Amoxicillin/clavulanate as a cornerstone of antibiotic stewardship: integrating WHO AWaRe principles, Italian recommendations, and evidence-based practice.

Antimicrobial resistance (AMR) remains a critical global health concern, largely driven by inappropriate antibiotic use. To address this challenge, the World Health Organization (WHO) developed the AWaRe (Access, Watch, Reserve) classification, prioritizing the use of Access antibiotics - narrow-spectrum agents with proven efficacy and low resistance potential. Amoxicillin/clavulanate, included in the Access group, is widely endorsed in international and national guidelines, as a first-line option for common community-acquired infections. This Expert Opinion reviews the positioning of amoxicillin/clavulanate within stewardship frameworks, synthesizing its pharmacological characteristics, clinical evidence, and relevance in both Italian and global contexts. The combination of amoxicillin with the β-lactamase inhibitor clavulanic acid provides broad activity against key respiratory pathogens such as Haemophilus influenzae, and Moraxella catarrhalis, including β-lactamase-producing strains. Evidence from randomized controlled trials and meta-analyses demonstrates high bacteriological eradication and clinical cure rates across acute bacterial rhinosinusitis, otitis media, community-acquired pneumonia, and chronic bronchitis exacerbations. In pediatric populations, amoxicillin/clavulanate has shown significant efficacy in protracted bacterial bronchitis and chronic wet cough. Comparative data confirm its equivalence or superiority to macrolides and fluoroquinolones while maintaining a lower resistance selection potential and favorable tolerability. The integration of WHO AWaRe targets, Italian stewardship recommendations, and robust clinical evidence underscores the central role of amoxicillin/clavulanate in rational antibiotic prescribing. Its stewardship-aligned use - emphasizing short-course therapy, targeted prescribing, and avoidance in viral syndromes - represents a pragmatic and evidence-based strategy to optimize treatment outcomes while contributing to AMR mitigation in both national and global contexts.