What is the recommended treatment for cellulitis?

Treatment of Cellulitis

First-Line Antibiotic Therapy

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis and achieves clinical success in 96% of patients—MRSA coverage is unnecessary in most cases. 1

Recommended Oral Agents for Outpatient Treatment

• Cephalexin (500 mg four times daily), dicloxacillin (250-500 mg four times daily), amoxicillin, or penicillin are appropriate first-line choices for nonpurulent cellulitis 1, 2
• Clindamycin (300-450 mg four times daily) provides coverage for both streptococci and MRSA, eliminating the need for combination therapy when MRSA coverage is indicated 1
• Amoxicillin-clavulanate (Augmentin 875/125 mg twice daily) is specifically recommended for bite-associated cellulitis (human or animal) as it provides single-agent polymicrobial coverage 1

Treatment Duration

• Treat for 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

MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings—do not add MRSA coverage reflexively. 1 Add MRSA-active antibiotics ONLY when specific risk factors are present:

• Penetrating trauma or injection drug use 1
• Purulent drainage or exudate 1
• Known MRSA colonization or prior MRSA infection 1
• Systemic inflammatory response syndrome (SIRS) 1
• Failure to respond to beta-lactam therapy after 48 hours 1

MRSA-Active Regimens

• Clindamycin monotherapy (300-450 mg four times daily) covers both streptococci and MRSA if local resistance is <10% 1
• Trimethoprim-sulfamethoxazole PLUS a beta-lactam (cephalexin) for combination coverage 1
• Doxycycline (100 mg twice daily) PLUS a beta-lactam—never use doxycycline as monotherapy due to unreliable streptococcal activity 1

Critical pitfall: Adding trimethoprim-sulfamethoxazole to cephalexin provides no additional benefit in pure cellulitis without abscess, ulcer, or purulent drainage 1, 3

Inpatient IV Antibiotic Selection

For Complicated Cellulitis Requiring Hospitalization

Vancomycin (15-20 mg/kg IV every 8-12 hours) is first-line for hospitalized patients with complicated cellulitis (A-I evidence) 1

Alternative IV agents with equivalent efficacy:

• Linezolid 600 mg IV twice daily (A-I evidence) 1
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 1
• Clindamycin 600 mg IV three times daily if local MRSA resistance <10% (A-III evidence) 1

For uncomplicated cellulitis requiring hospitalization: Beta-lactam monotherapy with cefazolin (1-2 g IV every 8 hours) or oxacillin remains appropriate if the cellulitis is nonpurulent and lacks MRSA risk factors 1

For Severe Cellulitis with Systemic Toxicity

Broad-spectrum combination therapy is mandatory for patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis. 1

Recommended IV combinations:

• Vancomycin or linezolid PLUS piperacillin-tazobactam (3.375-4.5 g IV every 6 hours) 1
• Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
• 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 is the specific recommended combination 1

Transition to Oral Therapy

• Transition to oral antibiotics (cephalexin, dicloxacillin, or clindamycin) once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment 1
• Continue for a total of 5 days if improvement occurs 1

Adjunctive Measures

• Elevate the affected extremity to promote gravity drainage of edema and inflammatory substances 1, 2
• Treat predisposing conditions: tinea pedis, toe web abnormalities, venous insufficiency, lymphedema, eczema, and obesity 1, 2
• Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1

Indications for Hospitalization

Hospitalize if any of the following are present:

• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1
• Hypotension, altered mental status, or confusion 1
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing infection or deeper infection 2
• Failure of outpatient treatment 2

Warning Signs of Necrotizing Fasciitis

Obtain emergent surgical consultation if any of these are present:

• Severe pain out of proportion to examination 1
• Skin anesthesia or bullous changes 1
• Rapid progression or gas in tissue 1
• Systemic toxicity 1

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical cellulitis without specific risk factors—this represents overtreatment and increases antibiotic resistance 1
• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1
• Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates either resistant organisms or a deeper/different infection 1
• Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics 1

Prevention of Recurrence

• Identify and treat predisposing conditions (edema, venous insufficiency, toe web abnormalities) at initial diagnosis 2, 4
• For patients with 3-4 episodes per year despite treatment of predisposing factors, consider prophylactic antibiotics: oral penicillin, erythromycin, or intramuscular benzathine penicillin 2