What is the recommended treatment for Mycoplasma genitalium infection?

Treatment of Mycoplasma Genitalium Infection

For Mycoplasma genitalium infections, the recommended first-line treatment is azithromycin 500 mg on day one, followed by 250 mg on days 2-5 (extended regimen) for macrolide-susceptible infections. 1, 2

Diagnostic Considerations

• Testing for M. genitalium is recommended in patients with urethritis, cervicitis, or related genital tract infections 1
• Concurrent testing for gonorrhea and chlamydia should be performed as co-infections are common 1
• Diagnosis requires nucleic acid amplification testing (NAAT), and should include investigation for macrolide resistance mutations when available 2

Treatment Algorithm

First-Line Treatment

• For uncomplicated M. genitalium without known resistance:
  • Azithromycin 500 mg on day one, then 250 mg on days 2-5 (oral) 1, 2
  • This extended regimen has a cure rate of 85-95% in macrolide-susceptible infections 2
  • Single-dose azithromycin (1g) should be avoided as it may increase development of macrolide resistance 3

Second-Line Treatment (for macrolide-resistant infections)

• Moxifloxacin 400 mg once daily for 7 days 3, 2
• Meta-analysis shows moxifloxacin has better microbiologic cure rates than azithromycin (OR 2.79,95% CI 1.06-7.35) 4
• Note that moxifloxacin efficacy has decreased from 100% to 89% since 2010 due to increasing resistance 5

Third-Line Treatment (after azithromycin and moxifloxacin failure)

• Pristinamycin 1 g four times daily for 10 days (oral) with a cure rate of approximately 75% 3, 2
• Doxycycline or minocycline 100 mg twice daily for 14 days (oral) with a cure rate of 40-70% 3, 2

Treatment Considerations

• Doxycycline alone has a low cure rate of only 30-40% for M. genitalium and should not be used as monotherapy 1, 2
• For complicated infections (PID, epididymitis), moxifloxacin 400 mg once daily for 14 days is recommended 2, 6
• Recent evidence supports resistance-guided therapy (RGT) where treatment is based on resistance testing results:
  • Doxycycline for 7 days followed by 2.5g azithromycin (1g, then 500mg daily for 3 days) for macrolide-susceptible infections (95.7% cure rate) 7
  • Doxycycline for 7 days followed by moxifloxacin for macrolide-resistant infections (92% cure rate) 7

Follow-Up Recommendations

• Patients should abstain from sexual activity during treatment and for 7 days after completion 1, 3
• Sexual partners should be evaluated and treated to prevent reinfection 1, 3
• Patients with persistent or recurrent symptoms should return for evaluation 1, 3
• Test of cure is recommended 3-6 months after treatment, particularly for resistant infections 3

Common Pitfalls and Caveats

• Failing to test for antimicrobial resistance can lead to treatment failure, as macrolide resistance exceeds 50% in many regions 2, 7
• Using single-dose azithromycin (1g) may increase the risk of developing macrolide resistance 3
• Quinolone resistance (including to moxifloxacin) is increasing, with ParC mutations present in approximately 22% of macrolide-resistant cases 7
• Not treating sexual partners can lead to reinfection and persistent symptoms 1, 3