What is the recommended treatment for urethritis?

Treatment of Urethritis

For nongonococcal urethritis, treat with either azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days as first-line therapy. 1, 2, 3

Diagnostic Confirmation Before Treatment

Before initiating treatment, confirm urethritis is present using at least one of the following objective criteria:

• Mucopurulent or purulent urethral discharge on examination 4, 1
• Gram stain of urethral secretions showing ≥5 white blood cells per oil immersion field (≥2 WBCs per oil immersion field in women) 4, 1
• First-void urine demonstrating ≥10 white blood cells per high-power field on microscopic examination 4, 1
• Positive leukocyte esterase test on first-void urine 4, 1

Critical pitfall: Symptoms alone without objective evidence of urethral inflammation are NOT sufficient for diagnosis or treatment 1, 5. Treating based on symptoms alone leads to unnecessary antibiotic exposure and should be avoided except in high-risk patients unlikely to return for follow-up 4.

First-Line Treatment Regimens

Recommended Options (Equal Efficacy)

• Azithromycin 1 g orally as a single dose 1, 3

  • Advantage: Directly observed therapy ensures compliance 1
  • Preferred in pregnancy 1

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

  • Contraindicated in pregnancy 1
  • May have slightly better efficacy against Mycoplasma genitalium, though cure rates remain suboptimal for this organism 6

Both regimens have comparable clinical cure rates of approximately 76-80%, with no significant difference in efficacy 6. The choice between them depends primarily on patient compliance concerns and pregnancy status.

Alternative Regimens (When First-Line Options Cannot Be Used)

• Erythromycin base 500 mg orally four times daily for 7 days 4
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 4
• Ofloxacin 300 mg orally twice daily for 7 days 4
• Levofloxacin 500 mg orally once daily for 7 days 4

Essential Testing

All patients with urethritis must be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis before or at the time of treatment initiation 1. This testing serves multiple purposes:

• Confirms specific pathogen for targeted therapy 4
• Facilitates partner notification 4
• Identifies coinfections requiring additional treatment 7

Partner Management (Non-Negotiable)

• All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen as the index patient 1, 5
• Sexual abstinence is required for 7 days after treatment initiation and until symptoms resolve and partners are adequately treated 1, 5
• Expedited partner treatment (providing prescriptions for partners without examination) is advocated by the CDC and approved in many states 7

Management of Persistent or Recurrent Urethritis

If symptoms persist or recur after initial treatment:

Step 1: Confirm Objective Signs

• Re-document urethritis with objective criteria (discharge or ≥5 PMNs per high-power field) 5
• Do not retreat based on symptoms alone 5

Step 2: Assess Compliance and Re-exposure

• Verify patient completed initial treatment regimen 4, 5
• Determine if re-exposure to untreated partner occurred 4, 5
• If either is present, repeat the initial regimen 4, 5

Step 3: Test for Additional Pathogens

• Perform testing for Trichomonas vaginalis using NAAT or culture on intraurethral swab or first-void urine 4, 5
• Consider testing for tetracycline-resistant Ureaplasma urealyticum 4, 5

Step 4: Treat Persistent Urethritis

If compliance and re-exposure are excluded:

• Metronidazole 2 g orally as a single dose 4, 5
• PLUS Azithromycin 1 g orally as a single dose (if not used initially) 5
• OR Metronidazole 2 g orally as a single dose PLUS Erythromycin base 500 mg orally four times daily for 7 days 4, 5

Alternative: Tinidazole 2 g orally as a single dose can substitute for metronidazole 5

Special Considerations

Pregnancy (Third Trimester)

• Azithromycin 1 g orally as a single dose is the preferred treatment due to safety and effectiveness 1, 8
• Doxycycline and fluoroquinolones are absolutely contraindicated 1
• Erythromycin base 500 mg orally four times daily for 7 days is an alternative 8

HIV-Infected Patients

• Use the same treatment regimens as HIV-negative patients 4, 5
• Urethritis may facilitate HIV transmission, making prompt treatment critical 4

Follow-Up

• Patients should return for evaluation only if symptoms persist or recur after completing therapy 1, 5
• Routine post-treatment testing is NOT recommended in asymptomatic patients 1
• For women whose symptoms do not resolve or recur within 2 weeks, perform urine culture and antimicrobial susceptibility testing 1

Key Clinical Pitfalls to Avoid

• Never treat based on symptoms alone without confirming objective signs of urethritis 1, 5
• Never fail to address untreated partners, as this is the most common cause of treatment failure 5
• Never use empiric treatment in low-risk patients who can return for follow-up 4
• Be aware that Mycoplasma genitalium treatment failure is extremely common (60-70% failure rate) with standard regimens 6, though specific testing and treatment for this organism is not routinely indicated initially 4