What is the next step in managing urethritis that persists after initial STI (Sexually Transmitted Infection) treatment with antibiotics such as azithromycin (Zithromax)?

Management of Persistent Urethritis After Initial STI Treatment

For persistent urethritis after initial treatment with azithromycin, the next step should be treatment with metronidazole 2g orally in a single dose PLUS azithromycin 1g orally in a single dose (if not used for initial episode). 1

Evaluation Before Re-treatment

Before initiating additional treatment, it's crucial to:

• Confirm objective signs of urethritis (not just symptoms)
• Rule out non-compliance with initial treatment
• Rule out reexposure to untreated sexual partners

Objective signs of urethritis include:

• Mucopurulent or purulent urethral discharge
• Gram stain showing ≥5 WBC per oil immersion field
• Positive leukocyte esterase test on first-void urine
• Microscopic examination of first-void urine showing ≥10 WBC per high-power field 1

Treatment Algorithm for Persistent Urethritis

1. First, confirm persistent urethritis:

   • Symptoms alone without objective signs are insufficient for re-treatment 2, 1
   • Perform urethral swab or first-void urine tests to document inflammation

2. If patient was non-compliant or reexposed:

   • Re-treat with the initial regimen 2

3. If compliant and reexposure excluded:

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

4. Consider testing for specific pathogens:

   • T. vaginalis culture using intraurethral swab or first-void urine 2
   • Consider testing for tetracycline-resistant U. urealyticum 2, 1
   • Consider M. genitalium testing if available 1

Rationale for Treatment

Persistent urethritis may be caused by:

• Trichomonas vaginalis infection (treated with metronidazole/tinidazole)
• Tetracycline-resistant Ureaplasma urealyticum (may respond to azithromycin)
• Mycoplasma genitalium (responds better to azithromycin) 1
• Approximately 50% of men with chronic nonbacterial prostatitis/chronic pelvic pain syndrome have evidence of urethral inflammation without identifiable pathogens 2

Patient Management

• Instruct patients to abstain from sexual intercourse until 7 days after therapy is initiated and symptoms have resolved 2, 1
• All sexual partners within the preceding 60 days should be referred for evaluation and treatment 2, 1
• Test for other STIs, including syphilis and HIV 2, 1

Important Caveats

• Persistent symptoms beyond 3 months should prompt evaluation for chronic prostatitis/chronic pelvic pain syndrome 2, 1
• Urologic examinations usually do not reveal a specific etiology for persistent urethritis 2
• Azithromycin should not be relied upon to treat syphilis, which may be masked or delayed by antimicrobial agents used for urethritis 3
• Moxifloxacin 400mg orally once daily for 7 days may be considered for M. genitalium infections not responding to standard therapy 2

Special Considerations

• HIV-infected patients should receive the same treatment regimen as HIV-negative patients 2, 1
• Men with a low probability of T. vaginalis (e.g., MSM) are unlikely to benefit from the addition of metronidazole or tinidazole 2

By following this approach, you can effectively manage persistent urethritis while minimizing unnecessary antibiotic use and preventing complications such as chronic prostatitis or pelvic pain syndrome.