Treatment for Mycoplasma genitalium
For confirmed Mycoplasma genitalium infection, treat with 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, 4
Diagnostic Testing Before Treatment
- Always confirm M. genitalium infection with nucleic acid amplification testing (NAAT) before initiating therapy 1, 5
- Test simultaneously for gonorrhea and chlamydia, as co-infections are common and require different treatment approaches 1, 5, 2
- If available, perform macrolide resistance testing to guide therapy selection, as macrolide resistance now exceeds 50% in many regions 4, 6, 7
First-Line Treatment Algorithm
For Macrolide-Susceptible or Unknown Resistance Status
- Azithromycin 500 mg orally on day 1, then 250 mg orally once daily for days 2-5 (total dose 1.5 g over 5 days) 1, 2, 3, 4, 6
- This extended regimen achieves 95-99% cure rates and prevents resistance development 1, 3, 8
- Critical pitfall to avoid: Do NOT use single-dose azithromycin 1 g, as cure rates have dropped from 85% to 67% and this regimen selects for macrolide resistance in 100% of treatment failures 1, 8
For Macrolide-Resistant Infections (Second-Line)
- Moxifloxacin 400 mg orally once daily for 7 days for uncomplicated infections 3, 4, 6, 7
- Achieves 92% cure rate in macrolide-resistant cases 7
- Extend to 14 days for complicated infections (pelvic inflammatory disease, epididymitis) 3, 4
For Treatment Failures After Both Azithromycin and Moxifloxacin (Third-Line)
- Doxycycline 100 mg orally twice daily for 14 days may cure 40-70% 4
- Pristinamycin 1 g orally four times daily for 10 days achieves approximately 75% cure rate 4
Alternative Approach When Resistance Testing Unavailable
If macrolide resistance testing is not feasible and treatment has failed:
- Doxycycline 100 mg orally twice daily for 7 days, followed by azithromycin 1 g on day 1, then 500 mg once daily for 3 days 6
- This sequential approach reduces organism load before azithromycin exposure, potentially decreasing resistance selection 4, 6
Critical Treatment Considerations
Do NOT use doxycycline monotherapy for confirmed M. genitalium, as it achieves only 30-40% cure rates and should not be first-line therapy 1, 5, 2, 3, 4, 8
Partner Management and Sexual Activity Restrictions
- Patients must abstain from sexual intercourse for 7 days after completing single-dose therapy or until completion of multi-day regimens 1, 5, 2
- All sexual partners require evaluation and treatment, even if asymptomatic, to prevent reinfection 1, 5, 2
- Dispense medications on-site when possible and directly observe the first dose to maximize compliance 1
Follow-Up Requirements
- Test of cure is recommended 3-6 weeks after treatment completion due to high reinfection rates 1
- Testing at less than 3 weeks may yield false-positive results with NAAT due to detection of non-viable organisms 1
- Patients should return for evaluation if symptoms persist or recur, as this indicates treatment failure requiring resistance testing and alternative therapy 1, 5
- Repeat testing at 3-6 months is recommended due to high reinfection rates 1
Key Clinical Pitfalls to Avoid
- Never use azithromycin 1 g single dose, as this dramatically increases macrolide resistance (100% of treatment failures develop resistance) 8
- Do not treat empirically without testing when NAAT is available, as resistance patterns vary geographically 4, 6
- Do not perform test of cure before 3 weeks, as false positives are common 1
- Ensure partner treatment occurs simultaneously to prevent ping-pong reinfection 1, 5, 2