Periodontitis: Adjunctive amoxicillin and metronidazole with full-mouth scaling and root planing

Scaling and root planing is a key element of the management of periodontitis. Full-mouth scaling and root planing is undertaken in 1-2 sessions within 24-48 hours with or without antiseptics. Adjunctive systemic antibiotics are sometimes applied, and reviews have suggested some additional benefit with amoxicillin and metronidazole. However, there is a lack of consensus over its use, duration and dosage .

The aim of this review was to evaluate whether amoxicillin and metronidazole (AMX/MET) as an adjunct to full-mouth scaling and root planing (FMSRP) improved clinical outcomes.

Methods

Searches were conducted in the PubMed, Embase, Cochrane Library and OpenGrey databases supplemented by hand searches of the journals, Journal of Dental Research, Journal of Periodontology, Journal of Clinical Periodontology, and Journal of Periodontal Research.

Randomised clinical trials (RCTs) comparing AMX/MET as an adjunct to FMSRP with FMSRP alone for at least 3 months were considered. Two reviewers independently selected studies, extracted data and assessed risk of bias using the Cochrane domains-based tool. The primary outcome was clinical attachment level (CAL) gain at 3 and 6 months with pocket probing depth reduction as 3 and 6 month and adverse events as secondary outcomes. Risk ratios and mean difference (MD) with 95% confidence intervals (95% CIs) were used for dichotomous and continuous data, respectively. Doses of AMX/MET of 500/250 mg, 500/375 mg, 375/500 mg, and 375/250 mg were classified as low dose, while 500/500 mg were classified as high dose. Three subgroups of drug duration 3, 7, and 10 days were assessed.

Results

11 studies involving a total of 1006 patients were included with 10 contributing to the meta-analyses.
Meta-analysis for CAL gain (7 studies) found a statistically significant improvement at 3 and 6 months
- 3 months; MD = 33mm (95%CI: 0.23 to 0.44),
- 6 months; MD = 0.37mm (95%CI: 0.22 to 0.52).
Meta-analyses found a significant improvement in CAL gain at 3 months with both higher and lower drug doses.
- high dose; MD = 0.27mm (95%CI: 0.12 to 0.42) [5 studies],
- low dose; MD = 0.36mm (95%CI: 0.07 to 0.60)[3 studies].
At 6 months a greater benefit in CAL gain was seen in the those receiving higher drug dosage with no additional benefit for those on low dosage
- high dose; MD = 0.42mm (95%CI: 0.25 to 0.59) [4 studies],
- low dose; MD = 0.25mm (95%CI:- 0.17 to 0.68) )[3 studies].
With the exception of 3-day drug duration at 3 months meta-analysis found significant CAL gain compared to control groups (see table below).

Drug durations	MD (95%CI) at 3 months	MD (95%CI) at 6 months
3 days	0.19mm (−0.05 to 0.42)	0.55mm (0.22 to 0.88)
7 days	0.28mm (0.13 to 0.42)	0.30mm (0.12 to 0.49)
10 days	0.49mm (0.32 to 0.66)	0.52mm (0.35 to 0.69)

A significant improvement in PPD was seen in the FMSRP+AMX/MET at both 3 and 6 months

3 months: MD = 0.31mm (95%CI: 0.20 to 0.42) [9 studies],
6 months: MD = 0.47mm (95%CI: 0.29 to 0.64) [7 studies].

A significant reduction in PPD was seen with both high and low doses compared to controls at 3 months.
- high dose; MD = 0.42mm (95%CI: 0.27 to 0.57),
- low dose; MD = 0.24mm (95%CI:- 0.12 to 0.36).
At 6 months a significant difference for PPD was only found for the high dose
- high dose; MD = 0.56mm (95%CI: 0.40 to 0.71).
Meta-analysis showed significant reduction in PPD compared to control groups for all drug durations at 3 and 6 months ) see table below).

Drug durations	MD (95%CI) at 3 months	MD (95%CI) at 6 months
3 days	0.35mm (0.07 to 0.63)	0.64mm (0.31 to 0.97)
7 days	0.33mm (0.12 to 0.54)	0.49mm (0.22 to 0.76)
10 days	0.30mm (0.20 to 0.40)	0.30mm (0.20 to 0.40)

162 out of 467 patients in the test group reported adverse effects compared with 140 out of409 in the control group.

Conclusions

The authors concluded: –

adjunctive use of AMX/MET to FMSRP could provide additional clinical benefits in patients with periodontitis at 3 and 6 months after treatment. FMSRP adjunctive to AMX/ MET with high dose of 500 mg/500 mg could provide a stable and significant improvement in CAL gain during both the 3-month and 6-month follow-up. However, based on the small number of included studies and limited evidence, no recommendation could be made regarding drug duration.

Comments

A Cochrane review of adjunctive antimicrobials for non-surgical periodontal treatment was published last year (Dental Elf – 23^rd Nov 2020). That extensive review included 45 RCTs concluding,

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.’

A subsequent review by Sgolastra et al (Dental Elf – 5^th May 2021) suggested that amoxicillin and metronidazole was the best adjunctive agent. However as with the Cochrane review the quality of the evidence was of low certainty. The current review has searched a good range of databases including 11 studies,5 of which were included in the Cochrane review. Only two of the 21 studies included in the Sgolastra review are included in this new review. Most of the included studies are small with only 3 studies having more than 50 patients although the authors assessed most the studies as having low risk of bias. While the findings indicate significant benefits in terms of CAL and PPD with the use of systemic AMX/MET there is a question as to whether these benefits of around 0.35 mm are clinically important particularly in light of increasing concern about the overuse of antibiotics and antimicrobial resistance.

Links

Primary Paper

Zhao H, Hu J, Zhao L. The effect of drug dose and duration of adjuvant Amoxicillin-plus-Metronidazole to full-mouth scaling and root planing in periodontitis: a systematic review and meta-analysis. Clin Oral Investig. 2021 Oct;25(10):5671-5685. doi: 10.1007/s00784-021-03869-w. Epub 2021 Mar 10. PMID: 33751238.

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