What is the treatment for urethritis?

Treatment of Urethritis

For confirmed urethritis, initiate empiric dual therapy immediately with Ceftriaxone 250-500 mg IM single dose PLUS either Azithromycin 1 g orally single dose OR Doxycycline 100 mg orally twice daily for 7 days to cover both gonorrhea and chlamydia. 1

Confirming the Diagnosis Before Treatment

Before initiating therapy, urethritis should be documented by at least one of the following criteria: 2, 1

• Mucopurulent or purulent urethral discharge (visible on examination) 2
• Gram stain of urethral secretions showing ≥5 WBCs per oil immersion field (preferred rapid diagnostic test) 2
• Positive leukocyte esterase test on first-void urine 2
• Microscopic examination of first-void urine showing ≥10 WBCs per high-power field 2

If none of these criteria are present, defer treatment and test for N. gonorrhoeae and C. trachomatis using nucleic acid amplification tests (NAATs), then follow closely. 2, 3

First-Line Empiric Treatment Regimens

Dual Coverage is Mandatory

The CDC explicitly recommends dual therapy covering both gonorrhea and chlamydia because: 1

• Co-infection with both pathogens is extremely common 1, 4
• Most sexually transmitted urethritis in men under 35 is caused by C. trachomatis or N. gonorrhoeae 1
• Delaying treatment increases risk of complications (epididymitis) and ongoing transmission 1

Recommended Regimen

For gonorrhea coverage: 1

• Ceftriaxone 250-500 mg IM as a single dose 1

PLUS for chlamydia/NGU coverage (choose one): 2, 1

• Azithromycin 1 g orally as a single dose (preferred for compliance and directly observed therapy) 2, 1
• OR Doxycycline 100 mg orally twice daily for 7 days 2, 1

Azithromycin has the advantage of single-dose administration ensuring compliance and is particularly effective against Mycoplasma genitalium, which may respond better to azithromycin than doxycycline. 2, 1

Alternative Regimens (if first-line not tolerated)

For chlamydia/NGU coverage: 2

• Erythromycin base 500 mg orally four times daily for 7 days 2
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 2
• Ofloxacin 300 mg orally twice daily for 7 days 2
• Levofloxacin 500 mg orally once daily for 7 days 2

When to Treat Empirically Without Confirmed Urethritis

Empiric treatment without documentation of urethritis is recommended ONLY for patients at high risk for infection who are unlikely to return for follow-up evaluation (e.g., adolescents with multiple partners). 2, 3 These patients should receive full dual coverage for both gonorrhea and chlamydia. 2, 3

Critical Management Steps

Testing Requirements

• All patients with confirmed or suspected urethritis must be tested for both N. gonorrhoeae and C. trachomatis using NAATs 2, 1
• Perform HIV and syphilis testing as part of comprehensive STI screening 1
• Testing for M. genitalium should be considered if available 5

Sexual Activity Restrictions

Both patient and all sexual partners must abstain from sexual intercourse until 7 days after therapy initiation AND symptom resolution. 2, 1, 6

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen, regardless of whether a specific pathogen is identified in the index patient. 2, 1, 6 Partners should receive treatment effective against chlamydia even if testing is negative. 1, 6

Management of Persistent or Recurrent Urethritis

Objective signs of urethritis must be re-documented before initiating additional antimicrobial therapy. 2, 6 Symptoms alone without laboratory evidence are not sufficient basis for re-treatment. 2

Step-by-Step Approach

1. Re-confirm urethritis with microscopy (≥5 WBCs per oil immersion field on Gram stain or ≥10 WBCs per high-power field in urine) 2, 6

2. Assess for non-compliance or partner reinfection - if either is present, re-treat with the initial regimen 2, 6

3. If compliant and reinfection excluded, test for Trichomonas vaginalis (culture of intraurethral swab and first-void urine) 2, 6

4. Consider tetracycline-resistant Ureaplasma urealyticum 2, 6

Recommended Treatment for Persistent/Recurrent Urethritis

If the patient was compliant with initial therapy and reinfection is excluded: 2, 6

• Metronidazole 2 g orally as a single dose (or Tinidazole 2 g orally single dose) 2, 6
• PLUS Erythromycin base 500 mg orally four times daily for 7 days 2
• OR Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 2
• OR if azithromycin was not used initially, Azithromycin 1 g orally single dose 6

Alternative: Moxifloxacin 400 mg orally once daily for 7-14 days (particularly for macrolide-resistant M. genitalium) 6, 5

Follow-Up Recommendations

• Patients should return for evaluation if symptoms persist or recur after completion of therapy 2, 6
• Test-of-cure is not recommended for asymptomatic patients who received recommended treatment 6
• Consider repeat testing 3-6 months after treatment due to high reinfection rates 3, 6
• If positive for M. genitalium, test-of-cure samples should be collected no earlier than 3 weeks after start of treatment 5
• Failure to improve within 3 days requires diagnostic reevaluation 1

Common Pitfalls to Avoid

• Do NOT treat for gonorrhea alone without chlamydia coverage - co-infection is extremely common 1
• Do NOT treat based on symptoms alone without objective evidence of urethritis unless the patient meets high-risk criteria for empiric treatment 3
• Do NOT forget to test for HIV and syphilis - all patients with sexually transmitted urethritis should have serologic testing for syphilis performed at diagnosis 2, 1
• Do NOT use azithromycin as first-line treatment without test-of-cure for M. genitalium - this will select and increase macrolide-resistant strains in the population 5
• Do NOT rely on semen analysis or leukocytospermia to diagnose urethritis - proper urethral testing is required 6

Special Considerations

HIV-Positive Patients

Patients with urethritis who are HIV-positive should receive the same treatment regimen as HIV-negative patients. 2, 1 Gonococcal and chlamydial urethritis may facilitate HIV transmission. 2, 4

Medication Provision

To improve compliance, medication should ideally be provided directly in the clinic or healthcare provider's office at the time of diagnosis. 2, 1