Systemic antimicrobials as an adjunct in the management of periodontitis - which drug is best?

Design: This study is a systematic review and meta-analysis that assesses systemic antimicrobials: azithromycin (AZT) and amoxicillin/metronidazole (AMX/MTZ), as adjuvants to subgingival instrumentation in the treatment of periodontitis. The aim is to establish if one antimicrobial is superior as an adjuvant therapy in the management of periodontal disease.

Study Selection: This systematic review and meta-analysis included randomised controlled trials (RCTs), controlled clinical trials, and prospective and retrospective human studies. Participants had to be adults (≥18 years of age) with a diagnosis of periodontitis in the categories: chronic/aggressive, stages II/III, grades B/C. All participants completed full mouth subgingival instrumentation (SI) with the use of adjunct systemic antimicrobial therapy: the intervention group: AZT and the control group: AMX/MTZ. A total of 779 studies were retrieved from the data search; following the application of selection criteria and independent review duplicated by two authors, seven studies were eligible for review. Two studies were subsequently excluded due to insufficient information. Therefore five studies were included in the review, all were self-funded and four were conducted in recognised universities.

Data Analysis: The primary outcome measure was probing pocket depth changes at 1-12 months. Secondary outcome measures were: the number of residual sites with pocket depths ≥5 mm, clinical attachment levels, bleeding on probing, plaque indices (at 1-12 months), and occurrence of adverse events. Review Manager Software (The Cochrane Collaboration, Copenhagen, Denmark) was used to conduct meta-analysis. Heterogeneity between studies was expected, therefore the random-effects model was utilised to pool results from multiple studies. Statistical heterogeneity was assessed by I2 and Cochrane's test for heterogeneity. The certainty of evidence was assessed and a summary of GRADE criteria: risk of bias, inconsistency, imprecision, indirectness and publication bias. Bias was graded for the five studies included in this meta-analysis and systematic review. Two studies were low risk, two were moderate risk and one was high risk. The study rated high for risk of bias was due to an incomplete description of blinding. Three of the studies were rated low bias for outcome measurement as they reported blinding of data assessors. No studies had deviations from the intended interventions and all outcomes were detected; therefore, all studies were rated as low bias for these domains.

Results: All five of the studies demonstrated changing in probing pocket depths at 1-3 months, however, the intervention and control cohorts showed no significant difference. One study showed a statistically significant difference in probing pocket depths at 12 months, in favour of AZT. This systematic review and meta-analysis demonstrates no statistically significant difference between the two cohorts: AZT and AMX/MTZ for mean changes in clinical attachment level, probing pocket depths or bleeding on probing at 1-3 months; when used as an adjunct to mechanical intervention in the treatment of periodontitis. It was recorded, evidence of low to moderate certainty, that for the AZT cohort: fewer adverse events were evident and fewer sites with residual probing pocket depths of ≥5 mm at 1-3 months were recorded.

Conclusions: Based on this systematic review and meta-analysis, there is no statistically significant superior drug therapy, comparing the use of AZT versus AMX/MTZ as an adjunct in the treatment of periodontists. However, evidence of low to moderate certainty demonstrates fewer adverse events and fewer sites with residual pocket depths ≥5 mm at 1-3 months in the AZT cohort, compared to the AMX/MTZ cohort. A greater number of clinical trials and a stronger evidence base in the future will allow for authentication of current findings.