What is the recommended treatment for mycoplasma genitalium?

Treatment for Mycoplasma Genitalium

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

Diagnostic Testing Before Treatment

• Test all patients with urethritis, cervicitis, or related genital tract infections for M. genitalium using nucleic acid amplification testing (NAAT), as this is the only reliable diagnostic method 2, 3.
• Always test simultaneously for gonorrhea and chlamydia, as co-infections are common 2.
• If available, perform macrolide resistance testing after NAAT diagnosis to guide therapy selection 4.

First-Line Treatment Regimen

Azithromycin extended course is superior to single-dose therapy:

• Preferred regimen: Azithromycin 500 mg orally on day 1, then 250 mg daily on days 2-5 1, 3, 4.
• This extended dosing achieves 93-99% cure rates compared to only 84% with single-dose azithromycin 1g 1, 5.
• The extended course minimizes selection of macrolide resistance 1.

Important caveat: While CDC guidelines mention azithromycin 1g single dose 2, this regimen has unacceptable failure rates (16% persistent infection) and should be avoided 5. The European guidelines and recent research strongly support the extended 5-day course 3, 4.

Resistance-Guided Combination Therapy (Optimal Approach)

For patients where resistance testing is available, a resistance-guided strategy achieves the highest cure rates:

• All patients receive doxycycline 100 mg twice daily for 7 days first 6, 7.
• Macrolide-susceptible infections: Follow with azithromycin 1g on day 1, then 500 mg daily for days 2-4 (achieving 95.7% cure) 6, 7.
• Macrolide-resistant infections: Follow with moxifloxacin 400 mg daily for 7 days (achieving 85-92% cure) 6, 7.

Critical resistance consideration: If parC gene mutations at positions S83 or D87 are present (particularly S83I), moxifloxacin failure rates reach 62.5% 7. In wild-type parC infections, moxifloxacin achieves 98.3% cure 7.

Second-Line Treatment for Treatment Failures

• Moxifloxacin 400 mg orally once daily for 7-10 days for uncomplicated infections that failed azithromycin 3, 4.
• Extend moxifloxacin to 14 days for complicated infections (PID, epididymitis) 3, 4.
• Moxifloxacin eradicated all persistent infections following azithromycin failure in one study 5.

Third-Line Options for Persistent Infection

• Doxycycline 100 mg twice daily for 14 days may cure 40-70% of persistent infections 4.
• Pristinamycin 1g four times daily for 10 days achieves approximately 75-90% cure rates 3, 4.

Why Doxycycline Monotherapy Should Be Avoided

• Doxycycline achieves only 30-40% cure rates and should never be used as monotherapy 2, 1, 3, 4.
• However, doxycycline does not increase resistance and may decrease organism load when used before azithromycin or moxifloxacin 4, 7.

Follow-Up Requirements

• Patients must abstain from sexual intercourse for 7 days after single-dose therapy or until completion of multi-day regimens 2, 1.
• All sexual partners require evaluation and treatment to prevent reinfection 2, 1.
• Test of cure is recommended 14-28 days post-treatment, particularly given rising resistance rates 6, 7.
• Patients with persistent symptoms after treatment are highly likely to have persistent infection (91% correlation) and require retesting 5.

Key Clinical Pitfalls

• Avoid azithromycin 1g single dose: This regimen has contributed to widespread macrolide resistance (now exceeding 50% in many regions) and has unacceptable failure rates 5, 4.
• Macrolide resistance is increasing dramatically: Always consider resistance-guided therapy when testing is available 4, 7.
• Quinolone resistance is emerging: ParC mutations are present in 22-29% of macrolide-resistant cases, significantly reducing moxifloxacin efficacy 6, 7.