Cellulitis Treatment
First-Line Antibiotic Therapy
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, achieving 96% clinical success because MRSA is an uncommon cause even in high-prevalence settings. 1
Recommended Oral Regimens (Choose One)
- Cephalexin 500 mg orally every 6 hours 1
- Dicloxacillin 250-500 mg orally every 6 hours 1
- Amoxicillin (standard dosing) 1
- Penicillin V 250-500 mg orally four times daily 1
Treatment Duration
Treat for exactly 5 days if clinical improvement occurs (reduced warmth, tenderness, improving erythema, no fever); extend only if symptoms have not improved. 1 High-quality randomized controlled trial evidence confirms 5-day courses are as effective as 10-day courses for uncomplicated cellulitis. 1 Traditional 7-14 day regimens are unnecessary. 1
When to Add MRSA Coverage
Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 2
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate visible at the infection site 1
- Known MRSA colonization or prior MRSA infection 1
- Systemic inflammatory response syndrome (SIRS: fever >38°C, tachycardia >90 bpm, tachypnea >24 breaths/min) 1
- Failure to respond to beta-lactam therapy after 48-72 hours 1
In the absence of these factors, adding MRSA coverage provides no benefit and represents overtreatment. 1
MRSA-Active Regimens (When Risk Factors Present)
Purulent Cellulitis – Monotherapy Options
- Clindamycin 300-450 mg orally every 6 hours for 5 days – provides single-agent coverage for both streptococci and MRSA, but use only if local MRSA clindamycin resistance is <10% 1, 2
Non-Purulent Cellulitis Requiring MRSA Coverage – Combination Therapy
Doxycycline or TMP-SMX MUST be combined with a beta-lactam because they lack reliable streptococcal activity: 1, 2
- Doxycycline 100 mg orally twice daily PLUS cephalexin 500 mg four times daily for 5 days 1
- Trimethoprim-sulfamethoxazole 1-2 double-strength tablets twice daily PLUS cephalexin or amoxicillin for 5 days 1, 2
Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis—this misses streptococcal pathogens in ~96% of cases. 1
Penicillin Allergy Management
Non-Immediate Hypersensitivity (e.g., Rash)
- Cephalexin remains acceptable because cross-reactivity is only 2-4% 1
- Avoid cephalexin only in confirmed immediate-type amoxicillin allergy (identical R1 side chains) 1
True Penicillin Allergy
- Clindamycin 300-450 mg orally every 6 hours (if local MRSA resistance <10%) 1
- Alternative: Doxycycline 100 mg twice daily PLUS a beta-lactam (if beta-lactam can be tolerated) 1
Intravenous Therapy for Hospitalized Patients
Indications for Hospitalization
Admit patients with: 1
- Systemic inflammatory response syndrome (fever, tachycardia, hypotension, altered mental status)
- Signs of necrotizing infection (severe pain out of proportion, skin anesthesia, rapid progression, "wooden-hard" tissue, gas or bullae)
- Severe immunocompromise or neutropenia
- Failure of outpatient therapy after 24-48 hours
IV Regimens Without MRSA Risk Factors
- Cefazolin 1-2 g IV every 8 hours (preferred) 1
- Nafcillin or oxacillin 2 g IV every 6 hours (alternatives) 1
IV Regimens for MRSA Coverage
First-line (A-I evidence): 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours (target trough 15-20 mg/L)
- Linezolid 600 mg IV twice daily
- Daptomycin 4 mg/kg IV once daily
Alternative (A-III evidence): 1
- Clindamycin 600 mg IV every 8 hours (only if local MRSA resistance <10%)
Duration for complicated infections: 7-14 days, individualized by clinical response. 1
Severe Cellulitis with Systemic Toxicity
For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required: 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
- Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
- Alternative: Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1
For documented group A streptococcal necrotizing fasciitis: penicillin plus clindamycin. 1
Do not delay surgical consultation when any signs of necrotizing infection are present—these infections progress rapidly and require debridement. 1
Adjunctive Measures
Elevation of the affected extremity above heart level for at least 30 minutes three times daily hastens improvement by promoting gravity drainage of edema. 1
Treat predisposing conditions: 1
- Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration
- Address venous insufficiency, lymphedema, chronic edema
- Treat eczema and obesity-related skin breakdown
Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1 Avoid corticosteroids in diabetic patients—diabetes is an absolute contraindication. 1
Pediatric Dosing
Oral Therapy
- Cephalexin 25-50 mg/kg/day divided every 6 hours 1
- Clindamycin 10-13 mg/kg/dose every 6-8 hours (max 40 mg/kg/day; only if local MRSA resistance <10%) 1
- TMP-SMX 4-6 mg/kg/dose (TMP component) twice daily PLUS a beta-lactam 1
- Doxycycline 2 mg/kg/dose twice daily (max 100 mg) PLUS a beta-lactam – contraindicated in children <8 years due to tooth discoloration and bone growth effects 1
IV Therapy for Hospitalized Children
- Vancomycin 15 mg/kg IV every 6 hours (first-line, A-II evidence) 1
- Clindamycin 10-13 mg/kg IV every 6-8 hours (if stable, no bacteremia, local resistance <10%) 1
- Linezolid 10 mg/kg IV every 8 hours (<12 years) or 600 mg IV twice daily (≥12 years) 1
Hospitalize children <6 months old with moderate-to-severe disease. 1
Critical Pitfalls to Avoid
Do not add MRSA coverage reflexively to all cellulitis cases—MRSA is uncommon in typical non-purulent cellulitis even in high-prevalence settings. 1, 3
Do not use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they lack reliable activity against beta-hemolytic streptococci. 1, 2
Do not automatically extend therapy to 7-10 days based on residual erythema alone—inflammation can persist for 1-2 weeks after bacterial eradication. 1
Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or deeper infection. 1
Do not delay surgical consultation if necrotizing infection is suspected—severe pain out of proportion, rapid progression, bullae, or gas in tissue mandate emergent evaluation. 1
Reassess patients within 24-48 hours to verify clinical response—treatment failure rates of 21% have been reported with some oral regimens. 1