The aim of this systematic review was to compare the combination of amoxicillin and metronidazole or azithromycin when used as adjunct systemic antibiotics during the non-surgical periodontal therapy of chronic periodontitis. The databases Medline, Embase, Cochrane and Biosis were electronically searched. Additionally, a hand search was conducted up to 24 October 2019. From 76 papers, only two papers could be included in the analysis. The calculated mean probability of having probing depth (PD) <= 3 mm after non-surgical periodontal therapy in moderate (4–6 mm) and deep (> 6 mm) pockets accounted for 7% and 6% for the combination of amoxicillin and metronidazole. For azithromycin it was 3% and 1%, respectively. The mean probability of persisting pockets >= 5 mm was 0 for moderate pockets with both antibiotic therapies whereas for deep pockets therapy with amoxicillin and metronidazole seems slightly lower. On the basis of two studies included in this systematic review, azithromycin as an adjunct to scaling and root planing in the non-surgical adjunctive treatment of chronic periodontitis seems to provide clinical results similar to the combination of amoxicillin and metronidazole. On behalf of patients’ compliance and well-being, the use of azithromycin as an adjunct to non-surgical periodontal therapy of chronic periodontitis may be a substitute to amoxicillin and metronidazole. However, interpretation should be taken with caution, since the results are based on two studies only; thus, further clinical trials are necessary to underline or refute this trend.

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