What is the appropriate approach to managing urethral discharge in a male patient, potentially with a history of sexually transmitted infections (STIs) or at high risk for STIs?

Approach to Urethral Discharge in Men

When a man presents with urethral discharge, immediately obtain nucleic acid amplification testing (NAAT) for both N. gonorrhoeae and C. trachomatis on first-void urine or urethral swab, and initiate empiric dual therapy with ceftriaxone 250 mg IM single dose PLUS either azithromycin 1 g orally single dose OR doxycycline 100 mg orally twice daily for 7 days. 1

Initial Diagnostic Evaluation

Confirm Urethritis

Document urethritis objectively through any of the following 2, 1:

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

Critical pitfall: The absence of visible discharge does not exclude urethritis—many chlamydial infections present with minimal or no discharge. 1 Do not defer treatment in symptomatic patients awaiting test results if objective signs are present.

Essential Testing

• NAAT for N. gonorrhoeae and C. trachomatis on first-void urine or urethral swab 1
• Syphilis serology (all patients with sexually transmitted urethritis must be tested) 1, 3
• HIV testing (urethritis facilitates HIV transmission) 1
• Urinalysis on first-void urine to document pyuria 1

Empiric Treatment Regimen

First-Line Therapy

Treat immediately for both gonorrhea and chlamydia 2, 1:

Dual therapy (required):

• Ceftriaxone 250 mg IM as single dose (for gonorrhea) 1
• PLUS either:
  • Azithromycin 1 g orally as single dose 2, 1, 3, OR
  • Doxycycline 100 mg orally twice daily for 7 days 2, 1, 4

Rationale: N. gonorrhoeae (73.5% of cases) and C. trachomatis (22.5% of cases) are the predominant pathogens, with 80% of chlamydial infections coinfected with gonorrhea. 5 Single-dose regimens improve compliance and allow directly observed therapy. 2

Alternative Regimens (if first-line not tolerated) 2

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

Medication should be provided and administered in the clinic whenever possible to ensure compliance. 1

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same empiric dual therapy regimen as the index patient. 1, 6 This is non-negotiable for preventing reinfection and community transmission.

Both patient and all partners must abstain from sexual intercourse for 7 days after treatment initiation. 2, 1, 6 This applies even with single-dose therapy.

Management of Persistent or Recurrent Symptoms

Do Not Retreat Based on Symptoms Alone

Confirm objective signs of urethritis (discharge or pyuria) before retreating—symptoms alone without documentation of urethral inflammation are not sufficient basis for retreatment. 2, 7 This prevents unnecessary antibiotic exposure.

If Objective Signs Persist After Initial Treatment

Step 1: Assess compliance and reexposure 2

• If patient failed to comply with initial regimen OR was reexposed to untreated partner: Retreat with initial dual regimen

Step 2: Test for Trichomonas vaginalis 2, 7

• Obtain first-void urine for T. vaginalis PCR or culture (causes 4% of urethral discharge cases) 7, 5
• Consider semen specimen for PCR or culture (detects additional cases missed by urine alone) 7

Step 3: Empiric treatment for persistent urethritis 1, 7

• Metronidazole 2 g orally single dose (or tinidazole 2 g single dose) PLUS azithromycin 1 g orally single dose if not used initially
• This combination addresses T. vaginalis and Mycoplasma genitalium (common cause of persistent urethritis) 7
• Partners must receive treatment effective against both Chlamydia and Trichomonas regardless of testing results 7

Follow-Up Recommendations

• Patients should return if symptoms persist or recur after completing therapy 2, 1
• Repeat screening at 3 months is recommended for all patients treated for sexually transmitted infections 1
• Test of cure is NOT routinely recommended after completing doxycycline or azithromycin unless symptoms persist or reinfection is suspected 6
• If test of cure is performed, wait at least 3 weeks after completion of therapy 6
• Persistence of symptoms beyond 3 months should prompt evaluation for chronic prostatitis/chronic pelvic pain syndrome 1

Special Considerations

HIV-Infected Patients

HIV-infected patients receive the same treatment regimen as HIV-negative patients. 1 However, partner treatment is particularly important as urethritis facilitates HIV transmission. 1

When Diagnostic Tools Are Unavailable

If Gram stain and microscopy are unavailable, treat empirically for both gonorrhea and chlamydia based on clinical presentation alone. 2 The cost of dual therapy is justified by preventing complications including epididymitis, Reiter's syndrome, and transmission to female partners who risk pelvic inflammatory disease and infertility. 2

Asymptomatic Patients with Positive Testing

Treatment is only indicated if the patient has documented symptoms or objective signs of urethritis—a positive test alone in an asymptomatic patient warrants treatment but with different counseling regarding partner notification. 6