What medication is recommended for a 26‑year‑old man presenting with dysuria and a clear urethral discharge?

Treatment for Urethritis with Dysuria and Clear Urethral Discharge

This 26-year-old man should receive empiric dual therapy with ceftriaxone 250 mg intramuscularly as a single dose PLUS either azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days, treating for both gonorrhea and chlamydia simultaneously. 1, 2

Diagnostic Confirmation Before or During Treatment

While empiric treatment should begin immediately, objective confirmation of urethritis strengthens the diagnosis and guides partner management:

• Clear discharge with dysuria suggests nongonococcal urethritis (NGU), but gonorrhea must still be excluded because 20-30% of urethritis cases are gonococcal 1
• Confirm urethritis by demonstrating ≥5 white blood cells per oil immersion field on Gram stain of urethral discharge, OR ≥10 white blood cells per high-power field on first-void urine microscopy, OR positive leukocyte esterase on first-void urine 1, 2, 3
• All patients must be tested for both N. gonorrhoeae and C. trachomatis using nucleic acid amplification testing (NAAT) on urethral swab or first-void urine 1, 2

Why Dual Therapy Is Essential

The CDC guidelines prioritize dual coverage because:

• Chlamydia trachomatis accounts for 23-55% of NGU cases and is the most common pathogen 2, 4, 5
• Gonorrhea cannot be reliably excluded by appearance alone—clear discharge does not rule out N. gonorrhoeae 1, 2
• Mycoplasma genitalium causes 17-33% of NGU and responds better to azithromycin than doxycycline 1, 2, 4
• Treatment must begin immediately without waiting for test results, especially in patients unlikely to return for follow-up 1, 2

Recommended Treatment Regimens

First-Line Dual Therapy (Covers Both Gonorrhea and Chlamydia)

Ceftriaxone 250 mg intramuscularly once 1, 2, 3
PLUS
Azithromycin 1 g orally as a single dose 1, 2
OR
Doxycycline 100 mg orally twice daily for 7 days 1, 2

• Azithromycin offers single-dose convenience and directly observed therapy, improving compliance 1
• Azithromycin is superior for M. genitalium infections, which are increasingly recognized 1, 4
• Doxycycline is equally effective for chlamydia and may be preferred if cost or macrolide resistance is a concern 1

Alternative Regimens (If First-Line Not Tolerated)

If tetracyclines or macrolides are contraindicated:

• Erythromycin base 500 mg orally four times daily for 7 days 1, 2
• Levofloxacin 500 mg orally once daily for 7 days 1
• Ofloxacin 300 mg orally twice daily for 7 days 1, 2

Critical Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen, regardless of symptoms or test results—this is the leading cause of persistent or recurrent urethritis when neglected 1, 2

• Both patient and partners must abstain from sexual intercourse for 7 days after treatment initiation (or until completion of multi-day regimens) and only after symptoms have completely resolved 1, 2
• Expedited partner therapy (giving the patient prescriptions for untested partners) is endorsed by the CDC and approved in many states 6

Follow-Up Strategy

• Patients should return for evaluation ONLY if symptoms persist or recur after completing therapy 1, 2
• Symptoms alone without objective signs (discharge or elevated white blood cells) are insufficient to justify retreatment 1, 2
• Test-of-cure is NOT recommended if the patient received recommended therapy and is asymptomatic 1
• Repeat testing at 3-6 months is recommended because men with chlamydia or gonorrhea have high reinfection rates (20-30%) within 6 months 1, 2

Additional Testing at Diagnosis

All patients diagnosed with sexually transmitted urethritis should receive:

• Syphilis serology 1, 2
• HIV counseling and testing 1, 2

This addresses the increased HIV concentration in semen associated with urethritis and identifies coinfections 6

Management of Persistent or Recurrent Symptoms

If symptoms persist after completing initial therapy:

• Re-confirm urethritis with objective findings (microscopy showing white blood cells or visible discharge) before retreating 1, 2
• Assess for reinfection or noncompliance first—untreated partners are the most common cause 1, 2
• If compliant and reexposure excluded, treat for metronidazole-responsive organisms (Trichomonas vaginalis) and resistant pathogens:
  • Metronidazole 2 g orally as a single dose 1
  • PLUS azithromycin 1 g orally as a single dose (if not used initially) 1
  • Consider moxifloxacin 400 mg orally once daily for 7-14 days for macrolide-resistant M. genitalium 4

Common Pitfalls to Avoid

• Do not treat with single-agent therapy—always cover both gonorrhea and chlamydia empirically 1, 2
• Do not delay treatment waiting for test results in symptomatic patients 1, 2
• Do not assume clear discharge excludes gonorrhea—appearance is unreliable 1, 2
• Do not retreat based on symptoms alone without objective evidence of persistent urethritis 1, 2
• Do not neglect partner treatment—this is the primary cause of treatment failure 1, 2

Complications of Untreated Urethritis

Untreated urethritis leads to:

• Epididymitis in the patient 2, 6, 7
• Reiter's syndrome (reactive arthritis) 2
• Pelvic inflammatory disease in female partners, with risk of infertility and ectopic pregnancy 2, 6
• Increased HIV transmission due to elevated viral load in genital secretions 6