Azithromycin as an adjunct in non-surgical periodontal therapy

As is often the case it is not unusual to find two systematic review covering the same or similar topics published by different groups around the same time. The aim of this review was to perform a meta-analysis of randomized controlled clinical trials on the efficacy of azithromycin (AZM) when used as an adjunct to scaling and root planing (SRP) on reducing probing depth, bleeding on probing (BOP) and improving attachment level (AL) in chronic periodontitis.

Methods

Searches were conducted in the Medline, Embase and Cochrane Central Register of Controlled trials with no language restrictions. Randomised controlled trials (RCTs) in adult patients with chronic periodontitis that compared azithromycin plus SRP vs. SRP alone were considered. Two reviewers independently selected studies, abstracted data and assessed study quality using a modified version of the Jadad scale with studies score 0-3 points being considered low quality and those scoring 4-7, high quality. Meta-analysis was carried out to assess he overall effect sizes of azithromycin on probing depth, attachment level (AL) and bleeding on probing (BOP).

Results

14 studies involving a total of 571 patients were included.
9 studies had a Jadad score of 4 or more.
5 trials (260 patients) compared local delivery of AZM plus SRP verses SRP alone.
9 trials (311 patients) compared systemic administration of AZM plus SRP vs. SRP alone.
Locally delivered azithromycin plus SRP statistically significantly reduced probing depth by 0.99 mm (95% CI; 0.42 – 1.57) and increased AL by 1.12 mm (95% CI; 0.31- 1.92).
Systemically administered azithromycin plus SRP statistically significantly reduced probing depth by 0.21 mm (95% CI; 0.12 – 0.29), BOP by 4.50% (95% CI; 1.45-7.56) and increased AL by 0.23 mm (95% CI; 0.07 – 0.39).

Conclusions

The authors concluded:

This meta-analysis of randomised controlled clinical trials provides evidence that both local and systemic utilization of azithromycin significantly enhances the therapeutic effectiveness of SRP in the management of chronic periodontitis. Large-scale, well-designed randomized controlled trials are needed to confirm the effect of azithromycin, as an adjunct to SRP for the treatment of chronic periodontitis, in particular among special groups, such as patients with diabetes and cigarette smokers.

Comments

Yesterday we looked another systematic review (Buset et al- Dental Elf 22^nd Sept 2015) that considered the effectiveness of AZM as an adjunct to SRP for patients with periodontitis. The review under consideration today has chosen to look a both local and systemic use of AZM for patients with chronic periodontitis whereas yesterdays review only considered systemic use but included studies that considered patients with both aggressive and chronic periodontitis. This change in acceptance criteria partially explains the difference in included studies in the two reviews. However, the review by Zhang et al has included two additional trials of systemic AZM use in patients with chronic periodontitis. In addition Zhang et al have chosen to conduct a meta-analysis for both systemic and local AZM use. Buset et al chose not to run a meta-analysis as they considered the trials to be too heterogeneous and the overall effect sizes found by Zhang et al also demonstrate high levels of heterogeneity although sensitivity analyses were conducted resulting in significant improvement in heterogeneity with limited effect on the overall effect sizes seen.

While the effect sizes are statistically important there is the question as to whether they are big enough to be clinically important in view of the potential adverse effects and risk of increasing antibiotic resistance. The available studies only include a relatively small number of patients averaging around 40 patients per study (range 20-80) so the authors call for large scale well designed RCTs would help clarify important questions around the use of AZM.