Comparative efficacy and safety of oral azithromycin versus doxycycline in moderate-to-severe Acne vulgaris: a systematic review and meta-analysis
Clinical Snapshot
PICO Framework
| P — Population | Patients with moderate to severe acne vulgaris |
| I — Intervention | Oral azithromycin pulse therapy |
| C — Comparator | Doxycycline |
| O — Outcomes | Global acne severity (GAGS), inflammatory and non-inflammatory lesion counts, safety and tolerability |
Bottom Line
This meta-analysis of 23 studies involving 2,769 patients suggests oral azithromycin pulse therapy may be superior to doxycycline for moderate-to-severe acne, with significantly greater improvement in global acne severity scores and non-inflammatory lesion counts. The evidence shows low heterogeneity and appears robust, though inflammatory lesion reduction was similar between treatments. Azithromycin demonstrated better tolerability with fewer side effects. However, methodological limitations include unclear search strategy details and absence of GRADE assessment. While promising, clinicians should consider antibiotic stewardship principles and individual patient factors. The findings challenge current first-line recommendations favouring doxycycline, but require validation through high-quality randomised controlled trials before definitively changing practice guidelines.
Key Findings
P Value: Not reported but CI excludes null
Effect Size: Mean difference 1.81 points greater reduction with azithromycin
Primary Outcome: Global Acne Grading System (GAGS) reduction significantly favoured azithromycin
Nnt Or Sensitivity: Azithromycin achieved 7.56 fewer non-inflammatory lesions (95% CI -14.33 to -0.79)
Confidence Interval: 95% CI 1.28-2.34
Clinical Application
Both medications readily available; azithromycin pulse therapy may improve compliance compared to daily doxycycline Both azithromycin and doxycycline are PBS-listed for acne treatment. TGA-approved indications support use. RACGP guidelines currently favour doxycycline as first-line, but this evidence may inform future updates Adults and adolescents with moderate to severe acne vulgaris seeking oral antibiotic therapy
Abstract
BACKGROUND: Acne vulgaris is a chronic inflammatory disease and is one of the leading causes of dermatological morbidities among young adults. Doxycycline is widely recommended as first-line therapy for moderate to severe acne; however, its use is limited. OBJECTIVE: To systematically compare the efficacy and safety of oral azithromycin pulse therapy versus doxycycline in patients with moderate to severe acne vulgaris. METHODS: This systematic review and meta-analysis followed PRISMA guidelines. A comprehensive literature search on different databases was performed. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Mean differences (MDs) and risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models based on heterogeneity. RESULTS: A total of 23 comparative studies comprising 2,769 patients were included. Pooled analysis demonstrated a statistically significant improvement in global acne severity favoring azithromycin (GAGS reduction: MD 1.81; 95% CI 1.28-2.34; I2 = 0%). Azithromycin achieved a significantly greater reduction in non-inflammatory lesion counts (MD -7.56; 95% CI -14.33 to -0.79). No significant differences were observed in inflammatory lesion reduction (MD 1.08; 95% CI -0.03 to 2.18). CONCLUSION: Oral azithromycin pulse therapy appears to have similar efficacy, better tolerability, and fewer side effects as compared to doxycycline.
References
- 1.Batool, A., Abbas, M. S., Ali Akbar, M., Murtaza, M., Mahin, F. E., Ali, U., Ahmed, A., Khattak, M. H., Fazal, M., Maryam, Z., Yaqoob, R., Silva Correia, J. V., & Aminpoor, H. (2026). Comparative efficacy and safety of oral azithromycin versus doxycycline in moderate-to-severe Acne vulgaris: a systematic review and meta-analysis. *The Journal of Dermatological Treatment*. https://doi.org/10.1080/09546634.2026.2648406
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