What is the recommended treatment for cellulitis?

Treatment for Cellulitis

For typical uncomplicated cellulitis, use beta-lactam monotherapy (such as cephalexin 500 mg four times daily or dicloxacillin 250-500 mg every 6 hours) for 5 days if clinical improvement occurs, extending only if symptoms have not improved. 1, 2

First-Line Antibiotic Selection

Outpatient Oral Therapy for Uncomplicated Cellulitis

• Beta-lactam monotherapy is the standard of care and achieves success in 96% of patients with typical nonpurulent cellulitis. 1, 2, 3

• Recommended oral agents include: 1, 2

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

• For penicillin-allergic patients, clindamycin 300-450 mg orally four times daily provides single-agent coverage for both streptococci and MRSA, eliminating the need for combination therapy. 1, 2

Inpatient IV Therapy

• For hospitalized patients with uncomplicated cellulitis requiring IV therapy, cefazolin 1-2 g IV every 8 hours is the preferred beta-lactam. 1, 2

• Alternative IV beta-lactams include nafcillin or oxacillin 2 g IV every 6 hours. 1, 2

• Patients can transition to oral antibiotics once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment. 4

Treatment Duration

• Treat for exactly 5 days if clinical improvement has occurred; extend only if symptoms have not improved within this timeframe. 1, 2

• This represents a significant departure from traditional 7-14 day courses, which are no longer necessary for uncomplicated cases. 1

• For severe or complicated infections requiring hospitalization, 7-14 days of therapy may be appropriate, guided by clinical response. 1, 2

When to Add MRSA Coverage

MRSA coverage is NOT routinely necessary for typical cellulitis, as MRSA is an uncommon cause even in high-prevalence settings. 1, 2, 3

Specific Indications for MRSA Coverage

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

• Penetrating trauma or injection drug use
• Purulent drainage or exudate
• Evidence of MRSA infection elsewhere or nasal MRSA colonization
• Systemic inflammatory response syndrome (SIRS)
• Athletes, children in daycare, men who have sex with men, prisoners, military recruits, or long-term care facility residents 3

MRSA-Active Regimens

For outpatient therapy requiring MRSA coverage: 1, 2

• Clindamycin 300-450 mg orally four times daily (monotherapy) - covers both streptococci and MRSA, but only use if local clindamycin resistance rates are <10%
• Trimethoprim-sulfamethoxazole (SMX-TMP) PLUS a beta-lactam (combination required)
• Doxycycline 100 mg orally twice daily PLUS a beta-lactam (combination required)

Critical caveat: Never use doxycycline or SMX-TMP as monotherapy for cellulitis, as their activity against beta-hemolytic streptococci is unreliable. 1, 2

For hospitalized patients requiring MRSA coverage: 1, 2

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence)
• Linezolid 600 mg IV twice daily (A-I evidence)
• Daptomycin 4 mg/kg IV once daily (A-I evidence) 4
• Clindamycin 600 mg IV every 8 hours (only if local resistance <10%)

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. 1, 2

Indications for Hospitalization and Aggressive Therapy

Hospitalize immediately if any of the following are present: 1, 2

• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm
• Hypotension or hemodynamic instability
• Altered mental status or confusion
• Severe immunocompromise or neutropenia
• Concern for deeper or necrotizing infection (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes)

Empiric Combination Regimens for Severe Infection

Vancomycin 15-20 mg/kg IV every 8-12 hours PLUS one of the following: 1, 2

• Piperacillin-tazobactam 3.375-4.5 g IV every 6 hours (preferred)
• A carbapenem (meropenem 1 g IV every 8 hours)
• Ceftriaxone 2 g IV daily plus metronidazole 500 mg IV every 8 hours

For documented group A streptococcal necrotizing fasciitis specifically, use penicillin plus clindamycin. 2

• Treatment duration for severe infections is 7-14 days, guided by clinical response and source control. 1, 2

Essential Adjunctive Measures

These non-antibiotic interventions are critical and often neglected: 1, 2

• Elevation of the affected extremity above heart level for at least 30 minutes three times daily - promotes gravity drainage of edema and inflammatory substances, hastening improvement 1, 2

• Examine interdigital toe spaces carefully for tinea pedis, fissuring, scaling, or maceration - treating these eradicates bacterial colonization and reduces recurrent infection risk 1, 2, 5

• Address predisposing conditions: 1, 2, 5

  • Treat tinea pedis aggressively
  • Manage venous insufficiency with compression stockings (once acute infection resolves)
  • Reduce lymphedema through elevation, compression, or diuretic therapy if appropriate
  • Keep skin well hydrated with emollients
  • Treat venous eczema and other chronic skin conditions

• Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults to reduce inflammation, though evidence is limited. 1, 2

Prevention of Recurrent Cellulitis

Each attack of cellulitis causes lymphatic inflammation and possibly permanent damage, with annual recurrence rates of 8-20% in patients with previous episodes. 1, 6

Prophylactic Antibiotics

For patients with 3-4 episodes per year despite optimal management of predisposing factors, strongly consider prophylactic antibiotics: 1, 6

• Monthly intramuscular benzathine penicillin injections, OR
• Oral penicillin V 250 mg twice daily, OR
• Oral erythromycin 250 mg twice daily (if penicillin-allergic, though macrolide resistance is rising)

Pediatric Dosing Considerations

For hospitalized children with complicated cellulitis: 1, 2

• Vancomycin 15 mg/kg IV every 6 hours (first-line)
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if stable, no bacteremia, and local resistance <10%)
• Linezolid 600 mg IV twice daily for children >12 years, or 10 mg/kg/dose IV every 8 hours for children <12 years

For outpatient pediatric cellulitis requiring MRSA coverage, doxycycline 2 mg/kg/dose orally every 12 hours can be used in children over 8 years, but never in children under 8 years due to tooth discoloration and bone growth effects. 1

Common Pitfalls to Avoid

• Do not reflexively add MRSA coverage simply because the patient is hospitalized - beta-lactam monotherapy remains appropriate for typical cellulitis even in the inpatient setting if no specific MRSA risk factors are present 1, 2

• 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

• Do not delay surgical consultation if any signs of necrotizing infection are present - these infections progress rapidly and require debridement 1, 2

• Do not use doxycycline or trimethoprim-sulfamethoxazole as monotherapy - they lack reliable streptococcal coverage and must be combined with a beta-lactam 1, 2

• Do not overlook the distinction between cellulitis and purulent collections (abscesses, furuncles) - purulent collections require incision and drainage as primary treatment, with antibiotics playing only a subsidiary role 1, 2

• Blood cultures are not routinely recommended for typical cellulitis, but should be obtained for patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1, 2

Monitoring and Follow-Up

• Patients should show clinical improvement within 24-48 hours of starting appropriate antibiotics. 1

• Reassess at 5 days to determine if treatment extension is needed. 1, 2

• Consider outpatient treatment for patients without SIRS, altered mental status, or hemodynamic instability. 1