What is the appropriate diagnosis and treatment for a sexually active male patient presenting with penile discharge, considering potential underlying causes such as gonorrhea, chlamydia, syphilis, and HIV?

Diagnosis and Treatment of Male Penile Discharge

A sexually active male presenting with penile discharge should be treated empirically with ceftriaxone 250 mg IM plus doxycycline 100 mg orally twice daily for 7 days to cover both gonorrhea and chlamydia, as these are the two primary bacterial pathogens responsible for urethritis. 1, 2

Diagnostic Confirmation

Before or concurrent with treatment, confirm urethritis is present by documenting at least one of the following:

• Mucopurulent or purulent discharge 1
• Gram stain showing ≥5 polymorphonuclear leukocytes per oil immersion field in urethral secretions 1
• Positive leukocyte esterase test on first-void urine 1, 3
• ≥10 white blood cells per high-power field in urine sediment 3

Obtain nucleic acid amplification tests (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, 4 Testing is critical because both infections are reportable and a specific diagnosis improves compliance and partner notification. 1

First-Line Empiric Treatment

When diagnostic tools are unavailable or while awaiting test results, treat for both gonorrhea and chlamydia:

Recommended Regimen:

• Ceftriaxone 250 mg IM single dose PLUS
• Doxycycline 100 mg orally twice daily for 7 days 1, 2, 3

This combination addresses the two most important bacterial pathogens and prevents complications including epididymitis, Reiter's syndrome, and transmission to partners. 1

Alternative Regimens

If doxycycline is contraindicated or not tolerated:

• Azithromycin 1 g orally as a single dose can replace doxycycline for chlamydia coverage 5
• Erythromycin base 500 mg orally 4 times daily for 7 days 1
• Erythromycin ethylsuccinate 800 mg orally 4 times daily for 7 days 1

For patients unable to tolerate high-dose erythromycin, use lower doses extended to 14 days. 1

Additional Testing Requirements

All patients with urethral discharge must receive:

• Syphilis serology (sequential treponemal and nontreponemal antibody testing) 6, 4
• HIV counseling and testing 6

This is critical because antimicrobial agents used for urethritis may mask or delay symptoms of incubating syphilis. 5 If syphilis is confirmed, treat with penicillin or doxycycline 100 mg orally twice daily for 2 weeks (early syphilis) or 4 weeks (late syphilis). 2

Partner Management

Sexual partners from the 60 days preceding symptom onset must be referred for evaluation and treatment. 7, 6 Expedited partner treatment (giving prescriptions to partners who haven't been examined) is advocated by the CDC and approved in many states. 3

Patients should abstain from sexual intercourse until both they and their partners complete treatment and are symptom-free. 6

Follow-Up Protocol

Patients must return for reevaluation if symptoms persist or recur after completing therapy. 1, 7

For persistent or recurrent urethritis:

• If non-compliant or re-exposed to untreated partner: Re-treat with initial regimen 1
• If compliant with no re-exposure: Perform wet mount and culture for T. vaginalis, then retreat with erythromycin base 500 mg orally 4 times daily for 14 days to cover tetracycline-resistant U. urealyticum 1
• Consider alternative diagnoses including M. genitalium (treat with moxifloxacin), trichomoniasis (treat with metronidazole 2 g single dose), or HSV 7, 4

Critical Pitfalls to Avoid

Never rely on patient-reported symptoms alone without microscopic confirmation, as approximately 53%-100% of extragenital gonorrhea and chlamydia infections are asymptomatic or minimally symptomatic. 4

Do not use azithromycin monotherapy for gonorrhea due to widespread antimicrobial resistance. 4 Always combine with ceftriaxone.

Always evaluate and treat sexual partners to prevent reinfection, as untreated partners are the most common cause of treatment failure. 7

Rule out complications such as epididymitis (unilateral testicular pain and swelling) which requires extended treatment for at least 10 days. 6, 2