Best Antibiotic for Cellulitis
For uncomplicated cellulitis, cephalexin 500 mg four times daily for 5-6 days is the first-line treatment, targeting β-hemolytic streptococci which cause the vast majority of typical cellulitis cases. 1, 2
First-Line Treatment Algorithm
For Typical (Nonpurulent) Cellulitis
- Cephalexin 500 mg four times daily is the preferred first-line agent 1, 2
- Alternative β-lactams include penicillin or amoxicillin, all targeting streptococci 1, 2
- For penicillin-allergic patients: clindamycin 300-450 mg four times daily 2, 3
- Treatment duration: 5-6 days is as effective as 10 days, with extension only if no improvement occurs 1, 2
The rationale is straightforward: β-hemolytic streptococci cause the overwhelming majority of nonpurulent cellulitis, and β-lactam therapy succeeds in 96% of typical cases 4. MRSA is an unusual cause of cellulitis without purulent drainage 4.
When to Add MRSA Coverage
Reserve MRSA-active antibiotics only for cellulitis with specific risk factors: 1, 2
- Penetrating trauma
- Evidence of MRSA infection elsewhere or nasal colonization
- Injection drug use
- Systemic inflammatory response syndrome (SIRS)
- Purulent drainage (purulent cellulitis)
For MRSA coverage when indicated:
- Clindamycin 300-450 mg four times daily (covers both streptococci and MRSA) 1, 2
- Alternatively: TMP-SMX 1-2 double-strength tablets twice daily PLUS a β-lactam (not TMP-SMX alone, as its activity against streptococci is unreliable) 1, 2
Evidence Against Routine MRSA Coverage
Two high-quality randomized controlled trials definitively show that adding MRSA coverage to standard therapy provides no benefit for uncomplicated cellulitis:
- A 2017 multicenter trial of 496 patients found cephalexin plus TMP-SMX achieved 83.5% cure versus 85.5% with cephalexin alone (no significant difference) 5
- A 2013 trial of 146 patients similarly showed 85% cure with combination therapy versus 82% with cephalexin alone 6
This evidence strongly supports avoiding unnecessary MRSA coverage for typical cellulitis. 5, 6
Severe or Complicated Cellulitis Requiring Hospitalization
Hospitalize patients with: 1
- SIRS or systemic toxicity
- Altered mental status or hemodynamic instability
- Concern for deeper/necrotizing infection
- Severe immunocompromise
- Failure of outpatient treatment
Intravenous options for hospitalized patients: 1
- Vancomycin 15-20 mg/kg IV every 8-12 hours
- For severe infections with concern for gram-negatives: vancomycin plus piperacillin-tazobactam or a carbapenem 1
- Alternative MRSA-active agents: linezolid 600 mg IV twice daily, daptomycin 4 mg/kg IV daily 1, 7
Critical Adjunctive Measures
Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema 1, 2
Address predisposing conditions: 1, 2
- Examine interdigital toe spaces for tinea pedis—treating fissuring and maceration reduces recurrence 1
- Manage venous insufficiency, lymphedema, obesity, eczema 1
Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults with cellulitis 1, 2
Monitoring and Treatment Extension
- Expect clinical improvement within 48-72 hours of starting antibiotics 2
- Extend treatment beyond 5 days only if infection has not improved 1, 2
- Blood cultures are not routinely recommended for uncomplicated cellulitis 1
Common Pitfalls to Avoid
Overuse of broad-spectrum antibiotics: The single most common error is prescribing MRSA-active antibiotics for typical cellulitis without risk factors 2, 4, 8
Prolonged antibiotic courses: Continuing antibiotics beyond 5-6 days when clinical improvement has occurred is unnecessary and increases adverse effects 1, 2
Failure to address underlying conditions: Not treating tinea pedis, venous stasis, or other predisposing factors leads to recurrent cellulitis 1, 2
Misdiagnosis: Many conditions mimic cellulitis (venous stasis dermatitis, contact dermatitis, eczema)—cellulitis presents with acute onset of erythema, warmth, swelling, and tenderness 4, 8
budget:token_budget Tokens used this turn: 4426 Tokens remaining: 195574