Azithromycin in Dentistry: From Systemic Antibiotic to a Candidate for Local Therapeutic Delivery

Azithromycin is widely used in dentistry as a systemic antibiotic, particularly for odontogenic infections and as an alternative in patients with β-lactam hypersensitivity. Beyond its antimicrobial activity, azithromycin possesses unique pharmacokinetic, anti-inflammatory, immunomodulatory, and anti-biofilm properties. Together with growing concerns regarding antimicrobial resistance and antibiotic stewardship, these characteristics have stimulated interest in local drug-delivery strategies that may reduce systemic antibiotic exposure while maintaining therapeutic efficacy. This narrative review evaluates the rationale, potential clinical applications, and current evidence supporting local azithromycin delivery in dentistry. The available literature on azithromycin pharmacology, systemic dental use, immunomodulatory mechanisms, biofilm-related effects, local drug-delivery systems, safety, and regulatory considerations was critically reviewed. Current evidence suggests that locally delivered azithromycin may achieve high drug concentrations at the target site, enhance anti-biofilm activity, modulate local inflammation, and minimize systemic exposure. Potential applications include periodontitis, peri-implant diseases, persistent endodontic infections, oral surgery, and regenerative procedures such as bone augmentation and maxillary sinus floor elevation. Emerging delivery platforms, such as hydrogels, thermoresponsive gels, nanoparticles, and chitosan-based systems, further support the feasibility of this approach. Experimental findings also indicate that azithromycin may inhibit osteoclast activity, suggesting additional benefits for bone preservation and regenerative healing. Despite these promising findings, current evidence remains limited and is derived mainly from preclinical studies and small clinical investigations. Further translational research and well-designed randomized controlled trials are needed to establish the safety, efficacy, and optimal clinical role of locally delivered azithromycin in evidence-based dental practice.