Periodontitis is a microbially associated, host-mediated inflammation that results in loss of periodontal attachment. It is very common with the US Centers for Disease Control and Prevention (CDC) estimating that 47.2% of adults aged 30 years have some form of periodontitis and that prevalence increases with age. Non-surgical periodontal treatment or scaling and root planing (SRP) is the mainstay of treatment by a number of systemic and locally delivered antimicrobials have been used as adjuncts.
The aim of this systematic review is to assess the efficacy of clarithromycin delivered as an adjunct to non-surgical periodontal therapy locally or systemically in patients with periodontitis compared to placebo.
Searches were conducted in the PubMed, Cochrane Central Register of Controlled Trials, Embase, Web of Science and OpenGrey databases. English language randomised controlled trials (RCTs) with a minimum of 3 months follow up comparing subgingival debridement and adjunctive clarithromycin (systemic or local) against subgingival debridement and adjunctive placebo. The main outcomes were pocket probing depth (PD) and clinical attachment level (CAL). Two reviewers independently screened and selected studies with data being extracted by one reviewer and verified by a second. Rick of bias was assessed using the Cochrane domains-based approach. Data was pooled using mean differences (MD) at 3 and 6 monthly time periods. Overall certainty of evidence was assessed using GRADE.
- 7 RCTs involving a total of 352 patients were included.
- 4 studies evaluated systemic delivery of clarithromycin and 3 local delivery.
- One study was considered to be at low risk of bias and 6 at uncertain risk.
Systemic administration (4 studies, 143 patients)
|PPD reduction(95%CI)||CAL gain(95%CI)|
|3 months||0.65 mm (0.04 to 1.26 mm)||0.41 mm (−0.11 to 0.92) mm)|
|6 months||0.28 mm (−0.25 to 0.80 mm)||0.16 mm (−0.37 to 0.70) mm)|
- 2 studies reported adverse events including gastrointestinal discomfort and unpalatable taste.
- Certainty of evidence for systemically delivered clarithromycin was assessed as low
Local administration (3 studies, 209 patients)
|PPD reduction(95%CI)||CAL gain(95%CI)|
|3 months||1.01 mm (0.87 to 1.15 mm)||0.56 mm (0.44 to 0.68 mm)|
|6 months||1.20 mm (0.76 to 1.64 mm)||0.83 mm (0.64 to 1.03 mm)|
- Certainty of evidence for locally delivered clarithromycin was assessed as moderate.
The authors concluded: –
The use of locally delivered clarithromycin significantly improves treatment outcomes.
We have recently reported on three broader reviews on adjunctive antimicrobials in periodontitis patients (Dental Elf – 5th May 2021, Dental Elf – 25th Nov 2020, Dental Elf – 23rd Nov 2020). The Cochrane review by Khattri et al (Dental Elf – 5th May 2021) looked at systemic use including 3 studies of clarithromycin although only one of these was common with the current review.
This review focuses on the adjunctive use of clarithromycin locally or systemically in patients undergoing non-surgical periodontal therapy. A review protocol was registered in the PROSPERO database and follows PRISMA guidelines. A good range of databases was searched although limitation to English may have excluded some studies. Only one of the included studies was considered to be at low risk of bias in all the domains and only a small number of small studies were included. The certainty of evidence for systemically delivered clarithromycin was assessed as low and medium for locally delivered clarithromycin. While this new review suggests that the findings a statistically significant it is possible that they are not clinically important. While it has been suggested that a CAL improvement of >0.2 – 0.4mm could be considered to be a small benefit the Cochrane reviewers suggest that 1.0mm should be a ‘minimally important clinical difference’ for CAL and PD and there needs to be wider discussion and agreement about this.
Bashir NZ, Sharma P. Clarithromycin as an adjunct to periodontal therapy: a systematic review and meta-analysis. Int J Dent Hyg. 2021 Mar 26. doi: 10.1111/idh.12498. Epub ahead of print. PMID: 33773046.
Dental Elf – 5th May 2021
Dental Elf – 25th Nov 2020
Dental Elf – 23rd Nov 2020