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Indirect evidence provides poor evidence in support of concomitant use of amoxicillin/metronidazole to improve periodontal measures

L. Virginia Powell DMD, GPR .


Systematic Review Conclusion

Systematic antimicrobial therapy using a combination of amoxicillin and metronidazole as an adjunct to scaling and root planing (SRP) can enhance the clinical benefits of non-surgical periodontal therapy in otherwise healthy teens and adults.

Critical Summary Assessment

Because there was no direct comparison with SRP alone, this review can only show that patients improve post-treatment with SRP supplemented with antibiotic therapy.

Evidence Quality Rating

Poor Evidence

Structured Abstract

Clinical Questions:

In healthy patients (teenagers and adults) with periodontitis, what is the effect of concomitant systemic administration of amoxicillin and metronidazole as an adjunct to SRP with respect to mean treatment outcome (end scores versus baseline) in terms of periodontal pocket depth (PD), clinical attachment loss (CAL), bleeding on probing (BOP), and plaque score (PI)?

Review Methods:

Review authors searched three data-bases using a well-developed search strategy for papers published through April 1, 2012. They also searched early-view and accepted papers from several dental journals and hand searched reference lists of selected studies. Eligibility criteria included: papers written in English; randomized or controlled clinical trials, cohort studies, or case series (including trials without a control group); study subjects in good health without dentures or orthodontics and with periodontitis that had not been treated for at least six months; intervention including SRP and an amoxicillin/metronidazole combination; outcome variables that included PD and CAL as primary and BOP and PI as secondary measures; minimum follow up of four weeks; and data presented by pre- and post-treatment means. Two reviewers screened papers independently with a third reviewer available to resolve disagreements. Reviewers evaluated heterogeneity and study quality. They described reasons for study exclusion. They analyzed weighted mean changes with meta-analysis.

Main Results:

The authors identified 526 titles, and they selected 27 original studies (total 525 subjects) that met a priori inclusion criteria. Eighteen studies were randomized controlled trials (RCT's), seven were cohort studies, one was a retrospective study, and one was a pilot study. Heterogeneity was significant in regard to study design, participants, and interventions. They reported that among the 27 [sic] included studies, 15 studies were at low risk of bias, five were of moderate risk, and eight were of high risk. The weighted mean difference between pre- and post-treatment with SRP plus amoxicillin and metronidazole were: PD -1.43 (confidence interval (CI) -1.47; -1.39); CAL +0.94 (CI +0.90; +0.98); PI -56% (CI -59; -53); and BOP -66% (CI -68; -64). Benefits of therapy improved from three to six months and were more dramatic for deeper pockets: PD for pockets greater than or equal to 7mm: -3.72 (CI -3.83; 3.61); CAL +2.66 (CI +2.51; +2.81). Adverse events included nausea and vomiting most frequently (n=12); only three studies reported no adverse events; 13 did not comment on adverse events.


Review authors conclude that a combination of amoxicillin and metronidazole enhances treatment effects of non-surgical SRP therapy and that this combination reduces the need for further periodontal treatment. Benefits are especially significant when treating deep periodontal pockets.

Source of Funding:

This review was self-funded by the authors, the University of Amsterdam and VU University and the University of Missouri-Kansas City.


Importance and Context:

Professional journals (1) have advocated the use of antibiotics as an adjunct to SRP therapy especially in refractory cases, (cases that did not respond to SRP alone). Since practitioners are cautioned to use antibiotics sparingly to avoid resistance and adverse events, the added benefit of antibiotics needs to be identified so that appropriate protocols may be developed.

Strengths and Weaknesses of the Systematic Review:

The clinical question does not include the critical element of comparison to SRP alone, and therefore provides little useful information to the practitioner. Claims of improvement over SRP alone are based on indirect comparisons with the literature and do not constitute acceptable evidence. The authors used a thorough and inclusive search strategy and defined a priori inclusion criteria, although they excluded non-English articles. Two reviewers determined study acceptance with a third available for disagreements, and they provided reasons for exclusion. Authors provided demographic data when available and evaluated studies for risk of bias. They acknowledged significant heterogeneity, but provided no statistical assessment; therefore the appropriateness of their method for pooling data could not be determined.

Strengths and Weaknesses of the Evidence:

Evidence included only one arm of fifteen 15 high quality RCT's, in addition to uncontrolled trials and studies of weaker design. As noted, none had comparison groups. Time frames were short; six months duration was the longest reported. Heterogeneity was significant in regard to study population, disease state, and antibiotic dosage. Adverse events were not addressed in 13 studies.

Implications for Dental Practice:

This review does not provide any evidence to answer the clinically-relevant question of whether administration of amoxicillin and metronidazole improves periodontal health over SRP alone. 1. Slots J, Members of the 2003-2004 Research, Science and Therapy Committee. Position Paper: Systemic Antibiotics in Periodontics. J Periodontol 2004; 75:1553-1565.

Critical Summary Publication Date:


These summaries are not intended to, and do not, express, imply, or summarize standards of care, but rather provide a concise reference for dentists to aid in understanding and applying evidence from the referenced systematic review in making clinically sound decisions as guided by their clinical judgment and by patient needs. American Dental Association © 2019