What is the recommended treatment for Mycoplasma genitalium infections?

Treatment for Mycoplasma genitalium Infections

For confirmed M. genitalium infections, use azithromycin 500 mg orally on day 1, followed by 250 mg daily for days 2-5, which achieves 93-99% cure rates while minimizing macrolide resistance development. 1

Diagnostic Testing Before Treatment

• Perform nucleic acid amplification testing (NAAT) to confirm M. genitalium infection before initiating therapy, as diagnosis cannot be made clinically or through culture. 1
• Test simultaneously for gonorrhea and chlamydia, since co-infections are common and require different treatment approaches. 1, 2
• When available, test for macrolide resistance mutations to guide therapy selection, as resistance rates have increased dramatically (from 0% in 2006-2007 to 18% by 2011 in some populations). 3, 4

First-Line Treatment Algorithm

For macrolide-susceptible or unknown resistance status:

• Azithromycin 500 mg orally on day 1, then 250 mg orally daily for days 2-5 achieves 95-99% cure rates. 1, 5
• This extended 5-day regimen is superior to the single 1 g dose, which has only 84-91% cure rates and causes macrolide resistance development in 100% of treatment failures. 4, 6

Critical pitfall to avoid: Do not use azithromycin 1 g single dose as first-line therapy, despite some older guidelines suggesting this approach. 2 The single-dose regimen selects for macrolide-resistant strains in all treatment failures, whereas the extended regimen does not cause resistance development. 4

Second-Line Treatment

For macrolide-resistant infections or treatment failures:

• Moxifloxacin 400 mg orally once daily for 7-10 days for uncomplicated infections. 3, 7
• Extend moxifloxacin to 14 days for complicated infections (pelvic inflammatory disease, epididymitis). 3, 7
• Moxifloxacin historically achieved 96-100% cure rates, but efficacy has declined to 89% since 2010 due to emerging fluoroquinolone resistance. 8

Third-Line Options for Persistent Infection

• Doxycycline 100 mg orally twice daily for 14 days may cure 30-70% of persistent infections, though it should never be used as first-line therapy due to only 30-40% cure rates. 1, 3, 4
• Pristinamycin 1 g orally four times daily for 10 days achieves approximately 75-90% cure rates in treatment-refractory cases. 3, 7

Patient Management Requirements

• Patients must abstain from sexual intercourse for 7 days after completing single-dose therapy or until completion of multi-day regimens. 1, 5
• All sexual partners require evaluation and treatment, even if asymptomatic, to prevent reinfection. 1, 2
• Dispense medications on-site when possible and directly observe the first dose to maximize compliance. 1

Follow-Up Protocol

• Patients should return for evaluation if symptoms persist or recur, as this indicates treatment failure requiring resistance testing and alternative therapy. 1, 2
• Repeat testing at 3-6 months is recommended due to high reinfection rates. 1
• Avoid testing earlier than 3 weeks after therapy completion, as NAAT may yield false-positive results from detection of non-viable organisms. 1
• Patients with persistent M. genitalium after treatment are significantly more likely to have persistent symptoms (91%) compared to those successfully treated (17%). 6

Important caveat: Doxycycline achieves only 30-40% cure rates and should not be used as monotherapy for confirmed M. genitalium, though it may be considered as empiric therapy when testing is unavailable and chlamydia/gonorrhea are also suspected. 1, 3