Which Azithromycin Regimen Should Be Used for Treating ? A Meta-analysis

Background: There is increasing evidence that azithromycin 1 g is driving the emergence of macrolide resistance in worldwide. We undertook a meta-analysis of treatment studies using azithromycin 1 g single dose and azithromycin 500 mg on day 1 then 250 mg daily for 4 days (5-day regimen) to determine rates of treatment failure and resistance in both regimens.

Methods: The online databases PubMed and Medline were searched using terms "", " or " and " up to April 2016. Studies were eligible if they: used azithromycin 1 g or 5 days, assessed patients for macrolide resistant genetic mutations prior to treatment and patients who failed were again resistance genotyped. Random effects meta-analysis was used to estimate failure and resistance rates.

Results: Eight studies were identified totalling 435 patients of whom 82 (18.9%) had received the 5-day regimen. The random effects pooled rate of treatment failure and development of macrolide antimicrobial resistance mutations with azithromycin 1 g was 13.9% (95% CI 7.7% to 20.1%) and 12.0% (7.1% to 16.9%), respectively. Of individuals treated with the 5-day regimen, with no prior doxycycline treatment, fewer (3.7%; 95% CI 0.8% to 10.3%, p=0.012) failed treatment, all of whom developed resistance (p=0.027).

Conclusion: Azithromycin 1 g is associated with high rates of treatment failure and development of macrolide resistance in infection with no pre-existing macrolide mutations. There is moderate but conflicting evidence that the 5-day regimen may be more effective and less likely to cause resistance.