What is the treatment for urethritis?

Treatment of Urethritis

For confirmed urethritis, initiate empiric dual therapy immediately with Ceftriaxone 250-500 mg IM single dose PLUS Doxycycline 100 mg orally twice daily for 7 days to cover both gonorrhea and chlamydia. 1

Confirming the Diagnosis Before Treatment

Before initiating therapy, document urethritis using at least one of these objective criteria: 2, 1

• Mucopurulent or purulent urethral discharge (visible on examination) 2
• Gram stain of urethral secretions showing ≥5 WBCs per oil immersion field (preferred rapid diagnostic test) 2
• Positive leukocyte esterase test on first-void urine 2
• Microscopic examination of first-void urine showing ≥10 WBCs per high-power field 2

If none of these criteria are present, defer treatment and test for N. gonorrhoeae and C. trachomatis using nucleic acid amplification tests, then follow closely. 2, 3

When to Treat Empirically Without Confirmed Urethritis

The only exception: Treat empirically without documentation of urethritis for high-risk patients unlikely to return for follow-up (e.g., adolescents with multiple partners). 2, 3 These patients should receive dual coverage for both gonorrhea and chlamydia. 2

First-Line Treatment Regimens

Dual Therapy (Preferred for Empiric Treatment)

Ceftriaxone 250-500 mg IM single dose PLUS Doxycycline 100 mg orally twice daily for 7 days 1

This dual regimen is essential because: 1

• Most sexually transmitted urethritis in men under 35 is caused by C. trachomatis or N. gonorrhoeae 1
• Co-infection with both pathogens is common 1
• Delaying treatment increases risk of complications (epididymitis) and ongoing transmission 1

Alternative Regimens for Nongonococcal Urethritis (If Gonorrhea Ruled Out)

Recommended: 2, 1

• Azithromycin 1 g orally single dose (advantage: single-dose ensures compliance, particularly effective against M. genitalium) 2, 4
• OR Doxycycline 100 mg orally twice daily for 7 days (highly effective for chlamydial urethritis) 2

Alternative regimens if first-line options contraindicated: 2

• Erythromycin base 500 mg orally four times daily for 7 days 2
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 2
• Ofloxacin 300 mg orally twice daily for 7 days 2
• Levofloxacin 500 mg orally once daily for 7 days 2

Critical Management Steps

Testing Requirements

• All patients with confirmed or suspected urethritis must be tested for both gonorrhea and chlamydia using nucleic acid amplification tests 2, 1
• Perform HIV and syphilis testing as part of comprehensive STI screening 1, 3
• Testing for chlamydia is strongly recommended because specific diagnosis enhances partner notification and compliance 2

Partner Management

• Refer all sexual partners within the preceding 60 days for evaluation and treatment 2, 1
• Partners should receive treatment effective against chlamydia regardless of whether a specific pathogen is identified in the index patient 1, 3
• Both patient and all partners must abstain from sexual intercourse until 7 days after therapy initiation AND symptom resolution 2, 1

Follow-Up

• Patients should return only if symptoms persist or recur after completing therapy 2
• Symptoms alone without objective signs of urethritis are NOT sufficient basis for re-treatment 2
• Consider repeat testing 3-6 months after treatment due to high reinfection rates 3
• Test-of-cure is not recommended for asymptomatic patients who received recommended treatment 5

Management of Persistent or Recurrent Urethritis

Objective signs of urethritis must be present before initiating additional antimicrobial therapy. 2

Re-treatment Algorithm:

1. If patient did not comply with initial regimen OR was re-exposed to untreated partner: Re-treat with the initial regimen 2

2. If patient was compliant and re-exposure excluded: 2

   • Perform culture for T. vaginalis 2
   • Consider tetracycline-resistant U. urealyticum 2
   • Recommended regimen for persistent/recurrent urethritis: 2
     • Metronidazole 2 g orally single dose PLUS
     • Erythromycin base 500 mg orally four times daily for 7 days OR Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days

3. If symptoms persist beyond 3 months: Consider chronic prostatitis/chronic pelvic pain syndrome 2

Common Pitfalls to Avoid

• Never treat for gonorrhea alone without chlamydia coverage – co-infection is extremely common 1
• Do not treat based on symptoms alone without objective evidence of urethritis unless patient meets high-risk criteria for empiric treatment 3
• Do not forget that antimicrobials used for urethritis may mask or delay symptoms of incubating syphilis – all patients with sexually transmitted urethritis must have serologic testing for syphilis 4
• Failure to improve within 3 days requires diagnostic re-evaluation 1
• Do not rely on semen analysis to diagnose urethritis – use proper urethral testing criteria 5

Special Considerations

HIV-Positive Patients

Patients with urethritis who are also HIV-positive should receive the same treatment regimen as HIV-negative patients. 2, 1 Gonococcal and chlamydial urethritis may facilitate HIV transmission. 2

Medication Provision

To improve compliance, medication should ideally be provided directly in the clinic or healthcare provider's office, allowing for directly observed therapy with single-dose regimens. 2