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 (extended regimen), which achieves 93-99% cure rates while minimizing macrolide resistance development. 1
Diagnostic Testing Before Treatment
- Confirm M. genitalium infection using nucleic acid amplification testing (NAAT) before initiating therapy, rather than treating empirically 1
- Test simultaneously for gonorrhea and chlamydia, as co-infections are common and require different treatment approaches 1, 2
- If available, perform macrolide resistance testing to guide therapy selection 3
Critical caveat: The 2010 CDC guidelines 4 predate our understanding of macrolide resistance and recommend azithromycin 1 g single dose, but this approach is now outdated and should be avoided.
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 1, 3
- This extended regimen achieves 95-99% cure rates 1 and causes resistance in only 2.6% of cases 5
Why the extended regimen is superior:
- Azithromycin 1 g single dose has a 13.9% treatment failure rate and causes macrolide resistance in 12% of patients 6
- The extended 5-day regimen reduces treatment failure to 3.7% 6
- Single-dose azithromycin selected for resistance in 100% of treatment failures in one Swedish study 7
Second-Line Treatment for Macrolide-Resistant Infections
For confirmed macrolide resistance or treatment failure:
- Moxifloxacin 400 mg orally once daily for 7-10 days 3
- Cure rate is 92.2% for macrolide-resistant infections 5
- However, moxifloxacin efficacy has declined from 100% pre-2010 to 89% post-2010 due to emerging fluoroquinolone resistance 8
Role of Doxycycline
- Doxycycline 100 mg orally twice daily for 7 days has only 30-40% cure rate as monotherapy 2, 3
- However, doxycycline as initial therapy before azithromycin reduces bacterial load by 2.60 log10 and improves subsequent cure rates to >92% 5
- Doxycycline does not induce resistance, making it useful as a "priming" agent 3
Patient Instructions and Partner Management
- 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
- Dispense medications on-site when possible and directly observe the first dose to maximize compliance 1
Follow-Up Requirements
- Patients should return if symptoms persist or recur after treatment, indicating treatment failure requiring resistance testing 1
- Test of cure should be performed 14-90 days after treatment completion 5
- Avoid testing before 3 weeks post-treatment, as NAAT may detect non-viable organisms and yield false-positive results 1
- Repeat testing at 3-6 months is recommended due to high reinfection rates 1
- Test for other STIs including syphilis and HIV 9
Complicated Infections
For pelvic inflammatory disease or epididymitis caused by M. genitalium:
- Moxifloxacin 400 mg orally once daily for 14 days 3