What is the recommended treatment for a 30-year-old male with recurrent urethritis (inflammation of the urethra), presenting with symptoms of urethral tenderness, burning sensation, and a history of two prior urinary tract infections (UTIs)?

Recommended Treatment for Recurrent Urethritis in a 30-Year-Old Male

This patient requires objective documentation of urethritis before initiating treatment, followed by empiric therapy with azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days, targeting both Chlamydia trachomatis and Mycoplasma genitalium. 1

Diagnostic Confirmation Required First

Before treating, urethritis must be objectively documented using at least one of the following criteria: 1

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

Critical pitfall to avoid: Symptoms alone (burning, tenderness) without objective evidence are NOT sufficient for diagnosis or treatment. 1, 2 The CDC explicitly states this to prevent unnecessary antibiotic use and resistance development.

Testing Strategy

All patients with confirmed urethritis should be tested for: 1

• N. gonorrhoeae (using NAAT)
• C. trachomatis (using NAAT)
• Consider M. genitalium testing if available, especially given recurrent symptoms 3

Testing enhances partner notification, improves compliance, and allows targeted therapy. 4

First-Line Treatment Options

Recommended Regimens for Nongonococcal Urethritis:

Option 1: Azithromycin 1 g orally as a single dose 4, 1

• Advantage: Single-dose therapy ensures compliance and allows directly observed treatment 1
• More effective than doxycycline for M. genitalium (85% cure vs 31% cure) 5

Option 2: Doxycycline 100 mg orally twice daily for 7 days 4, 6

• Traditional first-line option
• Less effective for M. genitalium but adequate for C. trachomatis 5

The choice between these depends on local M. genitalium prevalence and resistance patterns. Given this patient's recurrent symptoms, azithromycin may be preferred as M. genitalium causes 10-30% of NGU cases and is associated with treatment failure after doxycycline. 3, 5

Alternative Regimens (if first-line options contraindicated): 4

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

Partner Management (Critical Component)

All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen. 1, 2 This is essential because:

• Reinfection from untreated partners is a leading cause of recurrent urethritis 2
• Partners may be asymptomatic carriers 4

Sexual abstinence is required for 7 days after treatment initiation and until symptoms resolve and partners are adequately treated. 1, 2

Management of Persistent/Recurrent Symptoms

If symptoms persist or recur after initial treatment: 2

Step 1: Confirm objective signs of urethritis still present

• Re-examination for discharge
• Repeat urinalysis or Gram stain
• Do not retreat based on symptoms alone 2

Step 2: Rule out non-compliance or partner reinfection

• If either is present, repeat the initial regimen 4, 2

Step 3: If compliance confirmed and reinfection excluded:

Test for Trichomonas vaginalis using NAAT or culture on intraurethral swab or first-void urine 2

Recommended treatment for persistent urethritis: 2

• Metronidazole 2 g orally as a single dose (for T. vaginalis and anaerobes)
• PLUS Azithromycin 1 g orally as a single dose (if not used initially)

Alternative: Metronidazole 2 g PLUS Erythromycin base 500 mg four times daily for 7 days 4, 2

Step 4: Consider tetracycline-resistant Ureaplasma urealyticum

Some cases of recurrent urethritis after doxycycline are caused by resistant U. urealyticum. 4, 2 The metronidazole-based regimen addresses this.

Follow-Up Strategy

• Return for evaluation only if symptoms persist or recur after completing therapy 1
• Routine post-treatment testing is NOT recommended in asymptomatic patients 1
• If symptoms persist beyond 2 weeks, perform urine culture and antimicrobial susceptibility testing 1
• Rescreen for STIs in 3 months (high reinfection rates) 7

Common Clinical Pitfalls

1. Treating without objective documentation - leads to antibiotic overuse and missed alternative diagnoses 1, 2
2. Failing to treat partners - results in reinfection cycle 2
3. Not considering M. genitalium - causes treatment failure with doxycycline in up to 45% of cases 5
4. Retreating based on symptoms alone - symptoms may persist from non-infectious causes 2

Special Considerations for This Patient

Given this patient's history of two prior UTIs and current recurrent symptoms:

• Strongly consider azithromycin over doxycycline as first-line therapy given possible M. genitalium involvement 5
• Ensure thorough partner evaluation and treatment to break reinfection cycle 2
• If symptoms persist after appropriate treatment, consider referral to urology to evaluate for chronic prostatitis/chronic pelvic pain syndrome 2