What is the recommended treatment for Mycoplasma genitalium infections?

Treatment of Mycoplasma genitalium Infections

The recommended first-line treatment for Mycoplasma genitalium is azithromycin 500 mg on day 1, followed by 250 mg daily on days 2-5, which achieves 93-99% cure rates while minimizing macrolide resistance development. 1

Diagnostic Testing Requirements

• All patients with suspected M. genitalium infection should undergo nucleic acid amplification testing (NAAT), as this is the only method to diagnose the infection 2, 3
• Testing for macrolide resistance mutations must be performed when available, as macrolide resistance now exceeds 50% in many regions and dramatically affects treatment outcomes 3, 4
• Concurrent testing for gonorrhea and chlamydia is essential, as co-infections are common 5, 6

First-Line Treatment Strategy

For infections without known macrolide resistance or when resistance testing is unavailable:

• Azithromycin 500 mg orally on day 1, then 250 mg daily on days 2-5 is the preferred regimen, achieving 93-99% cure rates 1
• This extended azithromycin course is superior to the single 1g dose, which has unacceptable failure rates of 16% and promotes resistance development 7, 2

Important caveat: The single-dose azithromycin 1g regimen mentioned in some guidelines 5, 6 is now outdated given evidence of poor efficacy and resistance promotion. The extended 5-day course is strongly preferred 1, 2, 3.

Second-Line Treatment for Macrolide-Resistant Infections

• Moxifloxacin 400 mg orally once daily for 7 days is the recommended second-line therapy for macrolide-resistant infections or treatment failures 2, 3
• Doxycycline-moxifloxacin combination therapy (doxycycline 100 mg twice daily for 7 days followed by moxifloxacin 400 mg daily for 7 days) achieves 92% cure rates in macrolide-resistant cases 4
• Quinolone resistance is increasing, with ParC mutations present in 22% of macrolide-resistant cases, which may compromise moxifloxacin efficacy 4

Alternative Treatment Options

When azithromycin and moxifloxacin have failed:

• Doxycycline 100 mg orally twice daily for 14 days may cure 40-70% of persistent infections, though it should never be used as monotherapy due to only 30-40% cure rates 1, 2, 3
• Pristinamycin 1g four times daily for 10 days achieves approximately 75-90% cure rates as third-line therapy 2, 3

Complicated Infections

• For pelvic inflammatory disease or epididymitis caused by M. genitalium, use moxifloxacin 400 mg once daily for 14 days (extended duration compared to uncomplicated infections) 2, 3

Critical Follow-Up Requirements

• Patients must abstain from sexual intercourse for 7 days after completing therapy 1, 5, 6
• Test of cure should be performed 14-28 days post-treatment, especially given the high rates of treatment failure and emerging resistance 4
• All sexual partners require evaluation and treatment to prevent reinfection 1, 5, 6
• Patients with persistent symptoms after treatment are highly likely to have persistent infection (91% correlation) and require repeat testing and alternative therapy 7

Common Pitfalls to Avoid

• Do not use azithromycin 1g single dose - this outdated regimen has poor efficacy and promotes resistance 7, 2
• Do not use doxycycline as monotherapy - it has only 30-40% cure rates and will lead to treatment failure 1, 2, 3
• Do not skip resistance testing when available - macrolide resistance is now widespread and fundamentally changes treatment approach 3, 4
• Do not assume cure without test of cure - treatment failures are common and asymptomatic persistent infection occurs frequently 7, 4