Treatment of Mycoplasma genitalium Urinary Tract Infection
For Mycoplasma genitalium UTI, azithromycin 500 mg on day 1 followed by 250 mg daily for 4 days is the recommended first-line treatment, with moxifloxacin 400 mg daily for 7-14 days reserved for macrolide-resistant cases. 1
First-Line Treatment: Extended Azithromycin Regimen
The 2024 European Association of Urology guidelines specifically recommend azithromycin 500 mg orally on day 1 as the primary treatment for Mycoplasma genitalium infection 1. While the guidelines present this as the standard regimen, the evidence strongly suggests the extended 5-day course is superior to single-dose therapy.
Why Extended Azithromycin Over Single-Dose:
- Treatment failure with 1 gram single-dose azithromycin is unacceptably high at 13.9%, with 12% developing macrolide resistance mutations 2
- The 5-day extended regimen reduces treatment failure to only 3.7% when no prior doxycycline has been used 2
- Overall efficacy of 1 gram single-dose has declined from 85.3% pre-2009 to 67% post-2009, approaching 60% in recent studies 3
- The extended regimen is significantly less likely to induce macrolide resistance compared to single-dose therapy 2, 4
Second-Line Treatment: Moxifloxacin
In cases of macrolide resistance, moxifloxacin 400 mg orally daily for 7-14 days should be used 1. This is explicitly stated in the EAU guidelines as the alternative when macrolide resistance is present.
Evidence Supporting Moxifloxacin:
- Moxifloxacin demonstrates superior microbiologic cure compared to azithromycin (OR 2.79,95% CI 1.06-7.35) 5
- Pooled microbial cure rate with moxifloxacin is 96% (95% CI 90%-99%) across multiple studies 6
- Moxifloxacin remains highly active against macrolide-resistant M. genitalium strains 4
Critical Clinical Considerations
Testing Before Treatment:
- Perform nucleic acid amplification testing (NAAT) on first-void urine or urethral swab before initiating empirical treatment 1
- In patients with mild symptoms, delay treatment until NAAT results are available to guide therapy choice 1
- This approach allows for pathogen-directed treatment based on local resistance data 1
Important Caveats:
Resistance is the major concern with M. genitalium treatment. The single-dose 1 gram azithromycin regimen, while still listed in guidelines, is driving worldwide emergence of macrolide resistance 2, 4, 3. The extended 5-day azithromycin regimen significantly reduces this risk while maintaining higher efficacy 2.
Moxifloxacin resistance is emerging. Recent reports document treatment failures with coexistent macrolide and fluoroquinolone resistance mutations 4. However, efficacy remains high at 96% overall, though this has declined from 100% pre-2010 to 89% post-2010 6.
Doxycycline is not recommended as monotherapy for M. genitalium UTI, as its efficacy is relatively poor for this organism 4. The guidelines list doxycycline for non-gonococcal urethritis of unidentified pathogen, but once M. genitalium is confirmed, azithromycin or moxifloxacin should be used 1.
Sexual Partner Management:
Sexual partners should be treated while maintaining patient confidentiality 1. This is a strong recommendation to prevent reinfection and ongoing transmission.
Treatment Algorithm
- Obtain NAAT testing on first-void urine before treatment 1
- If M. genitalium confirmed and no prior macrolide use: Azithromycin 500 mg day 1, then 250 mg daily for 4 days 1, 2
- If macrolide resistance known or suspected: Moxifloxacin 400 mg daily for 7-14 days 1
- If treatment fails after azithromycin: Switch to moxifloxacin 400 mg daily for 7-14 days 1
- Treat all sexual partners concurrently 1