Efficacy and tolerability of the combination of minocycline and metronidazole for macrolide-resistant Mycoplasma genitalium

Background and objectives Curing Mycoplasma genitalium is challenging in the context of rising antimicrobial resistance and limited therapeutic options. There is an urgent need for globally relevant and effective treatment options using readily available and affordable agents. From September 2021 to August 2024 at Melbourne Sexual Health Centre, we prospectively evaluated microbial cure and tolerability of oral minocycline 100 mg combined with metronidazole 400 mg (twice daily for 14 days) for individuals with macrolide-resistant M. genitalium in whom fluroquinolones had failed or were not advised. Methods Microbial cure was defined as a negative test of cure (TOC) using transcription-mediated amplification 14-90 days after completing the regimen. The proportion cured and 95% confidence intervals (CIs) were calculated. Data on side effects and adherence were collected at TOC visits. Results Microbial cure in patients receiving the combination regimen was 80.8% (95% CI: 71.9-87.8%). Cure in those who had received preceding doxycycline was 90.3% (n = 28/31, 95% CI: 74.2-98.0%) compared to 76.7% (n = 56/73, 95% CI: 65.4-85.8%) in those who had not, P = 0.172. Central nervous system and gastrointestinal side effects were commonly reported. Conclusions Minocycline with metronidazole cured 80% of macrolide-resistant infections in this cohort. Cure may be enhanced by the use of doxycycline before the combination regimen but larger studies are needed. Given limited options for treating resistant M. genitalium infections, the combined minocycline and metronidazole regimen may represent a promising option where no alternative drugs are available, or quinolones are contraindicated. Clinicians should be aware of and discuss side effects with patients.