Non-surgical periodontal therapy – which antibiotic regime?

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Periodontal disease is very common and non-surgical treatment in the form of scaling and root planing plays an important role in its management. Adjunctive antibiotics have been recommended to improve outcomes and a large number of reviews has demonstrated a small additional benefit. While a range of antimicrobial agents have been used there is some evidence to suggest that a combination of amoxicillin and metronidazole may be an effective combination.

The aim of this review was to determine the optimum dose and duration of amoxicillin-plus-metronidazole prescribed as an adjunct to non-surgical treatment of periodontitis.


Searches were conducted in the Medline, Embase, Cochrane Central Register of Controlled Trials and the WHO International Clinical Trials Registry Platform databases. Only blinded, placebo-controlled, randomised clinical trials (RCTs) with a minimum of 3 months follow up published in English or French were considered.  The primary outcomes measures were pocket probing depth (PPD) and Clinical Attachment level (CAL) 3 months after completion of non-surgical treatment.

Two reviewers independently selected studies and abstracted data. Risk of bias was assessed using the Cochrane tool.  main summary measure was a weighted mean difference in PPD and CAL at 3 months. Meta-analysis was undertaken using the inverse-variance method and a random-effects model.


  • 18 RCTs met the inclusion criteria.
  • 8 were considered to be at low risk of bias, 7 at unclear risk and 3 at high risk.
  • 15 studies contributed to the meta-analysis at 3 months a small additional benefit in favour of adjunctive use of amoxicillin & metronidazole was found for PPD and CAL
    • PPD ; MD=  -0.36mm (95%CI; -0.43 to  -0.29)
    • CAL ;  MD=  -0.29mm (95%CI; -0.39 to -0.19)
  • 287 adverse events were recorded in the antibiotic groups (636 patients) compared with 157 in the placebo group (287 patients)


The authors concluded: –

There was no clinically meaningful difference between different doses or duration of amoxicillin-plus-metronidazole at 3 months post-treatment. Without compelling evidence to suggest that any one regimen performed superiorly, principles of responsible antibiotic use generally recommend the highest dose for the shortest duration of time to reduce the risk of antibiotic resistance. Therefore, a 7-day regimen of 500/500 mg or 500/400 mg of amoxicillin and metronidazole would be most appropriate.


A number of major databases have been searched for this review although restricting inclusion to two languages may have resulted in some exclusions. Most of the included studies have small sample sizes with 11 studies including less than 40 patients. There was also a variation in antibiotic dose. Overall this review demonstrates a small additional benefit with the adjunctive use of antibiotics but little or no additional benefit with the use of higher dosage or longer courses of antibiotics.

The authors indicate that there is no clinically meaningful difference in outcomes at 3 months between various dosages on antibiotics so recommend shorter higher dosages of antibiotics are used. While antibiotics do produce small additional benefits when used as adjuncts there is the question as to whether these are clinically important. Given the growing threat of antibiotic resistance the question then arises, should we be using them at all for the management of periodontal disease, or at the very least only using them on a small minority of patients


Primary Paper

McGowan K, McGowan T, Ivanovski S. Optimal dose and duration of amoxicillin-plus-metronidazole as an adjunct to non-surgical periodontal therapy: A systematic review and meta-analysis of randomized, placebo-controlled trials. J Clin Periodontol. 2018 Jan;45(1):56-67. doi: 10.1111/jcpe.12830. Epub 2017 Nov 21. Review. PubMed PMID: 29027242.

Other references

Original review protocol on PROSPERO


Dental Elf – 7th Mar 2016

Amoxicillin and metronidazole as an adjunct to scaling and root planning for periodontitis?





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