Treatment for Mycoplasma genitalium Infections
For confirmed M. genitalium infection without known macrolide resistance, treat with azithromycin 500 mg orally on day 1, followed by 250 mg daily on days 2-5, which achieves 93-99% cure rates while minimizing resistance development. 1
Diagnostic Testing Before Treatment
- Perform nucleic acid amplification testing (NAAT) to confirm M. genitalium infection before initiating therapy 1
- Test simultaneously for gonorrhea and chlamydia, as co-infections are common and require different treatment approaches 1, 2
- Testing for macrolide resistance mutations should be performed when available, as this guides therapy selection 3
First-Line Treatment Algorithm
For macrolide-susceptible or unknown resistance status:
- Azithromycin 500 mg orally on day 1, then 250 mg orally daily on days 2-5 achieves 95-99% cure rates 1, 4
- This extended dosing regimen is superior to single-dose azithromycin 1g, which has only 84-91% cure rates and promotes macrolide resistance development in 100% of treatment failures 5, 6
Critical pitfall to avoid: Do not use azithromycin 1g single dose as first-line therapy, despite it appearing in some older recommendations 2. This regimen selects for macrolide resistance in all treatment failures 5 and has significantly lower cure rates than the extended 5-day regimen 1, 3.
Second-Line Treatment
For macrolide-resistant infections or treatment failures:
- Moxifloxacin 400 mg orally once daily for 7 days for uncomplicated infections 3, 7
- Moxifloxacin 400 mg orally once daily for 14 days for complicated infections (PID, epididymitis) 3, 7
- Moxifloxacin historically achieved 96-100% cure rates, but efficacy has declined to 89% since 2010 due to emerging fluoroquinolone resistance 8
Third-Line Options for Persistent Infection
- Doxycycline or minocycline 100 mg twice daily for 14 days may cure 40-70% of persistent infections 3
- Pristinamycin 1g four times daily for 10 days has approximately 75% cure rate 3
Important caveat: Doxycycline 100 mg twice daily for 7 days has only 30-40% cure rate and should never be used as monotherapy for confirmed M. genitalium 1, 4, 3. However, it may be considered as empiric therapy when testing is unavailable and chlamydia/gonorrhea are also suspected 1.
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, 4
- All sexual partners require evaluation and treatment, even if asymptomatic, to prevent reinfection 1, 4
- Dispense medications on-site when possible and directly observe the first dose to maximize compliance 1
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, 2
- Repeat testing at 3-6 months is recommended due to high reinfection rates 1
- Testing at less than 3 weeks after therapy completion may yield false-positive results with NAAT due to detection of non-viable organisms 1
- Persistent symptoms after treatment strongly correlate with persistent infection (91% vs 17% in those cured), making symptom assessment a critical indicator for treatment failure 6
Resistance Considerations
The landscape of M. genitalium treatment has shifted dramatically due to antimicrobial resistance. Macrolide resistance has increased from 0% in 2006-2007 to 18% by 2011 in some populations 5, and moxifloxacin resistance is also emerging 3, 8. This underscores the importance of resistance-guided therapy when testing is available and the need for test-of-cure in all treated patients 3.