Background: It has been suggested that use of systemic antibiotics should be limited to patients with specific microbiologic profiles. The main purpose of the present analysis was to study whether microbiologic testing before therapy was of value in predicting which patients would specifically benefit from adjunctive amoxicillin and metronidazole, given in the context of full‐mouth scaling and root planing (SRP) within 48 hours.Methods: This was a 6‐month, single‐center, double‐masked, placebo‐controlled, randomized longitudinal study. Fifty‐one patients received full‐mouth periodontal debridement, performed within 48 hours; then, 25 subjects received metronidazole, 500 mg, and amoxicillin, 375 mg, three times a day for 7 days, and 26 received a placebo (control group). Pooled microbiologic samples were taken from the deepest pocket at baseline in each quadrant before and 6 months after treatment. Six periodontal pathogens were quantified by real‐time polymerase chain reaction.Results: Forty‐seven patients were followed for 6 months. After treatment, test subjects had a substantially lower mean number of persisting sites with probing depth >4 mm and bleeding on probing than did control subjects (0.4 versus 3.0; P = 0.005; month 6). Aggregatibacter actinomycetemcomitans (previously Actinobacillus actinomycetemcomitans) could not be detected in the antibiotic group after treatment. However, in the placebo group, three of six subjects positive for A. actinomycetemcomitans continued to be positive. Lower frequencies were also noted in the test group for Porphyromonas gingivalis (P = 0.013) and Tannerella forsythia (previously T. forsythensis) (P = 0.007). However, even subjects testing negative for A. actinomycetemcomitans at baseline had a significantly better primary clinical outcome if they received the active drugs. The presence of six putative periodontal pathogens (A. actinomycetemcomitans, Fusobacterium nucleatum spp., P. gingivalis, Prevotella intermedia, Treponema denticola, and T. forsythia) quantified prior to therapy was not correlated with the outcome of full‐mouth SRP with or without amoxicillin and metronidazole.Conclusion: Excellent clinical results in the antibiotics group were obtained regardless of the presence or absence of six classic periodontal periopathogens prior to treatment.

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