What is the recommended antibiotic and dosage for treating cellulitis?

Antibiotic and Dosage for Cellulitis

For typical uncomplicated cellulitis, use cephalexin 500 mg orally four times daily for 5 days, as beta-lactam monotherapy is successful in 96% of cases and MRSA coverage is unnecessary. 1, 2

First-Line Treatment Algorithm

Standard Nonpurulent Cellulitis (No MRSA Risk Factors)

Beta-lactam monotherapy is the standard of care:

• Cephalexin 500 mg orally four times daily for 5 days is the preferred first-line agent 1, 2
• Alternative beta-lactams include:
  • Dicloxacillin 250-500 mg orally every 6 hours for 5 days 1, 2
  • Amoxicillin or penicillin (equally effective alternatives) 1, 2
  • Cefuroxime 500 mg orally twice daily for 5 days 1
  • Amoxicillin-clavulanate 875/125 mg twice daily (particularly for bite-associated cellulitis) 1

For penicillin-allergic patients:

• Clindamycin 300-450 mg orally four times daily for 5 days 1, 2

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 2, 3 Traditional 7-14 day courses are no longer necessary for uncomplicated cases, as 5 days is equally effective as 10 days. 1, 3

When to Add MRSA Coverage

Add MRSA-active antibiotics ONLY when specific risk factors are present: 1, 2

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Evidence of MRSA infection elsewhere or nasal MRSA colonization 1, 2
• Systemic inflammatory response syndrome (SIRS) 1, 2
• Failed beta-lactam therapy 1

MRSA-active regimens for outpatients:

• Clindamycin 300-450 mg orally four times daily for 5 days (covers both streptococci and MRSA, avoiding need for combination therapy) 1, 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS cephalexin (TMP-SMX alone lacks reliable streptococcal coverage) 1, 2
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (doxycycline alone is inadequate for streptococci) 1, 4

Critical Pitfall: Never Use Doxycycline or TMP-SMX as Monotherapy

Doxycycline and TMP-SMX must be combined with a beta-lactam when treating typical nonpurulent cellulitis, as tetracyclines and sulfonamides lack reliable activity against beta-hemolytic streptococci. 1 Using these agents alone for typical cellulitis will result in treatment failure due to inadequate streptococcal coverage. 1

Inpatient/IV Therapy

For hospitalized patients requiring IV therapy:

• Cefazolin 1-2 g IV every 8 hours for uncomplicated cellulitis without MRSA risk factors 1
• Vancomycin 15-20 mg/kg IV every 8-12 hours for MRSA coverage (A-I evidence) 1, 2
• Alternative MRSA-active IV agents:
  • Linezolid 600 mg IV twice daily (A-I evidence) 1, 2
  • Daptomycin 4 mg/kg IV once daily (A-I evidence) 1, 2
  • Clindamycin 600 mg IV three times daily (only if local MRSA resistance <10%) 1

Transition to oral therapy once clinical improvement is demonstrated, typically after minimum 4 days of IV treatment. 1 Oral options include cephalexin, dicloxacillin, or clindamycin. 1

Severe/Complicated Cellulitis

For patients with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, use broad-spectrum combination therapy: 1, 2

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

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

Adjunctive Measures

Non-antibiotic interventions that hasten improvement:

• Elevate the affected extremity to promote drainage 1, 2
• Examine and treat interdigital toe spaces for tinea pedis (portal of entry) 1, 2
• Address predisposing conditions: edema, venous insufficiency, lymphedema, obesity 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults 1, 2

Hospitalization Criteria

Admit patients with any of the following: 1, 2

• Systemic inflammatory response syndrome (SIRS), fever, hypotension, or altered mental status 1, 2
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing fasciitis or deeper infection 2
• Failed outpatient therapy 2

Key Evidence Supporting Beta-Lactam Monotherapy

The recommendation for beta-lactam monotherapy is based on strong evidence showing that MRSA is an uncommon cause of typical cellulitis, even in high-prevalence settings. 1, 2 Beta-hemolytic streptococci and methicillin-sensitive S. aureus cause the vast majority of cases, with beta-lactam therapy successful in 96% of patients. 1, 2 Adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases without specific risk factors. 1

Reassess in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens. 1 If cellulitis is spreading despite appropriate antibiotics, evaluate for necrotizing fasciitis, MRSA risk factors, or misdiagnosis, and obtain emergent surgical consultation if necrotizing infection is suspected. 1