A 22-year-old male presents with dysuria after sexual intercourse with a new partner, without fever, increased urinary frequency, or urgency, and without symptoms of urethritis, what is the differential diagnosis and treatment?

Differential Diagnosis and Treatment of Dysuria in a Young Male After New Sexual Contact

This 22-year-old male most likely has non-gonococcal urethritis (NGU) and should be treated empirically with azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days, combined with ceftriaxone 250 mg IM as a single dose to cover both chlamydia and gonorrhea. 1, 2, 3

Differential Diagnosis

The primary diagnostic considerations in this clinical scenario include:

Most Likely: Sexually Transmitted Urethritis

• Chlamydia trachomatis is the most common cause of NGU, accounting for 30-40% of cases 1, 4
• Neisseria gonorrhoeae must be considered given the sexual exposure, even without classic purulent discharge 1, 4
• Mycoplasma genitalium is an increasingly recognized pathogen that may respond better to azithromycin than doxycycline 1, 5
• Ureaplasma urealyticum (not U. parvum) can cause NGU 1, 4
• Trichomonas vaginalis should be considered, particularly if symptoms persist after initial treatment 1, 4

Less Common Considerations

• Herpes simplex virus can cause dysuria, though typically with visible lesions 6
• Adenovirus is a rare cause of urethritis 6
• Non-infectious causes including chemical irritants or trauma are possible but less likely given the temporal relationship to sexual contact 5

Diagnostic Approach

Clinical Criteria for Urethritis Diagnosis

A diagnosis of urethritis can be made if at least one of the following is present 4, 6:

• Mucopurulent or purulent urethral discharge on examination
• Gram stain showing ≥2 white blood cells per oil immersion field in urethral secretions
• First-void urine showing ≥10 white blood cells per high-power field
• Positive leukocyte esterase test on first-void urine

Essential Testing

• Urinalysis on first-void urine to document pyuria 5, 4
• Nucleic acid amplification testing (NAAT) for both N. gonorrhoeae and C. trachomatis on first-void urine or urethral swab 1, 4
• Consider M. genitalium testing if initial tests are negative and symptoms persist 5, 4
• Syphilis serology and HIV testing should be offered to all patients with sexually transmitted urethritis 1

Important Clinical Caveat

The absence of visible urethral discharge does NOT exclude urethritis—many chlamydial infections present with minimal or absent discharge 1, 6. The symptom of dysuria alone has high specificity (>90%) for laboratory-confirmed urethritis when both discharge and dysuria are present 7.

Empiric Treatment Recommendations

First-Line Regimen

Treat empirically before test results are available 1, 4:

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

This dual therapy covers both gonococcal and non-gonococcal urethritis. Single-dose azithromycin offers the advantage of directly observed therapy and improved compliance 1.

Alternative Regimens (if patient cannot tolerate first-line)

• Erythromycin base 500 mg orally four times daily for 7 days 1
• Ofloxacin 300 mg orally twice daily for 7 days (only if local gonorrhea resistance <10% and no recent fluoroquinolone use) 1
• Levofloxacin 500 mg orally once daily for 7 days 1

Critical Treatment Principles

• Medication should ideally be provided and administered in the clinic to ensure compliance 1
• Treatment should be initiated as soon as possible after diagnosis, even before test results return 1, 2
• Adjust therapy once culture/NAAT results are available 2, 3

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated 1:

• Partners should receive the same empiric treatment regimen as the index patient 8
• If last sexual contact was >60 days ago, treat the most recent partner 1
• Both patient and partners must abstain from sexual intercourse for 7 days after treatment initiation and until symptoms resolve and partners are adequately treated 1, 4

Management of Persistent or Recurrent Symptoms

If Symptoms Persist After Initial Treatment

Confirm objective signs of urethritis before re-treating—symptoms alone without documented urethral inflammation are insufficient for re-treatment 1, 8:

1. First, rule out non-compliance or partner re-exposure 8

   • If either is present, repeat the initial regimen 1, 8

2. If compliant and no re-exposure, perform additional testing 8:

   • T. vaginalis culture or NAAT on intraurethral swab or first-void urine 1, 8
   • Consider testing for tetracycline-resistant U. urealyticum 1, 8

3. Recommended regimen for persistent urethritis 1, 8:

   • Metronidazole 2 g orally as a single dose OR Tinidazole 2 g orally as a single dose
   • PLUS Azithromycin 1 g orally as a single dose (if not used initially)

Important Pitfall to Avoid

Do NOT re-treat based on symptoms alone without documenting objective signs of urethritis (discharge or pyuria) 1, 8. Approximately 50% of men with chronic pelvic pain syndrome have urethral inflammation without identifiable pathogens 1.

Follow-Up Recommendations

• Patients should return if symptoms persist or recur after completing therapy 1
• Test-of-cure is NOT routinely recommended <3 weeks after treatment due to risk of false-positive results 4
• Repeat screening at 3 months is recommended for all patients treated for sexually transmitted infections 4
• Persistence of symptoms beyond 3 months should prompt evaluation for chronic prostatitis/chronic pelvic pain syndrome 1, 8

Special Considerations

HIV Status

• HIV-infected patients should receive the same treatment regimen as HIV-negative patients 1
• Urethritis may facilitate HIV transmission, making partner treatment particularly important 1, 6

Syphilis Co-infection

Azithromycin at standard urethritis doses will NOT adequately treat incubating syphilis 2. All patients must have syphilis serology performed at diagnosis, with appropriate follow-up if positive 1.