Azithromycin in crisis: antimicrobial resistance, diagnostics gaps, and vaccine-linked stewardship for enteric infections in low- and middle-income countries

Azithromycin has become a cornerstone oral therapy for enteric infections in low- and middle-income countries (LMICs), driven by rising fluoroquinolone resistance, favorable pharmacokinetics, and limited access to diagnostics and parenteral antibiotics. However, escalating resistance among key enteric pathogens including Shigella , typhoidal and non-typhoidal Salmonella , and Campylobacter now threatens its clinical utility. This commentary argues that azithromycin resistance reflects systemic health-system failures rather than isolated microbiological evolution. Prolonged empirical use, driven by diagnostic gaps, over-the-counter availability, and weak stewardship, has intensified selective pressure, compounded by azithromycin’s long half-life, high intestinal exposure, and primarily bacteriostatic activity. Resistance mechanisms and clinical impact vary substantially across pathogens, underscoring the limitations of uniform treatment approaches. We highlight the central role of accessible diagnostics, pathogen-directed stewardship, enteric pathogen surveillance, and vaccination as antimicrobial resistance mitigation strategies. Preserving azithromycin requires integrated, health-system–level interventions that align diagnostics, stewardship, surveillance, and prevention to sustain one of the last effective oral options for severe enteric infections in LMICs.