What is the treatment approach for urethritis in men?

Treatment of Urethritis in Men

First-line treatment for urethritis in men is either azithromycin 1g orally as a single dose OR doxycycline 100mg orally twice daily for 7 days, with azithromycin preferred when compliance is uncertain or when Mycoplasma genitalium is suspected. 1, 2

Confirm the Diagnosis Before Treatment

Before initiating therapy, urethritis must be documented by at least one of the following criteria: 3, 1, 2

• Mucopurulent or purulent urethral discharge on examination
• Gram stain of urethral secretions showing ≥5 white blood cells per oil immersion field (preferred rapid diagnostic test)
• Positive leukocyte esterase test on first-void urine
• Microscopic examination of first-void urine showing ≥10 white blood cells per high-power field

All patients with confirmed or suspected urethritis must be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests, which are more sensitive than culture. 3, 1, 2

First-Line Treatment Regimens

The Centers for Disease Control and Prevention recommends two equally effective first-line options: 3, 1, 2

Option 1: Azithromycin

• Azithromycin 1g orally as a single dose 3, 1, 2
• Advantages: Single-dose therapy ensures compliance and allows directly observed treatment 3
• Particularly effective against Mycoplasma genitalium, which may account for cases not responding to doxycycline 3, 1
• FDA-approved for urethritis due to Chlamydia trachomatis or Neisseria gonorrhoeae 4

Option 2: Doxycycline

• Doxycycline 100mg orally twice daily for 7 days 3, 1, 2
• Highly effective for chlamydial urethritis 3, 1
• Requires patient compliance with multi-day regimen 3

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

If azithromycin and doxycycline are contraindicated or not tolerated: 3

• Erythromycin base 500mg orally four times daily for 7 days 3
• Erythromycin ethylsuccinate 800mg orally four times daily for 7 days 3
• Ofloxacin 300mg orally twice daily for 7 days 3
• Levofloxacin 500mg orally once daily for 7 days 3

Empiric Treatment Without Confirmed Urethritis

Empiric treatment without documentation of urethritis should only be given to high-risk patients unlikely to return for follow-up, and must include coverage for both gonorrhea and chlamydia. 3, 1, 2 This approach accepts the cost of overtreatment to prevent complications in patients who will be lost to follow-up.

Partner Management is Mandatory

All sexual partners within the preceding 60 days must be referred for evaluation and treatment, regardless of whether a specific pathogen is identified in the index patient. 3, 1, 2 Partners should receive treatment effective against chlamydia even if testing is negative or pending. 1, 2

Both patient and partners must abstain from sexual intercourse until 7 days after therapy is initiated AND symptoms have completely resolved. 3, 1

Management of Persistent or Recurrent Urethritis

If symptoms persist or recur after initial treatment: 3, 1, 2

1. Re-confirm objective signs of urethritis before retreating—symptoms alone without documented inflammation are insufficient for additional antimicrobial therapy 3

2. Rule out non-compliance with initial treatment or re-exposure to untreated partners 3, 1

3. If urethritis is confirmed and compliance/partner treatment verified, treat with: 1, 2

   • Metronidazole 2g orally as a single dose OR tinidazole 2g orally as a single dose
   • PLUS azithromycin 1g orally as a single dose (if not used for initial episode)

4. Consider testing for Trichomonas vaginalis, which can cause persistent urethritis 3

Follow-Up Recommendations

• Patients should return for evaluation only if symptoms persist or recur after treatment completion 3, 1, 2
• Test-of-cure is NOT recommended for asymptomatic patients who received recommended treatment 1, 2
• Consider repeat testing 3-6 months after treatment due to high reinfection rates 1, 2
• Symptoms persisting beyond 3 months without objective urethritis should prompt evaluation for chronic prostatitis/chronic pelvic pain syndrome 3

Critical Pitfalls to Avoid

Do not retreat based on symptoms alone—extending antimicrobial duration without documented urethritis has not been shown to be beneficial. 3 Many men will have persistent mild symptoms without objective inflammation, and additional antibiotics are not indicated in this scenario.

All patients diagnosed with a new sexually transmitted infection should receive testing for other STDs, including syphilis and HIV. 3, 1 Antimicrobials used for urethritis may mask or delay symptoms of incubating syphilis, so serologic testing at diagnosis is essential. 3