Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis

Background: There is increasing evidence that azithromycin 1g is driving the emergence of macrolide resistance in M. genitalium worldwide. We undertook a meta-analysis of Mycoplasma genitalium treatment studies using azithromycin 1g single dose, and azithromycin 500 mgs on day one then 250mgs 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 “Mycoplasma genitalium”, “macrolide” or “azithromycin” and “resistance” up to April 2016. Studies were eligible if they: used azithromycin 1g 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 totaling 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 1g was 13.9% (95% Confidence Interval: 7.7-20.1%) and 12.0% (7.1-16.9%) respectively. Of individuals treated with the 5 day regimen, with no prior doxycycline treatment, fewer 3.7% (95% CI: 0.8-10.3, p=0.012) failed treatment, all of whom developed resistance (p=0.027).

Conclusion: Azithromycin 1g is associated with high rates of treatment failure and development of macrolide resistance in M. genitalium 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.