What is the initial treatment for a sexually active adult male patient presenting with urethritis?

Treatment of Male Urethritis

Initial Empiric Treatment

For sexually active adult males presenting with urethritis, initiate immediate dual therapy with azithromycin 1g orally as a single dose OR doxycycline 100mg orally twice daily for 7 days, combined with treatment for gonorrhea if gonococcal infection cannot be ruled out. 1, 2

Recommended First-Line Regimens

The CDC recommends two equally effective options for non-gonococcal urethritis (NGU):

• Azithromycin 1g orally in a single dose - Preferred when compliance is a concern and particularly effective against Mycoplasma genitalium 1, 2, 3
• Doxycycline 100mg orally twice daily for 7 days - Highly effective for chlamydial urethritis and remains the most reliable agent against Ureaplasma species 1, 2, 3

Critical decision point: If clinic-based diagnostic tools (Gram stain microscopy) are unavailable or if gonococcal infection cannot be excluded, treat empirically for both gonorrhea and chlamydia with dual therapy. 1, 2

When to Treat Empirically

Initiate treatment immediately if the patient has any one of the following diagnostic criteria:

• Mucopurulent or purulent urethral discharge on examination 1, 2
• Positive leukocyte esterase test on first-void urine 1, 2
• ≥10 white blood cells per high-power field on microscopic examination of first-void urine sediment 1, 2

Important caveat: If none of these criteria are present, empiric treatment is recommended only for high-risk patients unlikely to return for follow-up evaluation. 1, 2

Alternative Regimens

For patients who cannot tolerate first-line therapy:

• Erythromycin base 500mg orally four times daily for 7 days 1
• Erythromycin ethylsuccinate 800mg orally four times daily for 7 days 1
• Levofloxacin 500mg orally once daily for 7 days 1
• Ofloxacin 300mg orally twice daily for 7 days 1

Testing Requirements

All patients with suspected urethritis must be tested for both Neisseria gonorrhoeae and Chlamydia trachomatis using nucleic acid amplification tests (NAATs), which are more sensitive than culture. 1, 2

Testing is critical because:

• Both infections are reportable conditions 1
• Specific diagnosis enhances partner notification and treatment compliance 1, 2
• C. trachomatis accounts for 15-55% of NGU cases 1
• Coinfection rates are high (80% of men with chlamydia also had gonorrhea in one study) 4

Partner Management Protocol

All sexual partners within the preceding 60 days must be referred for evaluation and treatment, regardless of whether a specific pathogen is identified. 1, 2

Sexual Abstinence Requirements

Both patient and partners must abstain from sexual intercourse:

• For 7 days after initiating single-dose therapy (azithromycin) 1, 2
• Until completion of 7-day regimen (doxycycline) 1, 2
• Until all symptoms have completely resolved 1, 2
• Until all sex partners have been adequately treated 1, 2

Common pitfall: Treatment failure commonly occurs when patients resume intercourse before both partners complete therapy. 5

Medication Administration

To maximize compliance, medications should be dispensed on-site in the clinic, and the first dose should be directly observed whenever possible. 1

For doxycycline specifically:

• Administer with adequate fluid to reduce risk of esophageal irritation and ulceration 3
• May be given with food or milk if gastric irritation occurs (absorption not significantly affected) 3

Follow-Up Recommendations

Patients should return for evaluation only if symptoms persist or recur after completing therapy. 1, 2

Test-of-Cure Guidelines

• Not recommended for asymptomatic patients who received recommended treatment and completed therapy 1, 2
• Repeat testing at 3-6 months is recommended due to high reinfection rates (not to assess cure, but to detect reinfection) 1, 2

Important distinction: Symptoms alone, without documentation of signs or laboratory evidence of urethral inflammation, are not sufficient basis for retreatment. 1

Management of Persistent or Recurrent Urethritis

Before initiating further antimicrobial therapy, confirm objective signs of urethritis are present. 1, 2

If urethritis is confirmed and patient was compliant with initial treatment and reexposure is excluded:

Recommended regimen for persistent/recurrent cases:

• Metronidazole 2g orally in a single dose OR Tinidazole 2g orally in a single dose 1, 2
• PLUS Azithromycin 1g orally in a single dose (if not used for initial episode) 1, 2

This regimen targets Trichomonas vaginalis and tetracycline-resistant Ureaplasma urealyticum, which are common causes of persistent NGU. 1

Clinical pearl: Approximately 50% of men with chronic symptoms have evidence of urethral inflammation without identifiable microbial pathogens, suggesting chronic prostatitis/chronic pelvic pain syndrome. 1

Additional Testing Requirements

All patients diagnosed with urethritis should receive testing for other STDs, including syphilis and HIV. 1, 2

This is critical because:

• HIV prevalence among men with urethritis can be as high as 28.5% 4
• Urethritis is associated with increased HIV concentration in semen 6
• Antimicrobial agents used for urethritis may mask or delay symptoms of incubating syphilis 7

Special Populations

HIV-infected patients should receive the same treatment regimens as HIV-negative individuals. 1, 8

Common Pitfalls to Avoid

• Never delay partner treatment - waiting for partner symptoms increases reinfection risk for the index patient 5
• Never treat without ensuring sexual abstinence - this is the most common cause of treatment failure 5
• Never assume asymptomatic partners are uninfected - they can transmit infection and must be treated 5
• Never extend antimicrobial duration without objective signs - the value of extending therapy for persistent symptoms without objective urethritis has not been demonstrated 1