Shaping the Indications for Periodontal Adjunctive Antibiotics in dental practice: A PBRN Clinical Trial Periodontitis is a bacterial inflammatory disease that has been reported to affect nearly 40% of Americans aged 30 years or older. If left untreated, periodontitis can lead to tooth loss and patient-perceived morbidity. Historically, antibiotic use has been an integral part of periodontal disease treatment. However, antibiotic stewardship calls for rationalizing their prescription to reduce antibiotic misuse and development of resistant strains. Across medical disciplines, there is a clear direction to identify individuals who in fact may benefit from antibiotic use and to provide guidelines for their use. As of 2018, the American Dental Association has developed evidence-based guidelines limiting circumstances for prophylactic antibiotic use in dental practice; however, no national guidelines exist for antibiotic use in treatment of periodontal infections because of lack of adequately powered trials assessing disease- and person-specific indications. Thus, dentists are left to decide when adjunctive antibiotics are indicated, and which dental patients need them to achieve periodontal health. In the context of periodontitis treatment, a biological rationale exists to support adjunctive antibiotic use against periodontal pathogenic bacteria, but clinical results of their use have presented conflicting results. Currently, very limited documentation of the prescription patterns and utilization of antibiotics as periodontal treatment adjuncts among US practitioners exist. Nonetheless, data from academic studies suggest that adjunctive systemic antibiotics may only be beneficial for certain populations, as the biological response to treatment is highly variable across individuals. This marked variability warrants the identification of person- and/or disease-related characteristics that are linked to maximum benefit from adjunctive antibiotic treatment. Consequently, clear guidelines can then be established for tailored indications for their use with the ultimate goal of minimizing antibiotic misuse in periodontal treatment to avoid development of antibiotic resistance. The objective of this study is to assess the effectiveness of adjunctive Amoxicillin/Metronidazole combination antibiotics to non-surgical periodontal therapy in clinical practices within the National Dental PBRN by conducting the largest randomized clinical trial (RCT) of adjunctive antibiotics. Further, within this PBRN study, current decision-making factors for adjunctive antibiotic prescription will be surveyed to assess the state of affairs in clinical practice. Importantly, leveraging the well-powered RCT dataset, high responders to adjunctive antibiotic treatment will be identified and the predictive validity of decision-making factors currently employed by clinicians will be assessed to develop clear indications for prescription. Collectively, results of adjunctive antibiotic...