Does pre-treatment with doxycycline improve the efficacy of combination minocycline and metronidazole for macrolide-resistant Mycoplasma genitalium infections?

Antimicrobial options for Mycoplasma genitalium are limited. Our prior study found a 14-day regimen of minocycline and metronidazole (minocycline + metronidazole) achieved microbial cure in 76.7% ( n = 56/73, 95% confidence interval [95% CI]: 65.4%–85.8%) of macrolide-resistant infections, with an efficacy of 90.3% ( n = 28/31, 95% CI: 74.2%–98.0%) if preceded by 7 days of doxycycline. We aimed to evaluate the efficacy and tolerability of sequential doxycycline and 14 days of minocycline + metronidazole in a larger cohort. Microbial cure was defined as a negative test-of-cure using transcription-mediated amplification 14–90 days after completing minocycline + metronidazole. The proportion cured and 95% CIs were calculated, and univariable and multivariable logistic regression analyses were performed to examine factors associated with cure. Adverse effect data were collated. Overall, microbial cure following minocycline + metronidazole was 80.9% ( n = 212/262, 95% CI: 75.6%–85.5%). Microbial cure was similar among 181 patients who received doxycycline pre-treatment (82.3%, 95% CI: 76.0%–87.6%) compared with 81 patients without pre-treatment (77.8%, 95% CI: 67.1%–86.3%, P = 0.387); individuals who had failed prior regimens were more likely to experience cure with doxycycline pre-treatment. A higher proportion of cervicovaginal infections were cured following minocycline + metronidazole compared to urethral infections. Gastrointestinal and central nervous system adverse effects were not significantly increased with the addition of doxycycline. In this larger data set, doxycycline pre-treatment did not significantly enhance the efficacy of minocycline + metronidazole. In our setting, cure following minocycline + metronidazole was comparable to cure following moxifloxacin, but this generic regimen is more widely accessible and cures 80% of M. genitalium infections with dual-class resistance. The regimen’s higher efficacy for cervicovaginal infections may reflect a sex-effect and/or its additional influence on vaginal dysbiosis.