What is the recommended treatment for urethritis (inflammation of the urethra)?

Treatment of Urethritis

The recommended first-line treatment for urethritis is either azithromycin 1g orally in a single dose or doxycycline 100mg orally twice daily for 7 days. 1, 2

Diagnosis

Before initiating treatment, it's essential to confirm urethritis with at least one of the following:

• Mucopurulent or purulent urethral discharge 1, 2
• Gram stain of urethral secretions showing ≥5 WBC per oil immersion field 1
• Positive leukocyte esterase test on first-void urine 2
• Microscopic examination of first-void urine showing ≥10 WBC per high-power field 1, 2

All patients with confirmed or suspected urethritis should be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis to guide appropriate treatment 1, 2.

Treatment Algorithm

First-Line Treatment Options:

• Azithromycin 1g orally in a single dose 1, 3
  • Advantages: Single-dose regimen improves compliance and allows for directly observed therapy 1
  • Particularly effective against Mycoplasma genitalium 2, 4

OR

• Doxycycline 100mg orally twice daily for 7 days 1, 5
  • Highly effective for chlamydial urethritis 2

Alternative Regimens (when first-line options cannot be used):

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

Management Considerations

Testing Before Treatment

• Ideally, delay treatment until test results are available to guide therapy, especially in patients with mild symptoms 1
• Perform a urethral swab culture before initiating treatment in patients with a positive NAAT for gonorrhea to assess antimicrobial resistance 1

Empiric Treatment

• Empiric treatment without documentation of urethritis is recommended only for high-risk patients unlikely to return for follow-up 1, 2
• Such patients should receive treatment for both gonorrhea and chlamydia 1

Partner Management

• All sexual partners within the preceding 60 days should be referred for evaluation and treatment 1, 2
• Partners should receive treatment effective against chlamydia regardless of whether a specific etiology is identified in the index patient 2

Management of Persistent or Recurrent Urethritis

If symptoms persist or recur after treatment:

1. Confirm objective signs of urethritis before initiating further antimicrobial therapy 1
2. Rule out non-compliance with initial treatment or re-exposure to untreated partner 1
3. If patient was compliant and re-exposure can be excluded, recommended treatment is:
   • Metronidazole 2g orally in a single dose PLUS 1, 2
   • Erythromycin base 500mg orally four times a day for 7 days OR erythromycin ethylsuccinate 800mg orally four times a day for 7 days 1

Follow-Up Recommendations

• Patients should return for evaluation if symptoms persist or recur after treatment 1
• Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not sufficient basis for re-treatment 1
• Patients should abstain from sexual intercourse until 7 days after therapy is initiated, symptoms have resolved, and partners have been adequately treated 1, 6
• Consider repeat testing 3-6 months after treatment due to high rate of reinfection 2

Special Considerations

Antimicrobial Resistance

• Recent studies have shown increasing rates of macrolide resistance in M. genitalium, which may affect treatment success with azithromycin 7
• The European Association of Urology recommends using pathogen-directed treatment based on local resistance data 1

HIV Infection

• Patients with urethritis who are also HIV-positive should receive the same treatment regimen as HIV-negative patients 1
• Urethritis may facilitate HIV transmission, making prompt and effective treatment particularly important 8