Mycoplasma genitalium (Mgen) is treated with a resistance-guided, two-step antibiotic course that always starts with doxycycline. After the doxycycline lead-in, you take azithromycin if your strain is macrolide-susceptible, or moxifloxacin if it's macrolide-resistant. A single dose of azithromycin alone now fails too often to be reliable CDC, 2021.
rising — guides therapy
doxy → moxifloxacin
| Item | Value |
|---|---|
| US adults infected | ~1–2% |
| Azithromycin resistance | ~50% — rising — guides therapy |
| Often | no symptoms |
| Treatment | resistance-guided — doxy → moxifloxacin |
Why Mgen is harder to treat than other STIs
Mycoplasma genitalium is an unusual bug. It has no cell wall, so the entire family of beta-lactam antibiotics — penicillins and cephalosporins — has nothing to attack and does nothing against it. That rules out the drugs that knock out infections like gonorrhea. Mgen is an emerging cause of urethritis (inflammation of the urethra, the tube urine passes through) in men and cervicitis (inflammation of the cervix) in women, and treating it is hard because of antibiotic resistance, especially to the macrolide class that includes azithromycin.
That resistance has crept up quietly. Macrolide-resistance mutations now exceed half of cases in many areas — over 62% in one US STI clinic — and that's why the old single azithromycin dose so often leaves the infection behind. If you want the bigger picture first, see why awareness is key in mg diagnosis and treatment.
How Mgen is treated: the regimen and exact doses
Current CDC guidance is resistance-guided and two-step, and it always opens with doxycycline. The doxycycline lead-in lowers the bacterial load so the second drug has fewer organisms to clear, which improves the odds of cure. What comes next depends on whether your strain carries a macrolide-resistance mutation, which comes from a specific resistance test rather than a guess.
- If the strain is macrolide-sensitive: doxycycline 100 mg twice daily for 7 days, then azithromycin 1 g once, followed by 500 mg daily for 3 days.
- If the strain is macrolide-resistant, or resistance testing isn't available: doxycycline 100 mg twice daily for 7 days, then moxifloxacin 400 mg daily for 7 days.
A standard STI panel can't tell your clinician which second-line drug you actually need, so a dedicated M. genitalium test matters. The right test detects the organism and, ideally, the resistance mutation in one go. For how that test works and how to ask for it, see our guide to mgen testing.
| Scenario | Step 1 (lead-in) | Step 2 (clearing dose) |
|---|---|---|
| Macrolide-sensitive strain | Doxycycline 100 mg twice daily for 7 days | Azithromycin 1 g once, then 500 mg daily for 3 days |
| Macrolide-resistant strain or testing unavailable | Doxycycline 100 mg twice daily for 7 days | Moxifloxacin 400 mg daily for 7 days |
What treatment is actually like
This is a defined course of pills taken over a couple of weeks, not a one-and-done shot. The two phases run back-to-back: you finish the doxycycline first, then start the second drug. Doxycycline can upset the stomach and makes some people more sensitive to sunburn, so take it with food and a full glass of water and don't lie down right after. Moxifloxacin is a fluoroquinolone, a class that occasionally causes tendon and nerve side effects, so flag any new joint or tendon pain to your clinician.
Finish every pill even after symptoms fade. Stopping early lets resistant Mgen survive and come back harder to treat. Don't reproduce a regimen from an old prescription or a friend's leftovers — the legacy single azithromycin dose is the approach this guidance specifically moved away from.
Do partners need treatment?
Reinfection is why Mgen lingers: you clear it, then catch it back from an untreated partner. Current sexual partners of someone with symptomatic infection can be tested and treated if they're positive, which lowers that ping-pong risk NYSDOH/Johns Hopkins. Practically, that means telling recent partners so they can get checked, and avoiding sex until both of you have completed treatment. Understanding how mycoplasma genitalium spreads makes the partner conversation easier to have honestly.
Follow-up and test-of-cure
Because failure is common with this organism, follow-up matters more here than with many other STIs. If symptoms persist after you finish the full course, go back — a continued infection may mean the strain was resistant or that you were reinfected, and your clinician may switch to the moxifloxacin regimen or repeat testing. Don't assume lingering symptoms mean the antibiotics failed entirely; sometimes residual irritation settles, but it's worth a check rather than a guess. If you're trying to time any retest after a new exposure, our guide on when to test after exposure explains the windows.
What happens if Mgen goes untreated
Left alone, Mgen doesn't just stay a nuisance. In women it's linked to cervicitis, pelvic inflammatory disease (PID — infection that spreads to the uterus and fallopian tubes and can scar them), preterm delivery, and infertility, with roughly a twofold increased risk of infertility. In men, untreated infection commonly shows up as persistent or recurrent urethritis — that nagging discharge or burning that keeps coming back despite treatment for something else.
None of these complications are inevitable. They're the reason treating Mgen properly, and confirming it cleared, is worth the effort rather than waiting it out.
Preventing reinfection going forward
Condoms used every time lower the risk of catching or passing Mgen, and they're the most reliable tool you control. Routine STI screening catches infections that cause no symptoms at all, which is how a lot of Mgen travels. After you've been treated, consistent condom use plus making sure partners were treated keeps it from coming back.
- Use condoms consistently — every time, not just when you remember.
- Make sure recent partners are tested and treated so you don't reinfect each other.
- Finish the full antibiotic course and return if symptoms don't resolve.
- Build routine screening into your care; you can get tested even without symptoms.
When to see a clinician
See a clinician for burning with urination, unusual discharge, pelvic pain, or any urethral or cervical symptoms that don't clear — especially if you've already been treated for another infection and the symptoms came back. Testing is straightforward: usually a urine sample or a self-collected swab, with results typically back in a few days, and it's free or low-cost at health departments, Planned Parenthood, and Title X clinics. Clinics deal with this diagnosis daily, and it says nothing about you as a person. If you're choosing where to go, you can compare testing providers.