What is the recommended treatment for a typical adult patient with urethral discharge, potentially caused by gonorrhea or chlamydia?

Treatment for Urethral Discharge

For adults with urethral discharge, initiate treatment with azithromycin 1 g orally as a single dose OR doxycycline 100 mg orally twice daily for 7 days after confirming urethritis through objective documentation. 1, 2, 3

Diagnostic Confirmation Required Before Treatment

Before initiating therapy, urethritis must be objectively documented using at least one of the following criteria:

• Mucopurulent or purulent discharge on examination 4
• Gram stain of urethral secretions showing ≥5 white blood cells per oil immersion field (≥2 WBCs per oil immersion field in women) 4, 1
• First-void urine microscopy demonstrating ≥10 white blood cells per high-power field 4
• Positive leukocyte esterase test on first-void urine 4

Critical caveat: Symptoms alone without objective evidence of urethral inflammation are insufficient for diagnosis or treatment initiation. 1 The absence of pyuria does not exclude sexually transmitted urethritis, as urethral swabs and first-catch urine have low sensitivity (29-62%) for detecting polymorphonuclear leukocytes in chlamydial and mycoplasma infections. 5

First-Line Treatment Regimens

Recommended options (choose one):

• Azithromycin 1 g orally as a single dose 4, 1, 3

  • Advantage: Directly observed therapy with improved compliance 4, 1
  • May be more effective for Mycoplasma genitalium infections 4

• Doxycycline 100 mg orally twice daily for 7 days 4, 1, 2

  • First-line for patients positive for both Mycoplasma genitalium and Ureaplasma 6

Both regimens are highly effective for chlamydial urethritis and have equivalent efficacy. 4, 1

Alternative Regimens

If first-line agents cannot be used:

• Erythromycin base 500 mg orally four times daily for 7 days 4, 6
• Erythromycin ethylsuccinate 800 mg orally four times daily for 7 days 4, 6
• Levofloxacin 500 mg orally once daily for 7 days 4, 6
• Ofloxacin 300 mg orally twice daily for 7 days 4, 6

When to Treat Empirically for Gonorrhea

If gonococcal infection is suspected or confirmed, add ceftriaxone:

• Ceftriaxone 500 mg IM as a single dose (for patients <150 kg) PLUS azithromycin 1 g orally 5, 7
• This dual therapy addresses both gonorrhea and likely chlamydial co-infection 8, 7

Empiric treatment for both gonorrhea and chlamydia is indicated for:

• Patients at high risk who are unlikely to return for follow-up (e.g., adolescents with multiple partners) 4
• Patients with severe urethritis or inability to follow up 5

Testing Strategy

All patients with confirmed or suspected urethritis should be tested for both N. gonorrhoeae and C. trachomatis before or at time of treatment. 4, 1

• Perform nucleic acid amplification testing (NAAT) on first-void urine or urethral swab 5
• Gram stain is the preferred rapid diagnostic test for documenting urethritis and identifying gonococcal infection (intracellular Gram-negative diplococci) 4, 5
• If NAAT is positive for gonorrhea, obtain culture for antimicrobial susceptibility testing 5

For mild symptoms with reliable follow-up: Consider delaying treatment until NAAT results guide pathogen-directed therapy. 5

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same regimen as the index patient. 4, 1, 6

• Partners should be treated even if asymptomatic 1, 6
• Sexual abstinence is required for 7 days after treatment initiation and until symptoms resolve and partners are adequately treated 4, 1, 6

Follow-Up and Persistent Symptoms

Patients should return for evaluation only if symptoms persist or recur after completing therapy. 4, 1

• Routine post-treatment testing is not recommended in asymptomatic patients 1
• Symptoms alone without objective signs of urethritis are not sufficient for re-treatment 4

For persistent or recurrent urethritis:

1. Re-treat with the initial regimen if non-compliant or re-exposed to untreated partner 4, 6
2. If compliance was adequate and partner was treated, perform testing for Trichomonas vaginalis using NAAT or culture 1
3. Consider treatment with metronidazole 2 g orally as a single dose PLUS azithromycin 1 g orally (if azithromycin was not used initially) 1
4. For persistent cases, consider Mycoplasma genitalium with possible macrolide resistance, which may require moxifloxacin 400 mg daily for 7-14 days 5

Special Populations

Pregnant patients:

• Azithromycin 1 g orally as a single dose is the preferred treatment due to safety and effectiveness 1
• Doxycycline and fluoroquinolones are contraindicated in pregnancy 1

HIV-infected patients:

• Treat with the same regimens as HIV-negative patients 6

Critical Pitfalls to Avoid

• Do not defer treatment if objective signs of urethritis are present and patient is unlikely to return for follow-up 4
• Do not re-treat based on symptoms alone without documenting objective signs of urethritis 4
• Always test for syphilis in patients with sexually transmitted urethritis, as high-dose short-course antibiotics may mask incubating syphilis 3
• Ensure medication is provided directly in clinic when possible to improve compliance, especially for multi-dose regimens 4