How should I treat scrotal cellulitis in an adult male without MRSA risk factors or recent fluoroquinolone use?

Management of Scrotal Cellulitis

For an adult male with scrotal cellulitis without MRSA risk factors or recent fluoroquinolone use, treat with oral cephalexin 500 mg four times daily or dicloxacillin 250-500 mg every 6 hours for 5 days, extending only if clinical improvement has not occurred. 1

Critical Initial Assessment

Before initiating antibiotics, you must immediately evaluate for necrotizing fasciitis (Fournier's gangrene), which can initially present as simple scrotal cellulitis but is a surgical emergency with high mortality. 2 Look specifically for:

• Severe pain out of proportion to examination findings – this is the most sensitive early indicator of necrotizing infection 1
• Rapid progression of erythema or swelling over hours rather than days 1, 2
• "Wooden-hard" subcutaneous tissues suggesting deep fascial involvement 1
• Skin anesthesia, crepitus, bullous changes, or systemic toxicity (fever, hypotension, altered mental status) 1

If any of these warning signs are present, obtain emergent surgical consultation and initiate broad-spectrum IV antibiotics immediately (vancomycin 15-20 mg/kg every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g every 6 hours). 1 Fournier's gangrene masquerading as simple cellulitis is a well-documented diagnostic pitfall with catastrophic consequences if missed. 2

First-Line Antibiotic Selection

For typical nonpurulent scrotal cellulitis without the above red flags:

• Cephalexin 500 mg orally every 6 hours provides excellent coverage against beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus, the primary pathogens in 96% of cellulitis cases 1, 3
• Dicloxacillin 250-500 mg orally every 6 hours is an equally effective alternative beta-lactam 1
• Amoxicillin-clavulanate 875/125 mg twice daily can be considered if broader polymicrobial coverage is desired, though this is typically unnecessary for simple cellulitis 1

Beta-hemolytic streptococci are the predominant pathogens in scrotal cellulitis, often without a discernible portal of entry. 3 Beta-lactam monotherapy achieves 96% clinical success in typical cases. 1

Treatment Duration

• Treat for exactly 5 days if clinical improvement occurs (reduced warmth, tenderness, and erythema) 1
• Extend treatment only if symptoms have not improved within this 5-day timeframe 1
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1

When to Add MRSA Coverage

Do NOT routinely add MRSA coverage for typical scrotal cellulitis. 1 MRSA is an uncommon cause even in high-prevalence settings. 1 Add MRSA-active antibiotics only when specific risk factors are present:

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (SIRS) – fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
• Failure to respond to beta-lactam therapy after 48-72 hours 1

If MRSA coverage is needed, use clindamycin 300-450 mg orally every 6 hours (provides single-agent coverage for both streptococci and MRSA, but only if local clindamycin resistance <10%) 1 or trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS a beta-lactam (cephalexin or amoxicillin). 1

Essential Adjunctive Measures

• Elevate the scrotum to promote gravity drainage of edema – this hastens clinical improvement and is often neglected 1
• Examine interdigital toe spaces for tinea pedis, fissuring, or maceration, as these serve as portals of entry and increase recurrence risk 1
• Assess for predisposing conditions including diabetes, venous insufficiency, lymphedema, and chronic edema 1

Indications for Hospitalization and IV Therapy

Hospitalize and initiate IV antibiotics if:

• Systemic toxicity – fever, hypotension, altered mental status, or SIRS criteria 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1, 2
• Inability to tolerate oral medications or lack of outpatient follow-up 1

For hospitalized patients without MRSA risk factors, use cefazolin 1-2 g IV every 8 hours or nafcillin 2 g IV every 6 hours. 1 For severe infections with systemic toxicity or suspected necrotizing fasciitis, use vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours. 1

Critical Pitfalls to Avoid

• Do not delay surgical consultation if any signs of necrotizing infection are present – Fournier's gangrene progresses rapidly and requires immediate debridement 1, 2
• Do not reflexively add MRSA coverage without specific risk factors – this represents overtreatment and increases antibiotic resistance 1
• Do not use doxycycline as monotherapy – it lacks reliable activity against beta-hemolytic streptococci 1
• Do not extend antibiotics to 7-10 days based on residual erythema alone – some inflammation persists even after bacterial eradication 1

Mandatory Reassessment

Reassess within 24-48 hours to verify clinical response. 1 If the patient shows progression despite appropriate therapy, this indicates either resistant organisms or a deeper/different infection than initially recognized (such as early Fournier's gangrene). 1, 2 Treatment failure rates of 21% have been reported with some oral regimens, making close follow-up essential. 1