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Systematic review and meta-analysis compares oral azithromycin and doxycycline for moderate to severe acneAzithromycin may work better than doxycycline for some acne cases

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Key Takeaway
Consider azithromycin may improve acne severity more than doxycycline, but evidence is observational and safety data are limited.

This is a systematic review and meta-analysis of oral azithromycin pulse therapy compared to doxycycline for patients with moderate to severe acne vulgaris. The analysis included 2,769 patients and synthesized evidence on global acne severity, non-inflammatory lesion counts, and inflammatory lesion reduction.

The authors found a statistically significant improvement in global acne severity, measured by GAGS reduction, favoring azithromycin (MD 1.81, 95% CI 1.28-2.34). Non-inflammatory lesion counts showed a significantly greater reduction with azithromycin (MD -7.56, 95% CI -14.33 to -0.79). However, no significant differences were observed for inflammatory lesion reduction (MD 1.08, 95% CI -0.03 to 2.18).

The review noted that azithromycin appeared to have better tolerability and fewer side effects compared to doxycycline. Adverse events, serious adverse events, and discontinuations were not reported in the source evidence.

Limitations of the synthesis were not detailed by the authors. Practice relevance should be interpreted cautiously, as the evidence is observational and does not establish causality.

A major review of past studies looked at two antibiotics for moderate to severe acne. The research compared oral azithromycin pulse therapy to doxycycline. The main goal was to see how each drug changed overall acne severity.

The review included data from over 2,700 patients. It found that azithromycin led to a greater improvement in overall acne scores than doxycycline. The difference was small but clear. Azithromycin also caused a bigger drop in non-inflammatory bumps like blackheads.

However, there was no major difference between the drugs for reducing red, inflamed pimples. The studies did not report on side effects in detail, but the review suggested azithromycin might be easier to tolerate with fewer issues than doxycycline.

This research helps doctors and patients choose between these two common acne treatments. It suggests azithromycin could be a good option, especially for people who have trouble with doxycycline. More studies are needed to confirm these findings and check long-term safety.

What this means for you:
Azithromycin pulse therapy may improve acne better than doxycycline with fewer side effects.

Study Details

Study typeMeta analysis
Sample sizen = 2,769
EvidenceLevel 1
PublishedDec 2026
View Original 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; I = 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.
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