Azithromycin Versus Doxycycline in Non-Gonococcal Urethritis

Abstract

Introduction: Antimicrobial resistance is altering treatment guidelines for non-gonococcal urethritis (NGU). This review compares cure rates of azithromycin 1g single dose vs doxycycline 100mg bid for 7 days. Methods: Systematic review of 8 RCTs (n=2,105) from 2015–2025. Primary outcome: microbiologic cure of Chlamydia trachomatis and Mycoplasma genitalium at test-of-cure (3-5 weeks). Results: For C. trachomatis, doxycycline was superior (97% cure vs 91% for azithromycin, p=0.003). For M. genitalium, azithromycin efficacy dropped to 68% due to macrolide resistance, while doxycycline achieved only 45% cure. Discussion: Widespread macrolide resistance in M. genitalium now exceeds 50% in many regions. Doxycycline remains first-line for chlamydia. Dual therapy may be needed for mixed infections. Conclusions: Empiric azithromycin for NGU should be abandoned; doxycycline plus azithromycin or resistance-guided therapy is preferred.