Antimicrobial Resistance in Periodontal Disease: Rethinking Adjunctive Therapy in the Metagenomics Era, the Pressing Need for Precision Treatment and Periodontal Resistome Mapping

ABSTRACT Systemic antibiotics are effective when used as adjunctive therapy in the treatment of periodontitis; however, their use must be balanced against antimicrobial resistance, which is a major threat to global public health. This review provides an expert synthesis of the literature and a field‐level overview of antimicrobial resistance in periodontal therapy, highlighting current knowledge and emerging directions, while examining how adjunctive antibiotic protocols may contribute to resistance within the periodontal microbiome through emerging metagenomic insights. To provide this synthesis, the PubMed database was searched for English‐language publications using combinations of the terms periodontitis, systemic antibiotics, antimicrobials, resistance, resistome, therapeutic adjuncts, resistance genes, susceptibility, antibacterial and drug resistance, and the findings are presented as a narrative review. The evidence indicates that a substantial proportion of patients with periodontitis harbour subgingival microbiota that are non‐susceptible to at least one antibiotic used in periodontal therapy. Across the included studies, antimicrobial resistance was most frequently reported in Prevotella and Porphyromonas species, while some studies also identified virulence‐associated factors in Staphylococcus aureus , a non‐classical periodontal organism detected within the subgingival microbiota. Overall, current evidence indicates a high prevalence of antibiotic resistance genes in the subgingival microbiota of patients with periodontitis and highlights the ecological consequences of adjunctive antibiotic use. These findings reinforce the need to optimize antibiotic prescribing protocols within an antibiotic stewardship framework and support further metagenomic investigations to refine understanding of resistance patterns, gene‐transfer mechanisms and microbiome disruption, with the aim of advancing precision‐based periodontal care.