Background Systemic antibiotics for moderate-to-severe acne are commonly prescribed, but the optimal duration remains unclear. Prolonged use may increase recurrence rates and antibiotic resistance. This study evaluated the long-term effects of antibiotic duration on acne recurrence and microbial resistance. Methods This study included a single-center retrospective cohort of 240 patients (12–40 years) with moderate-to-severe acne treated with doxycycline or minocycline (2020–2023). Patients were stratified into groups by duration: short-term (6–12 weeks, n = 80), standard-term (13–16 weeks, n = 80), and prolonged (17–24 weeks, n = 80) groups. The primary outcome was the 12-month recurrence rate. Secondary outcomes included 12-week treatment success, scarring, adverse reactions, and resistance development (culture subset, n = 46). Results The 12-month recurrence rates increased in a duration-dependent manner: 23.8% (short-term duration), 35.0% (standard-term duration), and 46.3% (prolonged duration) ( p < 0.001). The median recurrence-free survival was 9.2, 8.1, and 6.9 months, respectively (log-rank p < 0.001). Prolonged exposure independently predicted recurrence (adjusted hazard ratio (HR): 2.31, 95%CI 1.31–4.07, p = 0.004). The 12-week success rates were similar (73.8–76.3%, P=0.78). Scarring (21.3–22.5%, p = 0.97) and adverse events (27.5–31.3%, p = 0.83) did not differ. Tetracycline resistance was more frequent with prolonged exposure (42.9% vs. 13.3–17.6%, p = 0.032). Conclusion Extended antibiotic therapy for acne was associated with an increased 12-month recurrence risk without improving short-term outcomes, consistent with guideline recommendations to limit duration and emphasize antimicrobial stewardship.
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