Outpatient Cellulitis Management
First-Line Antibiotic Therapy
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, and MRSA coverage should NOT be added routinely. 1
Recommended Oral Beta-Lactam Options:
- Cephalexin 500 mg orally four times daily 1
- Dicloxacillin 250-500 mg orally every 6 hours 1
- Amoxicillin or amoxicillin-clavulanate 1
- Clindamycin 300-450 mg orally three times daily (covers both streptococci and MRSA if local resistance <10%) 1
The rationale is straightforward: most cellulitis is caused by β-hemolytic streptococci and methicillin-sensitive S. aureus, not MRSA, even in high-prevalence settings. 1, 2 MRSA is an uncommon cause of typical nonpurulent cellulitis. 1
Treatment Duration
Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1
Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1 This shorter duration is supported by high-quality evidence and reduces unnecessary antibiotic exposure.
When to Add MRSA Coverage
Add MRSA-active antibiotics ONLY when specific risk factors are present: 1
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 1
- Known MRSA colonization or evidence of MRSA infection elsewhere 1
- Systemic inflammatory response syndrome (SIRS) 1
- Failure to respond to beta-lactam therapy after 48-72 hours 1
MRSA-Active Regimens for Outpatients:
- Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (e.g., cephalexin) 1
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1
- Clindamycin monotherapy 300-450 mg orally three times daily (provides coverage for both streptococci and MRSA, avoiding need for combination therapy) 1
Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as their activity against β-hemolytic streptococci is unreliable. 1 They must be combined with a beta-lactam for adequate streptococcal coverage.
Adjunctive Measures
- Elevate the affected extremity to promote drainage and hasten improvement 1
- Treat predisposing conditions: tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, eczema, and obesity 1
- Consider systemic corticosteroids (e.g., prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1
Reassessment and Treatment Failure
Mandatory reassessment at 48-72 hours is essential to verify clinical response. 1 If cellulitis is spreading despite appropriate antibiotics:
- Evaluate for necrotizing fasciitis warning signs: severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, systemic toxicity, or bullous changes 1
- Reassess for MRSA risk factors or misdiagnosis 1
- Switch to MRSA-active therapy (vancomycin or linezolid) if MRSA is suspected or systemic toxicity is present 1
- Obtain emergent surgical consultation if necrotizing infection is suspected 1
Do not continue ineffective antibiotics beyond 48 hours. 1
Indications for Hospitalization
Hospitalize if any of the following are present: 1
- Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1
- Severe immunocompromise or neutropenia 1
- Rapid progression or suspected necrotizing fasciitis 1
- Failure of outpatient therapy with worsening despite appropriate antibiotics 1
Special Considerations
Bite-Associated Cellulitis:
- Amoxicillin-clavulanate 875/125 mg orally twice daily provides single-agent coverage for both streptococci and common oral flora from human or animal bites 1
Purulent Cellulitis vs. Abscess:
- Abscesses require incision and drainage as primary treatment, with antibiotics playing a subsidiary role 1
- If there is clinical uncertainty about an abscess, assess with ultrasound 1
- Furuncles, abscesses, and septic bursitis are purulent collections requiring drainage, not antibiotics alone 1
Pediatric Considerations:
- Cephalexin is the most commonly prescribed oral antibiotic for pediatric cellulitis 3
- Oral antibiotics are effective and require fewer visits and less time in the ED compared with IV treatment 3
- Doxycycline should never be used in children under 8 years due to tooth discoloration and bone growth effects 1
Common Pitfalls to Avoid
- Do not reflexively add MRSA coverage simply because the patient presents to the ED or has "severe-looking" cellulitis—MRSA is uncommon in typical nonpurulent cellulitis 1
- 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—progression despite appropriate therapy indicates resistant organisms or a different/deeper infection 1
- Do not delay surgical consultation if any signs of necrotizing infection are present—these infections progress rapidly and require debridement 1