What is the recommended treatment for Mycoplasma genitalium infection?

Treatment for Mycoplasma genitalium Infection

For confirmed M. genitalium infection without known macrolide resistance, treat with azithromycin 500 mg orally on day 1, followed by 250 mg daily on days 2-5, which achieves 93-99% cure rates while minimizing resistance development. 1

Diagnostic Testing Before Treatment

• Confirm M. genitalium infection using nucleic acid amplification testing (NAAT) before initiating therapy 1
• Test simultaneously for gonorrhea and chlamydia, as co-infections are common and require different treatment approaches 1, 2
• When available, perform macrolide resistance testing to guide therapy selection, as macrolide resistance now exceeds 50% in many regions 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, 3
• This extended azithromycin regimen is superior to single-dose azithromycin 1g, which has lower efficacy and selects for macrolide resistance 5

Critical pitfall to avoid: Single-dose azithromycin 1g should NOT be used as it develops macrolide resistance in 100% of treatment failures 5

Second-Line Treatment for Macrolide-Resistant Infections

• Moxifloxacin 400 mg orally once daily for 7 days (10 days for complicated infections) 3, 6
• Doxycycline-moxifloxacin combination achieves 92% cure rates for macrolide-resistant cases 4
• Warning: Quinolone resistance is increasing, with ParC mutations present in 22% of macrolide-resistant cases 4

Alternative Regimen for Macrolide-Susceptible Infections

• Doxycycline 100 mg orally twice daily for 7 days followed by azithromycin 2.5g (1g on day 1, then 500mg daily for 3 days) achieves 95.4-95.7% cure rates 4
• Doxycycline monotherapy has only 30-40% cure rate and should never be used alone for confirmed M. genitalium 1, 3

Third-Line Options for Persistent Infections

• Doxycycline or minocycline 100 mg orally twice daily for 14 days may cure 40-70% 3
• Pristinamycin 1g orally four times daily for 10 days has approximately 75-90% cure rate 3, 6

Complicated Infections (PID, Epididymitis)

• Moxifloxacin 400 mg orally once daily for 14 days 3, 6

Patient Instructions and Partner Management

• Patients must abstain from sexual intercourse for 7 days after completing single-dose therapy or until completion of multi-day regimens 1, 2
• 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 Requirements

• Patients should return for evaluation if symptoms persist or recur, indicating treatment failure requiring resistance testing and alternative therapy 1, 2
• Test of cure at 3-6 months is recommended due to high reinfection rates 1
• Critical timing: Testing at less than 3 weeks after therapy completion may yield false-positive results with NAAT due to detection of non-viable organisms 1
• De novo macrolide resistance develops in 4.6% of cases, emphasizing the importance of test of cure 4