What is the recommended treatment for Mycoplasma genitalium and Ureaplasma infections?

Treatment of Mycoplasma genitalium and Ureaplasma Infections

Mycoplasma genitalium Treatment

For M. genitalium infections, azithromycin 500 mg on day 1, followed by 250 mg daily on days 2-5 is the preferred first-line treatment, achieving 93-99% cure rates while minimizing macrolide resistance development. 1, 2, 3

First-Line Treatment Strategy

• Extended-dose azithromycin (500 mg day 1, then 250 mg days 2-5) is superior to single-dose azithromycin 1g, with cure rates of 99% versus 91% 3
• The extended regimen critically prevents macrolide resistance development—single-dose azithromycin 1g selected for resistance in 100% of treatment failures, while extended dosing selected resistance in 0% 3
• Doxycycline 100 mg twice daily for 7 days is an alternative but achieves only 30-40% cure rates and should not be used as monotherapy 2, 4, 5

Resistance-Guided Approach

Testing for macrolide resistance mutations before treatment is essential given rising resistance rates (0% in 2006-2007 to 18% by 2011, and continuing to increase). 5, 3

• For macrolide-susceptible infections: Use extended-dose azithromycin as above 5
• For macrolide-resistant infections: Moxifloxacin 400 mg once daily for 7 days (uncomplicated) or 14 days (complicated infections like PID/epididymitis) 4, 5

Combination Therapy for Resistant Cases

Recent evidence supports combination therapy for improved cure rates:

• Doxycycline 100 mg twice daily for 7 days PLUS azithromycin (extended dose) for macrolide-susceptible infections achieved 93% cure 6
• Doxycycline 100 mg twice daily for 7 days PLUS moxifloxacin 400 mg daily for 7 days for macrolide-resistant infections achieved 85% overall cure, but 98.3% cure when parC mutations at S83/D87 were absent 6

Critical Caveat: Fluoroquinolone Resistance

• The parC S83I mutation is now present in 23% of macrolide-resistant infections and causes 62.5% treatment failure with moxifloxacin 6
• If parC resistance testing is available, avoid moxifloxacin when S83I or D87 mutations are detected 6
• Moxifloxacin cure rates have declined from 100% pre-2010 to 89% post-2010 7

Third-Line Options for Persistent Infection

When both azithromycin and moxifloxacin fail:

• Doxycycline or minocycline 100 mg twice daily for 14 days may cure 40-70% 5
• Pristinamycin 1g four times daily for 10 days achieves approximately 75-90% cure 4, 5

Follow-Up Requirements

• Patients must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of multi-day regimens 8, 1, 2
• Test of cure is recommended 14-28 days after treatment completion, particularly given rising resistance 6
• Partners require evaluation and treatment to prevent reinfection 1, 2

Ureaplasma Treatment

The provided evidence does not contain specific treatment guidelines for Ureaplasma species. The 2010 CDC guidelines focus on non-gonococcal urethritis broadly but do not distinguish Ureaplasma-specific regimens 8.

Based on the general NGU treatment framework:

• Azithromycin 1g single dose or doxycycline 100 mg twice daily for 7 days are the standard NGU regimens that would cover Ureaplasma 8
• Alternative regimens include erythromycin base 500 mg four times daily for 7 days, levofloxacin 500 mg daily for 7 days, or ofloxacin 300 mg twice daily for 7 days 8

Key Clinical Pitfalls

• Never use azithromycin 1g single dose for M. genitalium—it drives resistance while extended dosing does not 3
• Do not rely on doxycycline monotherapy for M. genitalium—the 30-40% cure rate is unacceptably low 2, 4, 5
• Moxifloxacin warnings: The 2021 European guideline emphasizes restricting moxifloxacin use due to safety concerns and rising resistance 5
• Test all patients for gonorrhea and chlamydia concurrently, as co-infections are common 1, 2