Treatment of Mycoplasma genitalium Infection
Azithromycin 500 mg orally on day 1, followed by 250 mg daily on days 2-5 is the recommended first-line treatment for Mycoplasma genitalium infection. 1
Diagnostic Testing Before Treatment
- Test for macrolide resistance mutations whenever possible before initiating therapy, as this critically guides treatment selection and predicts treatment success 2
- Always test for co-infections with gonorrhea and chlamydia, as these frequently occur together with M. genitalium 1, 3
- Diagnosis requires nucleic acid amplification testing (NAAT); culture is not clinically available 4
First-Line Treatment Regimen
For infections without known macrolide resistance:
- Azithromycin 500 mg orally on day 1, then 250 mg orally on days 2-5 (total 1.5 g over 5 days) 4, 2
- This extended regimen achieves 85-95% cure rates in macrolide-susceptible infections 4, 2
- The extended course is superior to single-dose azithromycin 1 g, which has unacceptable failure rates of 16% even without reinfection risk 5
Critical caveat: Single-dose azithromycin 1 g is no longer recommended as optimal therapy despite older CDC guidance, as it drives macrolide resistance and has lower cure rates 5, 2
Second-Line Treatment
For macrolide-resistant infections or azithromycin treatment failure:
- Moxifloxacin 400 mg orally once daily for 7 days for uncomplicated infections 4, 2
- Moxifloxacin achieves 96% overall cure rates, though efficacy has declined from 100% pre-2010 to 89% post-2010 due to emerging fluoroquinolone resistance 6
- Extend moxifloxacin to 14 days for complicated infections (PID, epididymitis) 4, 2
- Moxifloxacin effectively eradicates persistent infection after azithromycin failure 5
Third-Line Options for Multidrug-Resistant Infections
When both azithromycin and moxifloxacin fail:
- Doxycycline 100 mg orally twice daily for 14 days may cure 40-70% of persistent infections 2
- Pristinamycin 1 g orally four times daily for 10 days achieves approximately 75% cure rates 2
- Note that doxycycline monotherapy has only 30-40% cure rates and should not be used as first-line therapy 1, 4
Follow-Up Management
- Patients must abstain from sexual intercourse for 7 days after completing therapy 1, 3
- All sexual partners require evaluation and treatment to prevent reinfection 1, 3
- Patients with persistent symptoms after treatment should return for re-evaluation 1, 3
- Persistent symptoms strongly correlate with treatment failure: 91% of patients with persistent M. genitalium had ongoing symptoms versus only 17% of those successfully treated 5
Critical Pitfalls to Avoid
- Do not use single-dose azithromycin 1 g, as this drives macrolide resistance and has suboptimal cure rates 5, 2
- Avoid repeated courses of the same antibiotic for persistent infections 3
- Do not skip resistance testing when available, as macrolide resistance prevalence is increasing and dramatically affects treatment outcomes 2, 7
- Be aware that asymptomatic infections are common and contribute to ongoing transmission if partners are not treated 3, 4
- Recognize that multidrug-resistant M. genitalium with both macrolide and fluoroquinolone resistance mutations is emerging 7