I suspect cellulitis in an otherwise healthy adult; what is the most likely diagnosis and what evaluation and management should be undertaken?

Diagnosis and Initial Management of Suspected Cellulitis in a Healthy Adult

Most Likely Diagnosis

Cellulitis is the most likely diagnosis, defined as an acute bacterial infection of the deep dermis and subcutaneous tissue caused predominantly by β-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus. 1, 2

Clinical Diagnostic Criteria

Diagnose cellulitis clinically based on history and physical examination alone—laboratory tests and imaging are unnecessary for straightforward cases. 3

• History: Look for a preceding skin breach such as an insect bite (present in ~80% of cases), minor abrasion, or other portal of entry 1, 3
• Physical findings: Expanding erythema, warmth, tenderness, pain, and swelling with well-defined or poorly demarcated borders 3, 2, 4
• Systemic signs: Fever ≥38°C indicates systemic involvement and mandates immediate antibiotic therapy 3
• Document: Measure and mark the extent of erythema to track progression or improvement 1

Critical Red-Flag Assessment (Rule Out Necrotizing Infection)

Before initiating outpatient therapy, actively exclude necrotizing fasciitis by assessing for:

• Severe pain disproportionate to physical findings 1, 3
• Skin anesthesia, rapid progression despite antibiotics, or "wooden-hard" subcutaneous tissue 1, 3
• Bullous changes, subcutaneous gas, or skin necrosis 1
• Systemic toxicity: hypotension, altered mental status, or organ dysfunction 1

If any of these are present, obtain emergent surgical consultation and initiate vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours immediately. 1, 3

First-Line Antibiotic Therapy for Uncomplicated Cellulitis

Initiate beta-lactam monotherapy immediately—do not delay antibiotics to obtain imaging or laboratory studies. 3

Oral Regimen (Outpatient)

• Cephalexin 500 mg orally every 6 hours for 5 days 1, 3, 4
• Alternative: Dicloxacillin 250-500 mg orally every 6 hours for 5 days 1, 3

Beta-lactam monotherapy achieves 96% clinical success in typical non-purulent cellulitis, confirming that routine MRSA coverage is unnecessary. 1, 3

When to Add MRSA Coverage (and When NOT To)

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 3

• Purulent drainage or exudate 1, 3
• Penetrating trauma or injection drug use 1, 3
• Known MRSA colonization or prior MRSA infection 1, 3
• Systemic inflammatory response syndrome (beyond isolated fever) 1, 3
• Failure to respond to beta-lactam therapy after 48-72 hours 1, 3

For typical cellulitis following an insect bite without these factors, MRSA coverage represents overtreatment in ~96% of cases. 1, 3

MRSA-Active Regimens (When Indicated)

• Clindamycin 300-450 mg orally every 6 hours for 5 days (single-agent coverage for both streptococci and MRSA, but use only if local MRSA clindamycin resistance <10%) 1
• Alternative: TMP-SMX 1-2 double-strength tablets twice daily PLUS cephalexin 500 mg every 6 hours for 5 days 1
• Alternative: Doxycycline 100 mg twice daily PLUS cephalexin 500 mg every 6 hours for 5 days 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs (resolution of warmth/tenderness, decreasing erythema, defervescence); extend only if symptoms have not improved. 1, 3

High-quality randomized controlled trial evidence shows 5-day courses are as effective as 10-day courses for uncomplicated cellulitis—traditional 7-14 day regimens are unnecessary. 1

Hospitalization Criteria

Admit patients who meet any of the following criteria: 1, 3

• Systemic inflammatory response syndrome (fever >38°C, heart rate >90 bpm, respiratory rate >24/min) 1, 3
• Hypotension or hemodynamic instability 1
• Altered mental status or confusion 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1, 3

Inpatient IV Therapy

• Cefazolin 1-2 g IV every 8 hours for uncomplicated cellulitis requiring hospitalization without MRSA risk factors 1, 3
• Vancomycin 15-20 mg/kg IV every 8-12 hours for complicated cellulitis with MRSA risk factors (A-I evidence) 1

Essential Adjunctive Measures

• Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema 1, 3
• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration and treat if present to reduce recurrence risk 1, 3
• Address predisposing conditions: venous insufficiency, lymphedema, chronic edema, obesity, and eczema 1

Mandatory Reassessment

Re-evaluate patients within 24-48 hours to verify clinical response; oral regimens have reported failure rates of ~21% when response is inadequate. 1, 3

If no improvement after 48-72 hours of appropriate therapy, consider: 1

• Resistant organisms (MRSA)
• Undrained abscess (obtain ultrasound if uncertain)
• Deeper infection (necrotizing fasciitis, osteomyelitis)
• Alternative diagnosis (venous stasis dermatitis, contact dermatitis, DVT)

Common Pitfalls to Avoid

• Do NOT delay antibiotics to obtain imaging when clinical diagnosis is clear 3
• Do NOT add MRSA coverage reflexively for typical non-purulent cellulitis without specific risk factors 1, 3
• Do NOT use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they lack reliable streptococcal coverage 1
• Do NOT continue ineffective antibiotics beyond 48 hours if infection is progressing 1
• Do NOT delay surgical consultation if any signs of necrotizing infection are present 1, 3