What is the best course of treatment for a young to middle-aged adult male patient with a swollen penile meatus, negative STI (Sexually Transmitted Infection) test result, and no known history of trauma or previous urological conditions?

Swollen Penile Meatus with Negative STI Testing

Primary Recommendation

For a young to middle-aged adult male with isolated swelling of the penile meatus and confirmed negative STI testing, the most likely diagnosis is penile friction edema (also called non-venereal penile edema), which requires only temporary sexual abstinence for several weeks until resolution—no antibiotics are indicated. 1

Diagnostic Approach

Initial Differential Diagnosis

The swollen penile meatus with negative STI testing narrows the differential to non-infectious causes:

• Penile friction edema: Results from traumatic lymphatic drainage disruption during sexual activity, presenting as localized or diffuse penile swelling without infectious etiology 1
• Bacterial cellulitis: Presents with erythema, warmth, tenderness, and systemic signs—requires ultrasound showing increased soft tissue echogenicity and Doppler signal if suspected 2
• Urethral stricture: Typically presents with obstructive urinary symptoms rather than isolated meatal swelling 3

Key Clinical Features to Assess

Examine for infectious signs that would change management:

• Erythema, warmth, and tenderness suggest bacterial cellulitis requiring antibiotics 2
• Fever or systemic symptoms warrant hospitalization and IV antibiotics 4
• Urethral discharge (even minimal) requires urethral swab Gram stain showing ≥5 polymorphonuclear leukocytes per oil immersion field to diagnose urethritis 4
• Recent sexual trauma or vigorous activity supports friction edema diagnosis 1

Rule out urethritis despite negative STI testing:

• Perform urethral Gram stain—if negative, examine first-void urine for leukocytes with culture 4
• Consider non-gonococcal, non-chlamydial urethritis causes (Ureaplasma urealyticum 20-40%, Trichomonas vaginalis 2-5%) 4

Treatment Algorithm

If No Signs of Infection (Most Likely Scenario)

Diagnosis: Penile Friction Edema

• Prescribe complete sexual abstinence for several weeks until swelling fully resolves 1
• Reassure patient this is a benign traumatic disorder of lymphatic drainage, not a venereal disease 1
• No antibiotics indicated 1
• Follow-up in 2-3 weeks to confirm resolution

If Signs of Cellulitis Present

Diagnosis: Bacterial Cellulitis

• Point-of-care ultrasound can confirm diagnosis showing increased soft tissue echogenicity with markedly increased Doppler signal 2
• Initiate broad-spectrum antibiotics covering Streptococcus species (most common pathogen in penile cellulitis) 2, 5
• Consider Streptococcus intermedius in cases following sexual trauma, which can rapidly progress to abscess formation within 24 hours 5
• Hospitalize if severe pain, fever, or rapid progression 4

If Urethritis Confirmed (Despite Negative Initial STI Testing)

For men <35 years:

• Ceftriaxone 250 mg IM single dose PLUS Doxycycline 100 mg orally twice daily for 10 days to cover potential false-negative STI testing and non-gonococcal urethritis 4, 6

For men ≥35 years:

• Ofloxacin 300 mg orally twice daily for 10 days to cover enteric organisms 4, 7

Critical Pitfalls to Avoid

Do Not Empirically Treat with Antibiotics

The provided guidelines specifically address urethritis and epididymitis—not isolated meatal swelling with negative STI testing 4. Overtreatment with antibiotics when friction edema is the diagnosis wastes resources and promotes resistance 1.

Reassess if No Improvement

• If swelling persists beyond 3-4 weeks of sexual abstinence, consider alternative diagnoses including urethral stricture, lymphatic obstruction, or rare causes 1, 3
• Persistent symptoms warrant urology referral for further evaluation 4

Watch for Rapid Progression

• Cellulitis can progress to abscess formation within 24 hours, particularly with Streptococcus intermedius 5
• Instruct patient to return immediately if erythema, warmth, fever, or worsening pain develops 2, 5

Consider Lichen Sclerosus in Recurrent Cases

• Recurrent meatal swelling or stenosis may indicate lichen sclerosus requiring meatoplasty rather than conservative management 3

Follow-Up Strategy

• Schedule 2-3 week follow-up to confirm resolution with sexual abstinence 1
• If improved but not resolved, extend abstinence period 1
• If no improvement or worsening, perform comprehensive urologic evaluation including possible ultrasound and urology referral 2, 3