP than SRP alone (DiffM:-6.98 %, p = 0.0001).

Conclusions

The authors concluded

despite the caveats concerning the heterogeneity of experimental designs there is moderate to strong evidence that SRP + amx + met shows significantly superior clinical outcomes in terms of PD and CAL (especially in initially deep pockets; ≥6 mm) compared to SRP alone. Therefore it would seem correct to state that these agents are important allies in the treatment of periodontal infections. SRP + amx + met might therefore reduce the need for additional periodontal therapy which would assumedly be of a surgical nature in many cases. No major adverse events associated with the intake of amx +met were reported.

Comment

This is the latest review in a long line of systematic reviews of the adjunctive use of antibiotics in treatment of periodontitis. A quick Medline search identified 24 reviews related to amoxicillin and metronidazole alone between 1997 and 2016. This review has been well conducted and an extensive appendix supports the main document.As the authors note the review is generally in line with other reviews on the topic and it suggests an additional benefit over and above SRP alone when using adjunctive amoxicillin and metronidazole. It also suggests a greater benefit in more advanced disease.

An important question is whether the small additional benefit is worth the use of antibiotics. We are all aware of the possibilities of side effects and the growing problem of antibiotic resistance. The authors raise both of these issues in the discussion noting the and recorded side effects were small and the impact on bacterial resistance from periodontal prescribing on antibiotics is likely to be small although the true impact is unknown.

The other issue to consider is the quality of the original studies. Overall 775 patients were randomised in the 20 studies and the study sample sizes ranged from 16-82. Typically periodontal studies report mean data rather than individual data and the potential impact of clustering is not as yet taken into consideration routinely in this studies which could impact both on the findings of the original studies and the reviews findings.