Treatment for Mycoplasma genitalium
The recommended first-line treatment is azithromycin 500 mg orally on day 1, followed by 250 mg orally once daily for days 2-5, which achieves 93-99% cure rates while minimizing macrolide resistance development. 1, 2, 3
Diagnostic Testing Before Treatment
- Confirm M. genitalium infection using nucleic acid amplification testing (NAAT) before initiating therapy, as this is the only reliable diagnostic method available 1, 4
- Test simultaneously for gonorrhea and chlamydia, since co-infections are common and require different treatment approaches 1, 2
- When available, perform macrolide resistance testing to guide therapy selection, as resistance rates have increased dramatically (from 0% in 2006-2007 to 18% by 2011 in some populations) 5, 4, 6
First-Line Treatment Algorithm
For macrolide-susceptible or unknown resistance status:
- Azithromycin 500 mg orally on day 1, then 250 mg orally daily for days 2-5 1, 2, 3, 4
- This extended azithromycin regimen achieves 95-99% cure rates and does NOT select for macrolide resistance, unlike single-dose azithromycin 5
Critical pitfall to avoid: Do NOT use azithromycin 1 g as a single dose—while it achieves 85-95% cure rates, it selects for macrolide resistance in 100% of treatment failures 5, 7
Doxycycline should NOT be used as monotherapy for confirmed M. genitalium, as it achieves only 30-40% cure rates 2, 3, 4, 7
Second-Line Treatment (Treatment Failure or Macrolide Resistance)
For macrolide-resistant infections or treatment failure:
- Moxifloxacin 400 mg orally once daily for 7 days (10 days for complicated infections like PID or epididymitis) 3, 4, 6
- Note that moxifloxacin resistance is increasing, making resistance-guided therapy increasingly important 4
Alternative approach when resistance testing unavailable:
- Doxycycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g on day 1, then 500 mg daily for 3 days 6
- This sequential therapy may reduce organism load and decrease resistance selection 4, 6
Third-Line Options for Persistent Infection
- Doxycycline or minocycline 100 mg orally twice daily for 14 days may cure 40-70% of persistent infections 4
- Pristinamycin 1 g orally four times daily for 10 days achieves approximately 75-90% cure rates 3, 4
Patient Instructions and Partner Management
- Patients must abstain from sexual intercourse for 7 days after completing single-dose therapy or until completion of multi-day regimens 1, 2
- All sexual partners require evaluation and treatment, even if asymptomatic, to prevent reinfection 1, 2
- Dispense medications on-site when possible and directly observe the first dose to maximize compliance 8
Follow-Up Requirements
- Patients should return for evaluation if symptoms persist or recur, as this indicates treatment failure requiring resistance testing and alternative therapy 1
- Test-of-cure should be performed 3 weeks after completion of therapy in cases of treatment failure or when compliance is uncertain 6
- Repeat testing at 3-6 months is recommended due to high reinfection rates 1
Important caveat: Testing at less than 3 weeks after therapy completion may yield false-positive results with NAAT due to detection of non-viable organisms 8