Treatment of Mycoplasma Genitalium Genital Infection
For suspected Mycoplasma genitalium genital infection, treat with doxycycline 100 mg orally twice daily for 7 days as first-line therapy, which provides superior coverage compared to single-dose azithromycin and reduces the risk of macrolide resistance development. 1, 2, 3
Primary Treatment Approach
Doxycycline is the preferred first-line agent because:
- It achieves better cure rates than single-dose azithromycin for M. genitalium and provides dual coverage for other non-gonococcal urethritis pathogens 1
- Single-dose azithromycin 1 g has cure rates below 50% in some studies due to endemic macrolide resistance 4, 5
- Doxycycline 100 mg orally twice daily for 7 days is FDA-approved for nongonococcal urethritis caused by Ureaplasma urealyticum and related organisms 3
- The European Urology guidelines support doxycycline 100 mg twice daily for 7 days as first-line treatment for genital mycoplasma infections 6
Alternative Regimen for Macrolide-Susceptible Cases
If M. genitalium is confirmed by nucleic acid amplification testing and macrolide susceptibility is documented:
- Azithromycin 500 mg orally on day 1, then 250 mg orally daily on days 2-5 achieves 85-95% cure rates in macrolide-susceptible infections 2
- Do not use single-dose azithromycin 1 g, as this regimen drives macrolide resistance and has unacceptably low cure rates 5
Essential Co-Infection Coverage
Always provide empirical coverage for gonorrhea and chlamydia when treating suspected M. genitalium:
- Add ceftriaxone 250 mg intramuscularly as a single dose for gonorrhea coverage 1
- The doxycycline regimen already covers chlamydia 1
- Co-infections are common, and most patients with M. genitalium present with urethritis or cervicitis that may have multiple etiologies 7, 8
Critical Partner Management
All sexual partners within the preceding 60 days must be evaluated and treated simultaneously:
- Partners receive the same treatment regimen regardless of symptoms 1, 2, 6
- Both patient and partners must abstain from sexual intercourse until 7 days after completing therapy 1, 2
- Reinfection rates are extremely high without proper partner management 2
Testing Protocol
Before or concurrent with treatment, obtain:
- Nucleic acid amplification test (NAAT) for N. gonorrhoeae 1
- NAAT for C. trachomatis 1
- Syphilis serology 1
- HIV testing with counseling 1, 2
Note: M. genitalium is very difficult to culture, so NAAT is the only reliable diagnostic method 9, 8
Follow-Up Requirements
- Instruct patients to return if symptoms persist or recur after completing therapy 1, 2
- Consider repeat testing at 3-6 months due to high reinfection rates, particularly if partner treatment compliance is uncertain 1, 2
- Microbiological test-of-cure is not routinely necessary if symptoms resolve and partners are treated 6
- If symptoms persist despite treatment compliance and partner treatment, perform antibiotic sensitivity testing to guide further therapy 6
Special Populations
HIV-infected patients receive identical treatment regimens as HIV-negative patients 7, 6
Common Pitfalls to Avoid
- Never use single-dose azithromycin 1 g for M. genitalium - this drives macrolide resistance and has poor cure rates 5
- Do not treat based on symptoms alone without testing for gonorrhea and chlamydia, as co-infections are common 7, 8
- Do not allow patients to resume sexual activity before completing 7 days of therapy and ensuring partners are treated 1, 2
- Do not assume treatment failure is due to resistance without first confirming partner treatment and excluding reinfection 6