Recommended Antibiotic Treatment for Cellulitis
For typical uncomplicated cellulitis without purulent drainage, beta-lactam monotherapy with cephalexin 500 mg four times daily for 5 days is the standard of care and is successful in 96% of patients. 1, 2
First-Line Treatment Algorithm
For Nonpurulent Cellulitis (No Abscess, No Purulent Drainage)
Beta-lactam monotherapy is all you need. MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, and adding MRSA coverage provides no additional benefit. 1, 2
Recommended oral agents include:
- Cephalexin 500 mg four times daily (preferred first-line) 2
- Penicillin or amoxicillin (equally effective alternatives) 1, 2
- Dicloxacillin 250 mg every 6 hours for moderate infections 1
- Clindamycin 300-450 mg four times daily (for penicillin-allergic patients) 2
- Cefuroxime 500 mg twice daily (appropriate beta-lactam alternative) 1
Treatment duration: 5 days if clinical improvement occurs. Extend only if symptoms have not improved within this timeframe. 1, 2 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 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, 2
- Purulent drainage or exudate 3, 1
- Evidence of MRSA infection elsewhere or nasal MRSA colonization 1, 2
- Systemic inflammatory response syndrome (SIRS) 1, 2
- Failure to respond to beta-lactam therapy after 48-72 hours 3, 1
For outpatient MRSA coverage, choose ONE of these options: 3, 1
- Clindamycin 300-450 mg four times daily alone (covers both streptococci and MRSA, avoiding need for combination therapy) 3, 1, 2
- Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (e.g., cephalexin) 3, 1, 2
- Doxycycline 100 mg twice daily PLUS a beta-lactam 3, 1
Critical pitfall: Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis—they lack reliable activity against beta-hemolytic streptococci, which cause the majority of cases. 1 A randomized controlled trial demonstrated that adding TMP-SMX to cephalexin provided no benefit over cephalexin alone in patients with cellulitis without abscess. 4
Hospitalized Patients with Complicated Cellulitis
For hospitalized patients requiring IV therapy, vancomycin 15-20 mg/kg IV every 8-12 hours is the first-line agent. 3, 1 This recommendation has A-I level evidence. 3
Alternative IV options with equivalent efficacy include: 3, 1
- Linezolid 600 mg IV twice daily (A-I evidence) 3, 1
- Daptomycin 4 mg/kg IV once daily (A-I evidence) 3, 1
- Telavancin 10 mg/kg IV once daily (A-I evidence) 3, 1
- Clindamycin 600 mg IV three times daily (A-III evidence, only if local MRSA resistance <10%) 3, 1
For uncomplicated cellulitis requiring hospitalization: A beta-lactam antibiotic (e.g., IV cefazolin or oxacillin) may be considered with modification to MRSA-active therapy only if there is no clinical response. 3, 1 Beta-lactam monotherapy remains appropriate even in the inpatient setting if the cellulitis is nonpurulent and lacks MRSA risk factors, with a 96% success rate. 1
Treatment duration for hospitalized patients: 7-14 days, individualized based on clinical response. 3, 1
Severe Infections Requiring Broad-Spectrum Coverage
For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, broad-spectrum combination therapy is mandatory: 1, 2
- Vancomycin or linezolid PLUS piperacillin-tazobactam 1, 2
- Vancomycin plus a carbapenem (imipenem/meropenem) 2
- Vancomycin plus ceftriaxone and metronidazole 1
For documented group A streptococcal necrotizing fasciitis: Penicillin plus clindamycin is the specific recommended combination. 1, 2
Warning signs requiring emergent surgical consultation: 1
- Severe pain out of proportion to examination 1
- Skin anesthesia 1
- Rapid progression 1
- Gas in tissue 1
- Bullous changes 1
Pediatric Considerations
For hospitalized children with complicated cellulitis, vancomycin 15 mg/kg IV every 6 hours is the first-line agent. 3, 1
Alternative pediatric IV options: 3, 1
- Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (only if stable, no bacteremia, and local resistance <10%) 3, 1
- Linezolid 600 mg IV twice daily for children >12 years, or 10 mg/kg/dose IV every 8 hours for children <12 years 3, 1
Never use tetracyclines (including doxycycline) in children <8 years of age due to tooth discoloration and bone growth effects. 3, 1
Adjunctive Measures That Actually Matter
Elevation of the affected extremity hastens improvement by promoting drainage. 1, 2 This is not optional—it's a key intervention. 1
Examine and treat interdigital toe spaces for tinea pedis, as it serves as a portal of entry and addressing this reduces recurrence risk. 1, 2
Treat predisposing conditions including edema, obesity, eczema, venous insufficiency, and lymphedema. 1, 2
Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited. 1, 2
Common Pitfalls to Avoid
Do not reflexively add MRSA coverage simply because the patient is hospitalized or because MRSA prevalence is high in your institution. Beta-lactam therapy is successful in 96% of typical cellulitis cases. 1, 2
Do not continue ineffective antibiotics beyond 48 hours. Progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection than initially recognized. 1
Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics, not antibiotics alone. 1
Distinguish between cellulitis and purulent collections clinically: Cellulitis requires antibiotics as primary treatment, while purulent collections (furuncles, abscesses, septic bursitis) require drainage with antibiotics having a subsidiary role. 1
Hospitalization Criteria
Admit patients with any of the following: 1