Antibiotics for Cellulitis
First-Line Treatment for Uncomplicated Cellulitis
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, and MRSA coverage is unnecessary in most cases. 1
- Recommended oral beta-lactam agents include cephalexin 500 mg every 6 hours, dicloxacillin 250-500 mg every 6 hours, amoxicillin, or penicillin V 250-500 mg four times daily. 1
- Treatment duration is 5 days if clinical improvement occurs—extend only if symptoms have not improved within this timeframe. 1, 2
- Beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus are the primary pathogens in typical nonpurulent cellulitis. 3, 4
Dosing Specifics from FDA Labels
- Dicloxacillin: 250 mg every 6 hours for mild-to-moderate infections, 500 mg every 6 hours for severe infections, taken on an empty stomach at least 1 hour before or 2 hours after meals. 5
- Amoxicillin-clavulanate (Augmentin): 875/125 mg twice daily for more severe infections or respiratory tract involvement, taken at the start of meals to enhance absorption and minimize GI intolerance. 6
When to Add MRSA Coverage
Add MRSA-active antibiotics ONLY when specific risk factors are present—do not reflexively add coverage simply because the patient is hospitalized or because MRSA prevalence is high in your region. 1
MRSA Risk Factors Requiring Coverage:
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 3, 1
- Known MRSA colonization or prior MRSA infection 1
- Systemic inflammatory response syndrome (SIRS) with fever, tachycardia, or altered mental status 1
- Failure to respond to beta-lactam therapy after 48-72 hours 3
MRSA-Active Oral Regimens:
- Clindamycin 300-450 mg orally every 6 hours provides single-agent coverage for both streptococci and MRSA (use only if local resistance <10%). 3, 1
- Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily PLUS a beta-lactam (e.g., cephalexin or amoxicillin). 3, 1
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam—never use doxycycline as monotherapy due to unreliable streptococcal coverage. 3, 1
Critical caveat: Combination therapy with cephalexin plus TMP-SMX is no more effective than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage. 7, 8
Intravenous Antibiotics for Hospitalized Patients
Uncomplicated Cellulitis Requiring Hospitalization (No MRSA Risk Factors):
- Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for hospitalized patients with nonpurulent cellulitis. 1
- Oxacillin 2 g IV every 6 hours or nafcillin 2 g IV every 6 hours are alternatives. 1
Complicated Cellulitis or MRSA Coverage Needed:
- Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line for hospitalized adults with complicated cellulitis (A-I evidence). 3, 1
- Alternative IV agents with equivalent efficacy include linezolid 600 mg IV twice daily (A-I), daptomycin 4 mg/kg IV once daily (A-I), or clindamycin 600 mg IV three times daily (A-III, only if local resistance <10%). 3, 1
- Treatment duration for complicated infections is 7-14 days, individualized based on clinical response. 3
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 immediately. 9
- Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours is the recommended empiric regimen. 1, 9
- Alternative combinations include vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours or imipenem 500 mg IV every 6 hours), or vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours. 1, 9
- This combination provides coverage against MRSA, beta-hemolytic streptococci, gram-negative organisms, and anaerobes. 9
- Treatment duration is 7-14 days for severe infections with systemic signs. 9
Warning Signs Requiring Emergent Surgical Consultation:
- Severe pain out of proportion to examination 1
- Skin anesthesia, rapid progression, gas in tissue, or bullous changes 1
- "Wooden-hard" subcutaneous tissues suggesting necrotizing infection 1
Common Pitfalls to Avoid
- Do not use doxycycline or TMP-SMX as monotherapy for typical cellulitis—their activity against beta-hemolytic streptococci is unreliable. 1
- Do not routinely add MRSA coverage for typical nonpurulent cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance. 1
- Do not extend treatment to 10-14 days based on residual erythema alone—some inflammation persists even after bacterial eradication. 1
- Do not delay broad-spectrum antibiotics in patients with severe cellulitis and systemic signs—this is a medical emergency. 9
- Do not substitute two 250 mg/125 mg amoxicillin-clavulanate tablets for one 500 mg/125 mg tablet—they contain different amounts of clavulanic acid and are not equivalent. 6
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
- Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—treating these eradicates colonization and reduces recurrent infection risk. 1
- Address underlying venous insufficiency, lymphedema, and chronic edema with compression stockings once acute infection resolves. 1
- Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults to reduce inflammation, though evidence is limited. 1