Awareness is the difference between curing Mycoplasma genitalium on the first try and chasing a stubborn, recurring infection. Because this bug has no cell wall and is increasingly resistant to common antibiotics, it needs a specific test and a two-step, resistance-guided regimen: doxycycline first, then either azithromycin or moxifloxacin depending on the strain.
At a glance
- Doxycycline → Azithromycin
- 95.4% cure
- Used when strain is macrolide-susceptible
- Doxycycline → Moxifloxacin
- 92.0% cure
- Used when strain is macrolide-resistant or testing unavailable
- New macrolide resistance
- 4.6%
- Emerged among treated cases in the trial
| Item | Value |
|---|---|
| Doxycycline → Azithromycin | 95.4% cure: Used when strain is macrolide-susceptible |
| Doxycycline → Moxifloxacin | 92.0% cure: Used when strain is macrolide-resistant or testing unavailable |
| New macrolide resistance | 4.6%: Emerged among treated cases in the trial |
Mycoplasma genitalium, often shortened to Mgen or MG, is an emerging cause of urethritis in men and cervicitis in women, and it's the hardest of the common sexually transmitted bacteria to treat. The reason is structural: it lacks a cell wall, so beta-lactam antibiotics like penicillins and cephalosporins simply have nothing to attack CDC, 2021. Combine that biology with sky-high macrolide resistance and you have an infection where knowing the strain matters more than with almost any other STI. If you're new to this infection, start with our plain-language guide to mycoplasma genitalium.
How Mycoplasma genitalium is treated
Current CDC guidance calls for resistance-guided, two-step therapy that always opens with doxycycline. Doxycycline alone clears only a minority of infections, roughly 30%: 40% effective as monotherapy CDC, 2022, but it knocks down the bacterial load so the second drug can finish the job. What comes second depends on whether the strain carries macrolide-resistance mutations.
If the strain is macrolide-susceptible, the regimen is doxycycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g as an initial dose then 500 mg once daily for 3 additional days (2.5 g total). If the strain is macrolide-resistant, or resistance testing isn't available, the second drug switches to moxifloxacin 400 mg once daily for 7 days after the same doxycycline lead-in.
This is a real change from the old playbook. For years a single 1-g dose of azithromycin was standard, but that approach now selects for resistant bacteria in roughly 10%: 12% of treated infections, so CDC recommends against single-dose azithromycin and in favor of the staged regimen. In the resistance-guided therapy trial by Read and colleagues, microbial cure reached 95.4% with doxycycline, azithromycin and 92.0% with doxycycline, moxifloxacin, with new macrolide resistance emerging in only 4.6% of cases Read et al., Resistance-Guided Therapy RCT, Clin Infect Dis 2019.
| Scenario | Step 1 | Step 2 |
|---|---|---|
| Macrolide-susceptible | Doxycycline 100 mg twice daily × 7 days | Azithromycin 1 g, then 500 mg daily × 3 days (2.5 g total) |
| Macrolide-resistant or testing unavailable | Doxycycline 100 mg twice daily × 7 days | Moxifloxacin 400 mg once daily × 7 days |
Molecular markers of macrolide resistance closely predict treatment failure, and they run from 44% to as high as 90% across the U.S., Canada, Western Europe, and Australia. In some U.S. STI clinics, resistance mutations exceed 62% of infections. Treating blind is a coin flip. The Aptima Mycoplasma genitalium assay, FDA-approved in 2019, is currently the only NAAT cleared for this organism AAFP, 2021, and some labs can also run a reflex resistance assay that tells your clinician which step-2 drug to pick.
What treatment is actually like
Practically, this is a defined course of pills: no shot, no cream. You'll start the doxycycline phase first, then move to the second antibiotic. Doxycycline can upset your stomach and make your skin more sensitive to sun, so take it with food and water and stay out of strong sun. Finish every dose even after symptoms fade. Stopping early is one of the main reasons Mgen comes back resistant.
Avoid sex until you've completed the full regimen and any retest your clinician orders. Tell your provider about other medications, since moxifloxacin in particular interacts with several drugs and isn't right for everyone. Clinics handle this diagnosis routinely, and it says nothing about you as a person.
Partner treatment
Reinfection is the silent saboteur. Partners of someone with symptomatic Mgen can be tested and treated if positive, the most reliable way to stop the two of you from passing it back and forth. Because resistance can differ between partners, ideally each person is treated based on their own test result rather than one prescription copied across the couple. We walk through the specifics in our guide to Mgen partner treatment.
Follow-up, retest, and test-of-cure
A test-of-cure is more relevant for Mgen than for most STIs because failure is common enough to expect. Your clinician will usually recommend repeat NAAT testing a few weeks after you finish treatment to confirm the bacteria are gone: wait the full interval they specify, since testing too soon can detect dead organism fragments and give a false positive. If symptoms persist or the retest is still positive, the strain may be resistant, and your provider may move to the moxifloxacin pathway or seek specialist input.
If you're testing because of a recent exposure rather than symptoms, timing matters, see our explainer on when to test after exposure so you don't test too early and miss it.
What happens if Mgen goes untreated
Left untreated, Mgen isn't harmless. In men it causes 20%, 30% of urethritis cases and tends to produce persistent or recurrent urethritis, inflammation of the urethra that brings discharge, burning on urination, and irritation that won't resolve. In women it's linked to a roughly twofold increased risk of several conditions: cervicitis (inflammation of the cervix), pelvic inflammatory disease (a deeper infection of the uterus and tubes that can scar the reproductive tract), preterm delivery, and infertility. None of these are guaranteed, but they're why ignoring a positive result isn't a safe gamble.
Mgen can also colonize sites beyond the genitals; if you have throat symptoms or oral exposure, read about Mgen in the throat for what's known and what isn't.
Prevention going forward
Condoms used every time lower transmission risk, and routine STI testing catches infections that produce no symptoms at all. Many Mgen infections are silent. General-population prevalence is estimated around 1.3% in higher-development countries Mgen & T. vaginalis, so it isn't rare. If you've been treated, the best protection against reinfection is making sure your partner gets evaluated. When you're choosing where to go, you can compare testing providers for cost and turnaround.
- Use condoms consistently with new or untreated partners.
- Ask specifically for an Mgen test: it's not on standard STI panels, so you may have to request it.
- Finish every dose of both antibiotics, even after you feel fine.
- Don't resume sex until you've completed treatment and any test-of-cure your clinician orders.
When to see a clinician
See a clinician if you have burning with urination, unusual genital or urethral discharge, pelvic pain, bleeding between periods or after sex, or urethritis symptoms that didn't clear after a previous round of antibiotics, which is a classic Mgen presentation. Testing is straightforward: most cases are diagnosed from a urine cup or a self-collected swab, with results usually back in a few days, and it's free or low-cost at health departments, Planned Parenthood, and Title X clinics. You can get tested confidentially without a big production.
Keep exploring on EasySTD: STD incubation periods, how and where to get tested and Mycoplasma genitalium testing.