A Comprehensive Review on Sulfonamide Resistance: Recent Trends And Implications in Primary Care Clinical Settings

Sulfonamides, once widely effective antibiotics, now face escalating resistance due to decades of overuse in clinical and agricultural settings. This narrative review synthesizes evidence (2000–2024) on the evolutionary drivers of resistance, highlighting key mechanisms such as folP gene mutations, the acquisition of sul1, sul2, and sul3 resistance genes via mobile genetic elements, and efflux pump activation. Resistance proliferation is exacerbated by environmental contamination—particularly in hospital effluents and manure-treated soils—where antibiotic residues select for resistant strains and facilitate gene transfer to human pathogens. Clinical misuse (e.g., subtherapeutic dosing) further accelerates resistance, complicating infections like UTIs and respiratory diseases. Emerging data underscore the need for integrated strategies: antimicrobial stewardship to curb unnecessary prescriptions, surveillance of resistance hotspots (e.g., wastewater, livestock), and policy reforms to limit agricultural overuse. Combination therapies (e.g., trimethoprim-sulfamethoxazole) may delay resistance, but long-term solutions require a One Health approach. This review equips clinicians with insights to navigate sulfonamide resistance while advocating for systemic interventions to preserve antibiotic efficacy.