What is the recommended treatment for urethritis caused by Ureaplasma or Mycoplasma?

Treatment of Urethritis Caused by Ureaplasma or Mycoplasma

For urethritis caused by Ureaplasma urealyticum or Mycoplasma genitalium, the recommended first-line treatment is doxycycline 100 mg orally twice daily for 7 days, with azithromycin as an alternative option. 1

Diagnosis Confirmation

Before initiating treatment, it's important to confirm urethritis with objective signs:

• Mucopurulent or purulent urethral discharge
• Gram stain showing ≥5 WBCs per oil immersion field
• Positive leukocyte esterase test on first-void urine
• Microscopic examination of first-void urine showing ≥10 WBCs per high-power field 1

All patients with suspected urethritis should be tested for N. gonorrhoeae and C. trachomatis, as well as other STIs including syphilis and HIV 1.

Treatment Regimens

First-line Treatment Options:

• Doxycycline: 100 mg orally twice daily for 7 days 1, 2

  • Particularly effective for Ureaplasma urealyticum 1
  • FDA-approved specifically for NGU caused by C. trachomatis or U. urealyticum 2

• Azithromycin: 1 g orally in a single dose 1

  • May be more effective for Mycoplasma genitalium infections 1
  • For M. genitalium specifically, an extended regimen of 500 mg on day 1, then 250 mg daily for 4 days may be more effective 1

Alternative Regimens:

• Erythromycin base: 500 mg orally four times daily for 7 days
• Erythromycin ethylsuccinate: 800 mg orally four times daily for 7 days
• Ofloxacin: 300 mg orally twice daily for 7 days
• Levofloxacin: 500 mg orally once daily for 7 days 1

For Persistent Infections:

• For persistent M. genitalium: Moxifloxacin 400 mg orally once daily for 7-14 days 1, 3
• For persistent urethritis: Metronidazole 2 g orally in a single dose plus azithromycin 1 g orally (if not used initially) 1, 3

Treatment Considerations

• Single-dose regimens like azithromycin have the advantage of improved compliance and directly observed therapy 4
• However, using azithromycin as first-line treatment without test of cure for M. genitalium may select for macrolide-resistant strains 3
• For M. genitalium infections, test of cure samples should be collected at least three weeks after treatment 3
• Studies have shown comparable clinical cure rates between azithromycin and doxycycline for empirical treatment of NGU, regardless of the presence of Chlamydia or Ureaplasma 5

Follow-Up and Partner Management

• Patients should abstain from sexual intercourse until 7 days after therapy is initiated and symptoms have resolved 1
• Patients should return for evaluation if symptoms persist or recur after completing therapy 1
• All sexual partners within the preceding 60 days should be referred for evaluation and treatment with the same regimen 1
• Persistent symptoms beyond 3 months should prompt evaluation for chronic prostatitis/chronic pelvic pain syndrome 1

Common Pitfalls

• Treating without confirming diagnosis can lead to unnecessary antibiotic use
• Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not sufficient basis for re-treatment 1
• Neglecting partner treatment can lead to high reinfection rates
• Recent research shows persistent detection of Ureaplasma species after standard treatments is common, even after sequential therapy with doxycycline, azithromycin, and moxifloxacin 6

By following these evidence-based recommendations, clinicians can effectively manage urethritis caused by Ureaplasma or Mycoplasma while minimizing the risk of treatment failure and antibiotic resistance.