Background Mycoplasma genitalium (MG) is an emerging important STI. Failure rates with azithromycin 1 g appear to be increasing. This may be due to the emergence of macrolide antimicrobial resistance as a consequence of extensive use of azithromycin 1 g. An extended regimen of azithromycin 500 mgs on day one then 250 mgs daily for 4 days (5 day regimen) was introduced in the 1990s for treatment of MG and has high efficacy rates (if no pre-existing macrolide resistance) and is less associated with induction of macrolide resistance. There are no comparative trials of the two regimens.

Aim To undertake a meta-analysis of MG treatment studies using the two azithromycin regimens to determine which is more effective.

Methods MG treatment studies were included if: patients were initially assessed for macrolide resistance genetic mutations, were treated with azithromycin 1 g or 5 days, and those who failed were again resistance genotyped. Sensitivity analyses included only patients without prior treatment.

Results Five studies were identified. Compared to the 5 day regimen, azithromycin 1 g had higher failure risk (difference: 11.8%, 95% CI: 7.3%, 16.2%) and more developed macrolide resistance (risk difference: 11.8% (8.3%, 15.3%)). The 5 day regimen included 52 patients with prior doxycycline treatment. Sensitivity analysis showed a failure risk difference of 9.2% (0.9%, 17.5%). Resistance risk did not change.

Conclusion Azithromycin 1 g is more likely to result in treatment failure and the development of macrolide antimicrobial resistance than 500 mgs on day one then 250 mgs daily for 4 days.