Mycoplasma genitalium Treatment
First-Line Treatment Recommendation
For confirmed M. genitalium infection without known macrolide resistance, use azithromycin 500 mg orally on day 1, followed by 250 mg orally daily on days 2-5, which achieves 93-99% cure rates while minimizing resistance development. 1, 2, 3, 4
Diagnostic Testing Before Treatment
- Always confirm M. genitalium infection with nucleic acid amplification testing (NAAT) before initiating therapy, as empiric treatment without confirmation drives resistance. 1, 3, 4
- Test simultaneously for gonorrhea and chlamydia, as co-infections are common and require different treatment approaches. 1
- Macrolide resistance testing should be performed whenever available to guide initial therapy selection, as resistance mutations strongly predict azithromycin failure. 5, 4
Treatment Algorithm by Resistance Status
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, 3, 4
- Avoid single-dose azithromycin 1g, as this regimen has declining efficacy (dropped from 85.3% before 2009 to 67% after 2009) and increases macrolide resistance development. 6, 7, 5
Macrolide-Resistant Infections (Second-Line)
- Moxifloxacin 400 mg orally once daily for 7 days for uncomplicated infections. 7, 3, 4
- Extend moxifloxacin to 14 days for complicated infections (PID, epididymitis). 3, 4
- Critical caveat: Moxifloxacin efficacy has declined from 100% pre-2010 to 89% post-2010 due to emerging fluoroquinolone resistance. 8, 9
Treatment Failures After Both Azithromycin and Moxifloxacin (Third-Line)
- Doxycycline or minocycline 100 mg orally twice daily for 14 days achieves only 40-70% cure rates but does not induce further resistance. 7, 3, 4
- Pristinamycin 1g orally four times daily for 10 days has approximately 75% cure rate. 7, 3, 4
- Doxycycline monotherapy should never be used as first-line treatment due to poor 30-40% cure rates. 7, 2, 3, 4
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, 2
- All sexual partners require evaluation and treatment, even if asymptomatic, to prevent reinfection. 1, 7, 2
- Dispense medications on-site when possible and directly observe the first dose to maximize compliance. 1
Follow-Up Requirements
- Patients with persistent or recurrent symptoms require re-evaluation, as this indicates treatment failure necessitating resistance testing and alternative therapy. 1, 7
- Repeat testing at 3-6 months is recommended due to high reinfection rates. 1, 7
- Do not perform test-of-cure before 3 weeks after treatment completion, as NAAT may yield false-positive results from detecting non-viable organisms. 1
Key Clinical Pitfalls to Avoid
- Never use empiric azithromycin without confirming M. genitalium infection, as inappropriate macrolide use for other STIs drives resistance in undiagnosed M. genitalium. 5, 4
- The 2022 meta-analysis showed moxifloxacin has superior microbiologic cure compared to azithromycin (OR 2.79), but guidelines still recommend azithromycin first-line for macrolide-susceptible infections to preserve moxifloxacin for resistant cases. 9, 4
- Resistance mutations in 23S rRNA genes strongly predict azithromycin failure, making resistance-guided therapy essential when testing is available. 5, 4
- Multidrug-resistant M. genitalium with both macrolide and fluoroquinolone resistance mutations is emerging, leaving limited treatment options. 5