What is the recommended treatment for mycoplasma genitalium?

Treatment for Mycoplasma Genitalium

Recommended First-Line Treatment

The optimal first-line treatment for Mycoplasma genitalium is azithromycin 500 mg orally on day 1, followed by 250 mg daily on days 2-5, which achieves 93-99% cure rates while minimizing macrolide resistance development 1.

This extended azithromycin regimen is superior to the single 1 g dose, which has unacceptably high failure rates of 16% even without partner reinfection risk 2. The extended dosing strategy reduces selection pressure for macrolide resistance compared to single-dose therapy 3, 4.

Pre-Treatment Considerations

• Always test for macrolide resistance mutations before initiating therapy when testing is available, as macrolide resistance now exceeds 50% in many regions 4, 5.
• Test simultaneously for gonorrhea and chlamydia, as co-infections are common 6.
• Resistance-guided therapy significantly improves outcomes and prevents treatment failures 5, 7.

Alternative First-Line Strategy: Combination Therapy

For macrolide-susceptible infections confirmed by resistance testing:

• Doxycycline 100 mg orally twice daily for 7 days, followed immediately by azithromycin 1 g on day 1, then 500 mg daily for days 2-4 achieves 93-95% cure rates 5, 7.
• The doxycycline pre-treatment reduces organism load and may decrease macrolide resistance selection 4, 5.

Treatment for Macrolide-Resistant Infections

For confirmed macrolide-resistant M. genitalium, use doxycycline 100 mg twice daily for 7 days followed by moxifloxacin 400 mg daily for 7 days 4, 5, 7.

Critical Caveat on Moxifloxacin Efficacy:

• This regimen achieves only 85% cure overall due to emerging quinolone resistance 7.
• If parC gene sequencing is available and shows wild-type (no mutations at S83 or D87), cure rates reach 98.3% with doxycycline-moxifloxacin 7.
• The presence of parC S83I mutation predicts 62.5% treatment failure with moxifloxacin 7.
• ParC mutations are present in 22-29% of macrolide-resistant cases 5, 7.

Treatment for Complicated Infections

For pelvic inflammatory disease or epididymitis caused by M. genitalium:

• Moxifloxacin 400 mg daily for 14 days (extended duration) 3, 4.

Third-Line Options for Persistent Infection

When both azithromycin and moxifloxacin have failed:

• Doxycycline 100 mg twice daily for 14 days may cure 40-70% 4.
• Pristinamycin 1 g four times daily for 10 days achieves approximately 75% cure 4.

Follow-Up Requirements

• Patients must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of multi-day regimens 6, 1.
• Test of cure is recommended 14-28 days after antimicrobial completion, particularly given high resistance rates 5, 7.
• Partners require evaluation and treatment to prevent reinfection 6, 1.
• Patients with persistent M. genitalium experience ongoing symptoms in 91% of cases, compared to only 17% when infection is eradicated 2.

Common Pitfalls to Avoid

• Never use doxycycline monotherapy—it achieves only 30-40% cure rates and should not be relied upon alone 6, 1, 3, 4.
• Avoid azithromycin 1 g single dose as monotherapy, which has contributed to widespread macrolide resistance through inadequate treatment 3, 4.
• Side effects from combination therapy are common (40-46%) but predominantly mild and gastrointestinal 7.
• The FDA label for azithromycin does not specifically list M. genitalium as an approved indication, though it covers urethritis and cervicitis due to Chlamydia trachomatis 8.