Targeting Bacterial Infections in Periodontal Disease: From Conventional Antibiotics to Next-Generation Therapeutics

Periodontitis is a highly prevalent chronic inflammatory disease with significant oral and systemic consequences, including associations with cardiovascular disease, diabetes, and adverse pregnancy outcomes. Although mechanical debridement remains the cornerstone of therapy, adjunctive antibiotic use is increasingly limited by antimicrobial resistance, biofilm-associated tolerance, pharmacokinetic constraints, and disruption of the commensal microbiome, leading to inconsistent outcomes and disease recurrence. This review highlights the mechanistic limitations of conventional antibiotic therapies in periodontitis and critically examines emerging next-generation therapeutic strategies aimed at overcoming these challenges. Specifically, it explores antimicrobial peptides, quorum sensing inhibitors, nanotechnology-based drug delivery systems, host modulation approaches, and microbiome-targeted therapies, with emphasis on their molecular mechanisms, clinical relevance, and translational potential. By integrating microbial, host, and pharmacological perspectives, this review provides a comprehensive framework for advancing precision-guided periodontal therapy and supports the shift toward targeted, sustainable, and personalized treatment strategies.