Management of Cellulitis
First-Line Antibiotic Therapy
Beta-lactam monotherapy is the standard of care for typical uncomplicated cellulitis, achieving 96% success rates even in high-MRSA-prevalence settings, and MRSA coverage should NOT be added reflexively. 1
Recommended Oral Agents for Uncomplicated Cellulitis
- Cephalexin, dicloxacillin (250-500 mg every 6 hours), penicillin, amoxicillin, or amoxicillin-clavulanate are all appropriate first-line choices for nonpurulent cellulitis 1
- Clindamycin (300-450 mg three times daily) provides coverage for both streptococci and MRSA if local resistance is <10%, avoiding the need for combination therapy 1
- MRSA is an uncommon cause of typical cellulitis, and beta-hemolytic streptococci or methicillin-sensitive S. aureus account for the majority of culturable cases 1, 2
Treatment Duration
- Treat for 5 days if clinical improvement occurs; extend only if symptoms have not improved within this timeframe 1
- Traditional 7-14 day courses are no longer necessary for uncomplicated cases 1
When to Add MRSA Coverage
MRSA-active antibiotics should be added ONLY when specific risk factors are present—not simply because community-associated MRSA exists in your area. 1
Specific Indications for MRSA Coverage
- Penetrating trauma or injection drug use 1
- Purulent drainage or exudate 1
- Known MRSA colonization or documented MRSA infection elsewhere 1
- Failure to respond to beta-lactam therapy after 48 hours 1
- Systemic inflammatory response syndrome (SIRS) with fever, hypotension, or altered mental status 1
Recommended MRSA-Active Regimens
- Clindamycin monotherapy (if local resistance <10%) provides both streptococcal and MRSA coverage 1
- Trimethoprim-sulfamethoxazole (TMP-SMX) PLUS a beta-lactam (e.g., cephalexin) 1
- Doxycycline 100 mg twice daily PLUS a beta-lactam 1
- Never use doxycycline or TMP-SMX as monotherapy for typical cellulitis, as their activity against beta-hemolytic streptococci is unreliable 1
Inpatient Management and IV Antibiotics
When to Hospitalize
- Systemic toxicity (fever, hypotension, tachycardia, altered mental status) 1
- Severe immunocompromise or neutropenia 1
- Suspected necrotizing fasciitis (severe pain out of proportion to exam, skin anesthesia, rapid progression, gas in tissue, bullous changes) 1
- Inability to tolerate oral medications or lack of outpatient follow-up 1
IV Antibiotic Selection for Hospitalized Patients
For uncomplicated cellulitis requiring hospitalization (nonpurulent, no MRSA risk factors):
- Cefazolin 1-2 g IV every 8 hours or nafcillin remain appropriate even in the inpatient setting, with 96% success rates 1
For complicated cellulitis or when MRSA coverage is needed:
- Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line (A-I evidence) 1
- Linezolid 600 mg IV twice daily is equally effective (A-I evidence) 1
- Daptomycin 4 mg/kg IV once daily is an alternative (A-I evidence) 1
- Clindamycin 600 mg IV three times daily if local MRSA resistance <10% (A-III evidence) 1
Severe Infections Requiring Broad-Spectrum Coverage
For patients with systemic toxicity, rapid progression, or suspected necrotizing fasciitis, mandatory broad-spectrum combination therapy is required:
- Vancomycin or linezolid PLUS piperacillin-tazobactam (3.375-4.5 g IV every 6 hours) 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
- Obtain emergent surgical consultation if necrotizing infection is suspected, as these progress rapidly and require debridement 1
Transition to Oral Therapy
- Transition to oral antibiotics (cephalexin, dicloxacillin, or clindamycin) once clinical improvement is demonstrated, typically after a minimum of 4 days of IV treatment 1
- Reassess in 24-48 hours to verify clinical response, as treatment failure rates of 21% have been reported with some regimens 1
Adjunctive Measures
- Elevate the affected extremity to promote gravity drainage of edema and inflammatory substances 1
- Treat predisposing conditions including tinea pedis and toe web abnormalities, venous insufficiency, lymphedema, eczema, and obesity 1
- Systemic corticosteroids (prednisone 30-40 mg daily for 7 days) could be considered in non-diabetic adults, though evidence is limited 1
Common Pitfalls to Avoid
- Do not obtain blood cultures in typical uncomplicated cases; reserve for patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1
- Do not continue ineffective antibiotics beyond 48 hours—progression despite appropriate therapy indicates resistant organisms or a deeper/different infection 1
- Assess for abscess with ultrasound if there is any clinical uncertainty, as purulent collections require incision and drainage plus MRSA-active antibiotics, not antibiotics alone 1
- Do not delay surgical consultation if any signs of necrotizing infection are present (severe pain out of proportion, rapid progression, systemic toxicity) 1
Special Considerations
Facial Cellulitis
- Treat with oral beta-lactam monotherapy (penicillin, amoxicillin, cephalexin, or dicloxacillin) for 5 days, as streptococci are the predominant pathogens 3
- MRSA coverage is not routinely needed unless specific risk factors are present 3
Foot Cellulitis
- Treat for 5-7 days with beta-lactam monotherapy unless MRSA risk factors are present 1
- Add MRSA coverage (TMP-SMX or doxycycline plus a beta-lactam, or clindamycin alone) if penetrating trauma, purulent drainage, or injection drug use is present 1
Pediatric Patients
- Vancomycin 15 mg/kg IV every 6 hours is first-line for hospitalized children with complicated cellulitis 1
- Clindamycin 10-13 mg/kg/dose IV every 6-8 hours if stable, no bacteremia, and local resistance <10% 1
- Linezolid 600 mg IV twice daily for children >12 years, or 10 mg/kg/dose IV every 8 hours for children <12 years 1
- Never use doxycycline in children under 8 years due to tooth discoloration and bone growth effects 1