What is the treatment for urethritis?

Treatment of Urethritis

First-Line Empiric Treatment

For confirmed urethritis, initiate dual therapy immediately with Ceftriaxone 250-500 mg IM as a single dose PLUS either Azithromycin 1 g orally as a single dose OR Doxycycline 100 mg orally twice daily for 7 days. 1

This dual-coverage approach is essential because:

• Most sexually transmitted urethritis in men under 35 is caused by C. trachomatis or N. gonorrhoeae, and co-infection with both pathogens is common 1
• Treatment should cover both organisms empirically before culture results are available to achieve microbiologic cure, prevent transmission, and decrease complications such as epididymitis 1
• The CDC explicitly recommends this dual approach as first-line therapy 1

Confirming the Diagnosis

Before initiating treatment, document urethritis using at least one of the following criteria 2, 1:

• Mucopurulent or purulent urethral discharge (most specific finding) 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 2, 3.

Exception for High-Risk Patients

Empiric treatment without documented urethritis is recommended only for patients at high risk who are unlikely to return for follow-up (e.g., adolescents with multiple partners), and these patients should receive dual coverage for both gonorrhea and chlamydia 2, 3.

Alternative Regimens for Nongonococcal Urethritis

If gonococcal infection has been ruled out, the following are acceptable alternatives 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

Note: Azithromycin may be superior to doxycycline for infections with M. genitalium, which can cause nongonococcal urethritis 2. The single-dose regimen also ensures compliance and allows directly observed therapy 2, 1.

Management of Persistent or Recurrent Urethritis

If symptoms persist after initial treatment 2:

1. Re-confirm objective signs of urethritis before retreating—symptoms alone without documentation are insufficient 2
2. Assess compliance and partner treatment—if non-compliant or reexposed to untreated partner, retreat with initial regimen 2
3. If compliant and no reexposure, obtain culture for T. vaginalis and consider tetracycline-resistant U. urealyticum 2, 4

Recommended regimen for persistent/recurrent urethritis 2, 4:

• Metronidazole 2 g orally as a single dose (or Tinidazole 2 g orally as a single dose) 4
• PLUS Azithromycin 1 g orally as a single dose (if not used initially) 4
• OR Erythromycin base 500 mg orally four times daily for 7 days 2

Critical Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated 2, 1:

• Partners should receive treatment effective against chlamydia regardless of whether a specific pathogen is identified in the index patient 1, 3
• Both patient and partners must abstain from sexual intercourse until 7 days after therapy initiation and symptom resolution 2, 1, 4
• Expedited partner treatment (giving patients prescriptions for partners who have not been examined) is advocated by the CDC and approved in many states 5

Testing and Follow-Up

All patients with confirmed or suspected urethritis should be tested for both gonorrhea and chlamydia using nucleic acid amplification tests 2, 1:

• Testing for chlamydia is strongly recommended because specific diagnosis enhances partner notification and improves compliance 2
• All patients with sexually transmitted urethritis should have serologic testing for syphilis and HIV at the time of diagnosis 1, 6, 5

Follow-up is indicated only if symptoms persist or recur after treatment 2, 4:

• Test-of-cure is not recommended for asymptomatic patients who received recommended treatment 4
• Consider repeat testing 3-6 months after treatment due to high reinfection rates 3, 4
• Failure to improve within 3 days requires diagnostic reevaluation 1

Common Pitfalls to Avoid

• Do not treat for gonorrhea alone without chlamydia coverage, as co-infection is common 1
• Do not treat based on symptoms alone without objective evidence of urethritis unless the patient meets high-risk criteria for empiric treatment 2, 3
• Do not forget HIV and syphilis testing as part of the comprehensive STI panel 1, 6
• Do not rely on azithromycin alone to treat syphilis—antimicrobial agents used in high doses for short periods may mask or delay symptoms of incubating syphilis 6
• Persistence of symptoms beyond 3 months should alert clinicians to the possibility of chronic prostatitis/chronic pelvic pain syndrome 2

Special Considerations

HIV-positive patients with urethritis should receive the same treatment regimen as HIV-negative patients 2, 1. Gonococcal and nongonococcal urethritis may facilitate HIV transmission and increase HIV concentration in semen 2, 5.