Outpatient Treatment of Uncomplicated Cellulitis
For typical uncomplicated cellulitis in the outpatient setting, prescribe oral cephalexin 500 mg every 6 hours (four times daily) for 5 days, stopping at 5 days if clinical improvement has occurred—MRSA coverage is unnecessary in 96% of cases. 1
First-Line Antibiotic Selection
Beta-lactam monotherapy is the standard of care for typical nonpurulent cellulitis, with a 96% success rate confirming that MRSA coverage is usually unnecessary. 1, 2
Recommended Oral Agents:
- Cephalexin 500 mg every 6 hours (preferred first-line) 1, 3
- Dicloxacillin 250-500 mg every 6 hours 1
- Amoxicillin 1
- Penicillin 1
- Amoxicillin-clavulanate 1
The FDA-approved dosing for cephalexin in adults ranges from 1-4 grams daily in divided doses, with 250 mg every 6 hours as the usual adult dose for skin infections. 3
Treatment Duration
Treat for exactly 5 days if clinical improvement occurs—extension is only warranted if symptoms have not improved within this timeframe. 1, 4 Traditional 7-14 day courses are no longer necessary for uncomplicated cases. 1 High-quality randomized controlled trial evidence demonstrates that 5-day courses achieve 98% clinical resolution with no relapse by 28 days, equivalent to 10-day courses. 5
Clinical Improvement Criteria (Stop at 5 Days If Present):
When to Add MRSA Coverage
Do NOT add MRSA coverage reflexively—it provides no additional benefit in typical cases. 1 Add MRSA-active antibiotics ONLY when specific risk factors are present:
MRSA Risk Factors Requiring Coverage:
- Penetrating trauma or injection drug use 1, 4
- Purulent drainage or exudate 1, 4
- Known MRSA colonization 1, 4
- Systemic inflammatory response syndrome (SIRS) 1, 4
- Failure to respond to beta-lactam therapy 1
MRSA-Active Regimens When Indicated:
- Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA, avoiding need for combination therapy) 1
- Trimethoprim-sulfamethoxazole (SMX-TMP) 1-2 double-strength tablets twice daily PLUS a beta-lactam 1
- Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1
Critical caveat: Doxycycline or SMX-TMP must NEVER be used as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1
Adjunctive Measures That Accelerate Recovery
- Elevate the affected extremity above heart level for at least 30 minutes three times daily to promote gravity drainage of edema and inflammatory substances 1, 4
- Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—treating these eradicates streptococcal colonization and reduces recurrent infection risk 1, 4
- Address predisposing conditions including venous insufficiency, lymphedema, chronic edema, and obesity 1, 4
When to Hospitalize
Admit for IV therapy if any of the following are present:
- Systemic inflammatory response syndrome (fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm) 1, 4
- Hypotension or hemodynamic instability 1
- Altered mental status or confusion 1
- Severe immunocompromise or neutropenia 1, 4
- Inability to tolerate oral medications 4
- Rapidly progressive infection despite appropriate outpatient therapy 4
- Concern for necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1
Common Pitfalls to Avoid
Do not reflexively add MRSA coverage simply because MRSA exists in your community—combination therapy with SMX-TMP plus cephalexin is no more efficacious than cephalexin alone in pure cellulitis without abscess, ulcer, or purulent drainage. 1
Do not extend treatment to 10-14 days based on tradition rather than evidence—this increases antibiotic resistance without improving outcomes in uncomplicated cases. 1
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