What is the treatment for urethritis?

Treatment of Urethritis

For acute urethritis, initiate empiric treatment with azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days, targeting the most common pathogens Chlamydia trachomatis and Ureaplasma urealyticum. 1

Diagnostic Confirmation Before Treatment

Before initiating therapy, confirm urethritis is present using objective criteria 1:

• Mucopurulent or purulent urethral discharge on examination 1
• Gram stain showing ≥5 white blood cells per oil immersion field (preferred rapid diagnostic test) 1
• First-void urine with positive leukocyte esterase test OR ≥10 white blood cells per high-power field on microscopy 1

Critical pitfall: Do not treat based on symptoms alone without objective evidence of urethral inflammation 1, 2, 3. If none of these criteria are present, defer treatment and test for N. gonorrhoeae and C. trachomatis 1.

Pathogen-Specific Testing

Perform nucleic acid amplification testing (NAAT) on first-void urine or urethral swab before treatment to identify specific pathogens 1:

• Test for both N. gonorrhoeae and C. trachomatis in all patients 1, 3
• Gram stain can provide immediate differentiation between gonococcal and non-gonococcal urethritis 1
• For gonorrhea-positive cases, obtain urethral swab culture before treatment to assess antimicrobial resistance 1

First-Line Treatment Regimens

For Non-Gonococcal Urethritis (NGU)

Recommended regimens 1:

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

Alternative regimens if first-line options cannot be used 1:

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

For Gonococcal Urethritis

Dual therapy is mandatory to cover both gonorrhea and chlamydia 1, 4:

• Ceftriaxone 1 g intramuscularly or intravenously as a single dose 1
• PLUS Azithromycin 1 g orally as a single dose 1

Alternative regimens for gonococcal infection 1:

• Cefixime 400 mg orally single dose PLUS azithromycin 1 g orally single dose
• In cephalosporin allergy: Gentamicin 240 mg intramuscularly single dose PLUS azithromycin 2 g orally single dose
• Gemifloxacin 320 mg orally single dose PLUS azithromycin 2 g orally single dose

Pathogen-Specific Treatment

For confirmed Mycoplasma genitalium 1:

• Azithromycin 500 mg orally on day 1, then 250 mg daily for 4 days
• If macrolide resistance: Moxifloxacin 400 mg orally once daily for 7-14 days

For Trichomonas vaginalis 1:

• Metronidazole 2 g orally as a single dose
• OR Tinidazole 2 g orally as a single dose
• Alternative: Metronidazole 500 mg orally twice daily for 7 days

Special Population: Pregnancy

In pregnant patients, azithromycin 1 g orally as a single dose is the preferred treatment because it is safe and effective 5, 3, 6:

• Doxycycline and fluoroquinolones are contraindicated in pregnancy 3
• Alternative: Erythromycin base 500 mg orally four times daily for 7 days 5, 6
• For urogenital chlamydial infections in pregnancy: Erythromycin 500 mg orally four times daily for at least 7 days 6

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated 1, 2, 3:

• Partners should receive the same treatment regimen as the index patient 2, 3
• Both patient and partners must abstain from sexual intercourse for 7 days after treatment initiation and until symptoms resolve 1, 2, 3
• Expedited partner treatment (giving prescriptions to partners without examination) is advocated by the CDC and approved in many states 4

Management of Persistent or Recurrent Urethritis

If symptoms persist or recur after completing therapy, follow this algorithm 1, 2:

Step 1: Confirm Objective Signs

• Re-document urethritis using the same objective criteria (discharge, WBC count) 1, 2
• Do not re-treat based on symptoms alone 1, 2

Step 2: Assess Compliance and Re-exposure

• If non-compliant with initial regimen OR re-exposed to untreated partner: repeat the initial regimen 1, 2

Step 3: Test for Additional Pathogens

• Perform culture or NAAT for Trichomonas vaginalis using intraurethral swab or first-void urine 1, 2
• Consider testing for tetracycline-resistant Ureaplasma urealyticum 2

Step 4: Treat Persistent Urethritis

Recommended regimen 1, 2:

• 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 for initial episode)

Alternative regimen 1:

• Metronidazole 2 g orally as a single dose PLUS Erythromycin base 500 mg orally four times daily for 7 days

For persistent NGU after doxycycline 1, 2:

• Azithromycin 500 mg orally on day 1, then 250 mg daily for 4 days
• If macrolide-resistant M. genitalium detected: Moxifloxacin 400 mg orally once daily for 7-14 days

Follow-Up Recommendations

• Patients should return only if symptoms persist or recur after completing therapy 1, 3
• Routine post-treatment testing is not recommended in asymptomatic patients 3
• For women whose symptoms do not resolve or recur within 2 weeks: perform urine culture and antimicrobial susceptibility testing 3
• If symptoms persist beyond 3 months, consider chronic prostatitis/chronic pelvic pain syndrome 2

Common Pitfalls to Avoid

• Never treat without objective documentation of urethritis 1, 2, 3
• Do not fail to address partner treatment and potential reinfection 2
• Always test for both gonorrhea and chlamydia before or at treatment initiation 3
• Obtain culture for gonorrhea to assess resistance patterns, as antimicrobial resistance is emerging 1, 7
• Remember that urologic examinations usually do not reveal a specific etiology in persistent cases 1, 2