What is the treatment for cellulitis?

Treatment of Cellulitis

For typical uncomplicated cellulitis, beta-lactam monotherapy with agents like cephalexin 500 mg four times daily or dicloxacillin 250-500 mg every 6 hours for 5 days is the standard of care, achieving 96% success rates without requiring MRSA coverage. 1

First-Line Antibiotic Selection

Beta-lactam monotherapy is the cornerstone of treatment for typical nonpurulent cellulitis, as MRSA is an uncommon cause even in high-prevalence settings. 1 The Infectious Diseases Society of America provides A-I level evidence supporting this approach. 1

Recommended Oral Agents:

• Cephalexin 500 mg orally four times daily 1
• Dicloxacillin 250-500 mg every 6 hours 1
• Amoxicillin (appropriate dosing) 1
• Amoxicillin-clavulanate 875/125 mg twice daily (particularly for bite-associated cellulitis) 1, 2
• Penicillin V 250-500 mg four times daily 1
• Clindamycin 300-450 mg every 6 hours (covers both streptococci and MRSA) 1

For Hospitalized Patients Requiring IV Therapy:

• Cefazolin 1-2 g IV every 8 hours (preferred IV beta-lactam) 1
• Nafcillin 2 g IV every 6 hours 1
• 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 represents a major shift from traditional 7-14 day courses, with high-quality randomized controlled trial evidence demonstrating that 5-day courses are as effective as 10-day courses for uncomplicated cellulitis. 1

When to Add MRSA Coverage

MRSA coverage should NOT be added reflexively - it is only indicated when specific risk factors are present. 1 The evidence is clear that adding MRSA coverage to beta-lactam therapy provides no additional benefit in typical cases. 1

Specific Indications for MRSA Coverage:

• Penetrating trauma or injection drug use 1, 2
• Purulent drainage or exudate 1, 2
• Evidence of MRSA infection elsewhere or known nasal colonization 1, 2
• Systemic inflammatory response syndrome (SIRS) - fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 1, 2
• Failure to respond to beta-lactam therapy after 48-72 hours 1

MRSA-Active Regimens When Indicated:

For outpatients:

• Clindamycin 300-450 mg orally every 6 hours (monotherapy - covers both streptococci and MRSA, but only if local resistance <10%) 1
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 DS tablets twice daily PLUS a beta-lactam (cephalexin, amoxicillin, or penicillin) 1, 3
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1

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

For hospitalized patients:

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

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
• Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 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

Treatment duration for severe infections: 7-14 days guided by clinical response, not the standard 5 days. 1

Indications for Hospitalization

Admit patients with any of the following:

• SIRS criteria (fever, tachycardia, hypotension, altered mental status) 1
• Hemodynamic instability 1
• Severe immunocompromise or neutropenia 1
• Concern for deeper or necrotizing infection 1
• Failure of outpatient treatment after 24-48 hours 1
• Poor adherence to therapy anticipated 1

Essential Adjunctive Measures

These non-antibiotic interventions are critical and often neglected:

• 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, 2
• Examine interdigital toe spaces carefully for tinea pedis, fissuring, scaling, or maceration - treating these eradicates colonization and reduces recurrent infection risk 1, 2
• Treat predisposing conditions: venous insufficiency, lymphedema, chronic edema, eczema, obesity 1, 2
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults, though evidence is limited 1, 2

Critical caveat: Avoid systemic corticosteroids in diabetic patients despite potential benefit in non-diabetics. 1

Special Populations and Scenarios

Penicillin/Cephalosporin Allergy:

• Clindamycin 300-450 mg orally every 6 hours (covers both streptococci and MRSA) 1
• Levofloxacin 500 mg daily (reserve for beta-lactam allergies; lacks reliable MRSA coverage) 1
• Linezolid 600 mg orally twice daily (expensive, reserved for complicated cases) 1

Bite-Associated Cellulitis:

• Amoxicillin-clavulanate 875/125 mg twice daily provides single-agent coverage for polymicrobial oral flora 1, 2

Diabetic Patients:

• Require longer treatment duration than the standard 5-day course 1
• Avoid systemic corticosteroids 1
• Elevation is especially important to promote drainage 1

Pediatric Dosing:

• Vancomycin 15 mg/kg IV every 6 hours (first-line for hospitalized children) 1
• Clindamycin 10-13 mg/kg/dose IV every 6-8 hours (if stable, no bacteremia, local resistance <10%) 1
• Doxycycline 2 mg/kg/dose orally every 12 hours (only for children >8 years and <45 kg; never under 8 years due to tooth discoloration) 1

Management of Treatment Failure

If no improvement after 48-72 hours of appropriate first-line antibiotics, reassess immediately. 1

Differential Diagnosis to Consider:

• MRSA infection (add empiric MRSA coverage immediately) 1
• Abscess requiring drainage (ultrasound if clinical uncertainty) 1
• Deep vein thrombosis mimicking cellulitis 1
• Necrotizing fasciitis (emergent surgical consultation) 1
• Resistant organisms 4

Warning Signs of Necrotizing Fasciitis:

• Severe pain out of proportion to examination 1
• Skin anesthesia 1
• Rapid progression 1
• Gas in tissue 1
• Bullous changes 1

If necrotizing infection suspected: Obtain emergent surgical consultation for diagnostic and therapeutic debridement, and initiate broad-spectrum combination therapy immediately. 1

Prevention of Recurrent Cellulitis

Annual recurrence rates are 8-20% in patients with previous leg cellulitis. 1 Each attack causes lymphatic inflammation and possibly permanent damage, with severe or repeated episodes potentially leading to lymphedema. 2

Preventive Strategies:

• Treat interdigital maceration and tinea pedis 1, 2
• Keep skin well hydrated with emollients 2
• Reduce underlying edema through elevation, compression stockings, or diuretic therapy if appropriate 2
• Manage venous insufficiency and lymphedema 1, 2

Prophylactic Antibiotics:

For patients with 3-4 episodes per year despite treating predisposing factors:

• Oral penicillin V 250 mg twice daily for 4-52 weeks 1
• Oral erythromycin 250 mg twice daily 1
• Intramuscular benzathine penicillin every 2-4 weeks 1

Common Pitfalls to Avoid

• Do not routinely add MRSA coverage for typical cellulitis without specific risk factors 1
• Do not extend treatment beyond 5 days automatically - only extend if clinical improvement has not occurred 1
• Do not use doxycycline or TMP-SMX as monotherapy - they lack adequate streptococcal coverage 1
• Do not delay surgical consultation if any signs of necrotizing infection are present 1
• Do not obtain blood cultures routinely - they are positive in only 5% of cases and unnecessary for typical cellulitis 1
• Do not use antibiotics alone for abscesses - incision and drainage is the primary treatment 1, 5