What is the appropriate diagnosis and treatment for a patient presenting with penile discharge, potentially indicating a sexually transmitted infection (STI) such as gonorrhea, chlamydia, or trichomoniasis?

Diagnosis and Treatment of Penile Discharge

For a patient presenting with penile discharge, empirically treat with ceftriaxone 250 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 to cover both gonorrhea and chlamydia. 1, 2, 3

Diagnostic Approach

Document urethritis before initiating treatment using any of the following criteria: 4, 1

• Visible mucopurulent or purulent discharge 4
• Gram stain of urethral secretions showing ≥5 WBCs per oil immersion field (preferred rapid diagnostic test—highly sensitive and specific for both urethritis and gonococcal infection) 4
• Positive leukocyte esterase test on first-void urine OR ≥10 WBCs per high-power field on microscopic examination 4, 1

Obtain nucleic acid amplification testing (NAAT) for both N. gonorrhoeae and C. trachomatis on first-void urine or urethral swab, as these tests have sensitivities of 86.1%-100% and specificities of 97.1%-100%. 1, 5 The absence of visible discharge does not exclude urethritis, particularly with chlamydial infections. 1

Key Diagnostic Considerations

• Gram stain can immediately identify gonococcal infection by demonstrating WBCs containing intracellular Gram-negative diplococci 4
• C. trachomatis causes 30-40% of non-gonococcal urethritis cases in young males with new sexual contact 1
• Co-infection with gonorrhea and chlamydia is extremely common, making dual coverage essential 2, 6
• Approximately 53-100% of extragenital gonorrhea and chlamydia infections are asymptomatic, emphasizing the need for testing even with minimal symptoms 5

Empiric Treatment Regimen

Initiate treatment as soon as possible after diagnosis without waiting for test results. 4, 1

Recommended First-Line Therapy

Dual therapy is mandatory to cover both gonorrhea and chlamydia: 1, 2, 5

• Ceftriaxone 250 mg IM as a single dose 1, 2
• PLUS either:
  • Azithromycin 1 g orally as a single dose (preferred for compliance—directly observed therapy) 4, 7, OR
  • Doxycycline 100 mg orally twice daily for 7 days 4, 1, 3

Alternative Regimens (if first-line unavailable)

If doxycycline or azithromycin cannot be used: 4

• Erythromycin base 500 mg orally four times daily for 7 days 4
• Ofloxacin 300 mg orally twice daily for 7 days 4

Provide medication in the clinic and administer directly when possible to ensure compliance, particularly with single-dose regimens. 4, 1

Critical Management Steps

Partner Management

All sexual partners within the preceding 60 days must be evaluated and treated with the same empiric dual therapy regimen (ceftriaxone plus azithromycin or doxycycline). 1, 2 If the last sexual contact was >60 days before diagnosis, treat the most recent partner. 2

Both patient and partners must abstain from sexual intercourse for 7 days after treatment initiation and until complete symptom resolution. 1, 2

Additional Testing Requirements

Perform syphilis serology and HIV testing at diagnosis for all patients with sexually transmitted urethritis. 1, 2, 7 STIs increase HIV acquisition and transmission risk by 2- to 5-fold. 8

Follow-Up and Persistent Symptoms

Instruct patients to return if symptoms persist or recur after completing therapy. 4, 1

Management of Treatment Failure

Do not re-treat based on symptoms alone—confirm objective signs of urethritis (discharge or pyuria) before re-treatment. 1

If objective signs persist after appropriate treatment: 4, 1

• Re-treat with the initial regimen if non-compliance or partner re-exposure occurred 4
• If compliance was adequate and partner was treated, consider:
  • Testing for Trichomonas vaginalis (causes 2-5% of NGU cases) 4
  • Extended therapy: Metronidazole 2 g orally as a single dose PLUS azithromycin 1 g orally as a single dose 1
  • Alternative: Erythromycin base 500 mg orally four times daily for 14 days to cover tetracycline-resistant Ureaplasma 4

Repeat screening at 3 months is recommended for all patients treated for STIs to detect reinfection. 1

Common Pitfalls and Caveats

Critical Warnings

• Never treat gonorrhea without also treating chlamydia—co-infection rates are extremely high and reinfection is the primary cause of treatment failure 2, 6
• Single-agent therapy for gonorrhea is inadequate due to antimicrobial resistance patterns 5
• Empiric treatment without documentation of urethritis is only appropriate for high-risk patients unlikely to return (e.g., adolescents with multiple partners) 4
• If treatment is deferred pending test results, ensure close follow-up and treat immediately if positive 4

Special Populations

• HIV-positive patients receive the same treatment regimen as HIV-negative patients, though urethritis may facilitate HIV transmission, making partner treatment particularly important 1
• For sexual assault victims, empirical treatment of chlamydia, gonorrhea, and trichomoniasis is recommended within 72 hours 4

Partner Treatment Considerations

• Patient-delivered partner therapy should not be routinely used in men who have sex with men due to high risk of coexisting undiagnosed STDs or HIV infection—these partners require in-person clinical evaluation 2