What is the recommended treatment for Mycoplasma genitalium (M. genitalium) infections?

Treatment of Mycoplasma genitalium Infections

The recommended first-line treatment for Mycoplasma genitalium infections is azithromycin 500 mg on day one, followed by 250 mg on days 2-5 for macrolide-susceptible infections, with a cure rate of 95-99%. 1

Treatment Algorithm

First-line Treatment

• For macrolide-susceptible M. genitalium or when resistance testing is unavailable:
  • Azithromycin 500 mg on day one, followed by 250 mg on days 2-5 (oral) 1, 2
  • This extended regimen has a higher cure rate than the single-dose approach and reduces the risk of developing macrolide resistance

Second-line Treatment

• For macrolide-resistant infections or treatment failures:
  • Moxifloxacin 400 mg once daily for 7 days 1, 2
  • Cure rate approximately 92%, though resistance is increasing 1, 3

Third-line Treatment

• For persistent infection after azithromycin and moxifloxacin:
  • Doxycycline 100 mg twice daily for 14 days (may cure 30-40%) 1, 2
  • Pristinamycin 1 g four times daily for 10 days (cure rate ~75-90%) 1, 2

Resistance Considerations

The treatment landscape for M. genitalium has evolved significantly due to increasing antimicrobial resistance:

• Macrolide resistance has been rising, likely due to widespread use of azithromycin 1g single dose 4, 2
• Single-dose azithromycin (1g) has been associated with development of macrolide resistance in 100% of treatment failures in some studies 5
• Moxifloxacin efficacy has decreased from 100% to 89% since 2010 3
• When available, testing for macrolide resistance mutations should guide therapy 1, 2

Treatment of Complicated Infections

• For complicated M. genitalium infections (PID, epididymitis):
  • Moxifloxacin 400 mg once daily for 14 days 4, 2

Management of Sexual Partners

• Sexual partners should receive the same treatment regimen as the index case 1
• Partners should be evaluated and treated to prevent reinfection 1
• Patients and partners should abstain from sexual intercourse until:
  • 7 days after single-dose therapy, or
  • Until completion of multi-day regimens and resolution of symptoms 1

Follow-up Testing

• A test of cure is recommended 2-4 weeks after completing treatment 1
• This is particularly important given the increasing rates of treatment failure and antimicrobial resistance

Clinical Pitfalls to Avoid

1. Avoid single-dose azithromycin (1g) despite its convenience, as it has been associated with development of macrolide resistance 5
2. Don't use doxycycline as first-line therapy as it has a low cure rate of only 30-40% 4, 2
3. Reserve moxifloxacin as second-line therapy to prevent further development of fluoroquinolone resistance 1
4. Don't forget to test for macrolide resistance when available, as this should guide therapy choices 2
5. Always ensure treatment of sexual partners to prevent reinfection 1

The evidence clearly demonstrates that the extended azithromycin regimen is superior to single-dose therapy for M. genitalium infections, with significantly lower rates of treatment failure and resistance development 5. Moxifloxacin remains effective as second-line therapy but should be used judiciously due to increasing resistance 3.