What are the guidelines for managing cellulitis?

Cellulitis Management Guidelines

First-Line Antibiotic Therapy

Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, with a 96% success rate, confirming that MRSA coverage is routinely unnecessary. 1

Recommended Oral Agents

• Cephalexin 500 mg every 6 hours is the preferred first-line agent 1, 2
• Dicloxacillin 250-500 mg every 6 hours 1, 3
• Amoxicillin or penicillin V 250-500 mg four times daily 1, 3
• Amoxicillin-clavulanate 875/125 mg twice daily 1, 2
• Clindamycin 300-450 mg every 6 hours (covers both streptococci and MRSA) 1, 2

Intravenous Options for Hospitalized Patients

• Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam 1, 2
• Nafcillin or oxacillin 2 g IV every 6 hours 1

Treatment Duration

Treat for exactly 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe. 1, 3 Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1. Five-day courses are as effective as 10-day courses based on high-quality randomized controlled trial evidence 1, 3.

When to Add MRSA Coverage

MRSA is an uncommon cause of typical cellulitis even in high-prevalence settings, and routine coverage is unnecessary. 1, 4 Add MRSA-active antibiotics ONLY when specific risk factors are present 1, 3:

MRSA Risk Factors

• Penetrating trauma or injection drug use 1, 3, 4
• Purulent drainage or exudate 1, 3
• Evidence of MRSA infection elsewhere or known nasal colonization 1, 3
• Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90, hypotension 1, 3
• Failure to respond to beta-lactam therapy after 48-72 hours 1, 2

MRSA Coverage Options

Outpatient oral regimens:

• Clindamycin 300-450 mg every 6 hours (monotherapy—covers both streptococci and MRSA) 1, 2
• Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 DS tablets twice daily PLUS a beta-lactam 1, 3
• Doxycycline 100 mg twice daily PLUS a beta-lactam 1, 3

Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis—their activity against beta-hemolytic streptococci is unreliable. 1, 3

Inpatient IV regimens:

• Vancomycin 15-20 mg/kg IV every 8-12 hours (first-line, A-I evidence) 1, 2
• Linezolid 600 mg IV twice daily 1, 3
• Daptomycin 4 mg/kg IV once daily 1, 3
• Clindamycin 600 mg IV every 8 hours (only if local MRSA resistance <10%) 1

Severe Cellulitis Requiring Broad-Spectrum Coverage

For patients with signs of systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required. 1, 2

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, 2
• 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
• Linezolid PLUS piperacillin-tazobactam 1

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

Hospitalization Criteria

Admit patients with any of the following 1, 2, 3:

• SIRS criteria (fever, tachycardia, hypotension, altered mental status) 1, 3
• Severe immunocompromise or neutropenia 1
• Concern for necrotizing infection or deeper infection 1, 2
• Failure of outpatient treatment after 24-48 hours 1, 2
• Hemodynamic instability 1

Essential Adjunctive Measures

Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances—this is crucial and often neglected. 1, 3

Additional Measures

• Examine interdigital toe spaces for tinea pedis, fissuring, scaling, or maceration—treating these eradicates colonization and reduces recurrence 1, 3
• Treat predisposing conditions: venous insufficiency, lymphedema, chronic edema, eczema, obesity 1, 3, 5
• Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in non-diabetic adults only—evidence is limited but may hasten resolution 1, 3, 6

Management 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 1, 3:

Prophylactic Antibiotic Options

• Oral penicillin V 250 mg-1 g twice daily 1, 3
• Oral erythromycin 250 mg twice daily 1, 3
• Intramuscular benzathine penicillin every 2-4 weeks 1, 3

Duration: 4-52 weeks based on recurrence pattern 1

Special Populations and Situations

Diabetic Patients

• Require longer treatment duration than non-diabetic patients 2
• Avoid systemic corticosteroids in diabetic patients despite evidence of benefit in non-diabetics 2
• Consider broader coverage with amoxicillin-clavulanate or second/third-generation cephalosporins for diabetic foot infections 1

Penicillin Allergy

• Clindamycin 300-450 mg every 6 hours (99.5% of S. pyogenes strains remain susceptible) 2, 3
• Levofloxacin 500 mg daily (reserve for beta-lactam allergies) 1
• For cephalosporin allergy: penicillins with dissimilar side chains or carbapenems can be safely used 1

Bite-Associated Cellulitis

• Amoxicillin-clavulanate 875/125 mg twice daily as monotherapy provides single-agent coverage for polymicrobial oral flora 1, 2
• Do NOT add TMP-SMX to this regimen 1

Treatment Failure Algorithm

Reassess within 24-48 hours for outpatients to ensure clinical improvement. 2 If no improvement with appropriate first-line antibiotics 1, 2:

Step 1: Assess Severity Markers

• Temperature >38°C, heart rate >90, respiratory rate >24 2
• WBC >12,000 or <4,000 2
• Presence of purulent drainage 2
• Systemic toxicity or hemodynamic instability 2

Step 2: Add Empiric MRSA Coverage

For outpatients with rising WBC or worsening infection:

• Add TMP-SMX 1-2 DS tablets twice daily PLUS continue beta-lactam 2
• OR switch to clindamycin 300-450 mg three times daily 2
• OR add doxycycline 100 mg twice daily PLUS continue beta-lactam 2

For hospitalized patients with treatment failure:

• Start vancomycin 15-20 mg/kg IV every 8-12 hours 2
• Obtain blood cultures 2
• Consider wound culture if any drainage present 2

Step 3: Consider Alternative Diagnoses

• Abscess requiring incision and drainage 2
• Deep vein thrombosis mimicking cellulitis 2
• Necrotizing fasciitis (severe pain out of proportion, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1, 2

Do not delay switching therapy—waiting beyond 48-72 hours of failed therapy increases morbidity. 2

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, 3
• Do not use doxycycline or TMP-SMX as monotherapy—inadequate streptococcal coverage 1, 3
• Do not extend treatment beyond 5 days automatically—only extend if clinical improvement has not occurred 1, 2, 3
• Do not use systemic corticosteroids in diabetic patients 2
• Blood cultures are positive in only 5% of cases and are unnecessary for typical cellulitis 2, 4
• Cutaneous inflammation may worsen initially after starting antibiotics due to sudden bacterial destruction releasing inflammatory enzymes—this is expected 3