What is the first-line treatment for urethritis?

First-Line Treatment for Urethritis

The first-line treatment for urethritis is azithromycin 1g orally in a single dose or doxycycline 100mg orally twice daily for 7 days. 1

Diagnostic Approach

Before initiating treatment, confirm the diagnosis of urethritis with at least one of the following:

• Mucopurulent urethral discharge
• Gram stain of urethral secretions showing ≥2 WBCs per oil immersion field
• First-void urine with ≥10 WBCs per high-power field
• Positive leukocyte esterase test on first-void urine 1

Treatment Algorithm

First-Line Treatment Options:

1. Azithromycin: 1g orally in a single dose

   • Advantages: Single-dose therapy improves compliance
   • Particularly effective against Chlamydia trachomatis

2. Doxycycline: 100mg orally twice daily for 7 days

   • Equally effective as azithromycin for clinical cure 2
   • Preferred for non-gonococcal urethritis

Pathogen-Specific Considerations:

When gonorrhea is suspected or confirmed:

• Add ceftriaxone 1g IM or IV as a single dose 1
• This combination addresses both gonococcal and non-gonococcal causes

For confirmed pathogens:

• Chlamydia trachomatis: Either azithromycin or doxycycline as above 3, 4
• Mycoplasma genitalium: Azithromycin 500mg on day 1, then 250mg daily for 4 days 1
• Ureaplasma urealyticum: Doxycycline 100mg twice daily for 7 days 1
• Trichomonas vaginalis: Metronidazole 2g orally in a single dose 1

Alternative Regimens

If first-line treatments are contraindicated:

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

Management of Persistent or Recurrent Urethritis

If symptoms persist after initial treatment:

1. Confirm objective signs of urethritis before retreatment
2. Rule out reinfection or non-compliance
3. Consider testing for T. vaginalis and tetracycline-resistant U. urealyticum
4. Recommended regimen for persistent urethritis:
   • Metronidazole 2g orally in a single dose PLUS
   • Azithromycin 1g orally in a single dose (if not used initially) 1

Partner Management

• All sexual partners within the preceding 60 days should be referred for evaluation and treatment
• Partners should receive the same treatment as the index patient
• Patients and partners should abstain from sexual intercourse until:
  • 7 days after treatment is initiated
  • Symptoms have resolved
  • Partners have been adequately treated 5

Follow-Up Recommendations

• No test of cure is needed if symptoms resolve
• Patients should return for evaluation if symptoms persist or recur
• Repeat screening is recommended 3 months after treatment 5
• For M. genitalium infections, test of cure should be collected no earlier than 3 weeks after treatment 6

Special Considerations

• HIV-infected patients should receive the same treatment regimens as HIV-negative patients 1
• Antimicrobial resistance is an increasing concern, particularly with M. genitalium
• Single-dose azithromycin may select for macrolide-resistant M. genitalium strains; consider this when choosing initial therapy 6

The evidence strongly supports either azithromycin or doxycycline as first-line therapy for urethritis, with comparable clinical cure rates of approximately 80% 2. Treatment choice should be guided by local resistance patterns and patient-specific factors such as compliance concerns.