What is the recommended treatment for a patient with cellulitis?

Treatment of Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy (such as cephalexin 500 mg four times daily or dicloxacillin 250-500 mg every 6 hours) for 5 days is the standard of care, with a 96% success rate. 1

First-Line Antibiotic Selection

For Uncomplicated Nonpurulent Cellulitis

• Beta-lactam monotherapy is the definitive treatment, as MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings 1, 2

• Recommended oral agents include:

  • Cephalexin 500 mg orally every 6 hours (four times daily) 1
  • Dicloxacillin 250-500 mg every 6 hours 1
  • Amoxicillin (standard dosing) 1
  • Penicillin V 250-500 mg four times daily 1
  • Amoxicillin-clavulanate 875/125 mg twice daily (particularly for bite-associated cellulitis) 1

• These agents provide excellent coverage against the primary pathogens: beta-hemolytic streptococci (especially Streptococcus pyogenes) and methicillin-sensitive Staphylococcus aureus 1, 2, 3

For Hospitalized Patients Requiring IV Therapy

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis requiring hospitalization 1
• Alternative IV options include nafcillin 2 g IV every 6 hours or oxacillin 2 g IV every 6 hours 1

Treatment Duration

Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1

• This 5-day duration is supported by high-quality randomized controlled trial evidence showing equivalence to 10-14 day courses 1
• Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1
• Common pitfall: Extending treatment to 10-14 days based on residual erythema alone is inappropriate, as some inflammation persists even after bacterial eradication 1

When to Add MRSA Coverage

Do NOT routinely add MRSA coverage for typical nonpurulent cellulitis. 1 MRSA coverage is appropriate only when specific risk factors are present:

MRSA Risk Factors Include:

• Penetrating trauma or injection drug use 1, 2
• 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:

For outpatient oral therapy:

• Clindamycin 300-450 mg orally every 6 hours (provides single-agent coverage for both streptococci and MRSA, avoiding need for combination therapy) 1
  • Use only if local MRSA clindamycin resistance rates are <10% 1
• Trimethoprim-sulfamethoxazole (SMX-TMP) 1-2 double-strength tablets twice daily PLUS a beta-lactam (such as cephalexin) 1
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam 1
  • Never use doxycycline as monotherapy for typical cellulitis, as it lacks reliable activity against beta-hemolytic streptococci 1

For hospitalized patients:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1
• Alternative IV agents include:
  • 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 every 8 hours (if local resistance <10%, A-III evidence) 1

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. 1

Indications for Severe Infection Protocol:

• Fever, hypotension, tachycardia, or altered mental status 1
• Severe pain out of proportion to examination 1
• Skin anesthesia, rapid progression, or bullous changes 1
• Gas in tissue or "wooden-hard" subcutaneous tissues 1

Recommended IV Combination Regimens:

• Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS piperacillin-tazobactam 3.375-4.5 g IV every 6 hours 1
• Alternative: Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 1
• Alternative: Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 1
• Alternative: Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 1

Treatment duration for severe infections: 7-14 days, guided by clinical response 1

Special Populations and Situations

Diabetic Foot Cellulitis

• Requires broader coverage and longer duration due to polymicrobial nature 1
• For mild infections: Dicloxacillin, clindamycin, cephalexin, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, or levofloxacin 1
• For moderate infections: Amoxicillin-clavulanate, levofloxacin, ceftriaxone, ampicillin-sulbactam, or ertapenem 1
• For severe infections: Piperacillin-tazobactam, imipenem-cilastatin, or vancomycin plus ceftazidime with or without metronidazole 1

Bite-Associated Cellulitis

• Amoxicillin-clavulanate 875/125 mg twice daily as monotherapy provides single-agent coverage for polymicrobial oral flora 1

Penicillin/Cephalosporin Allergy

• Clindamycin 300-450 mg orally every 6 hours is the optimal choice (covers both streptococci and MRSA) 1
• Alternative: Levofloxacin 500 mg daily (reserve for beta-lactam allergies; lacks reliable MRSA coverage) 1
• For hospitalized patients: Vancomycin 15-20 mg/kg IV every 8-12 hours or linezolid 600 mg IV twice daily 1

Essential Adjunctive Measures

These interventions are critical and often neglected:

• Elevation of 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 predisposing conditions: venous insufficiency, lymphedema, chronic edema, obesity, and eczema 1
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) 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 or hemodynamic instability 1
• Altered mental status or confusion 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1

Prevention of Recurrent Cellulitis

• Annual recurrence rates are 8-20% in patients with previous cellulitis 1
• For patients with 3-4 episodes per year despite treating predisposing factors, consider prophylactic antibiotics:
  • Penicillin V 250 mg orally twice daily 1
  • Erythromycin 250 mg orally twice daily 1
  • Intramuscular benzathine penicillin 4

Critical Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized or because MRSA prevalence is high in your institution 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 extend treatment beyond 5 days based solely on residual erythema without other signs of active infection 1
• Do not delay surgical consultation if any signs of necrotizing infection are present, as these progress rapidly and require debridement 1
• Do not continue ineffective antibiotics beyond 48 hours; progression despite appropriate therapy indicates resistant organisms or a different/deeper infection 1