Treatment of Cellulitis
First-Line Antibiotic Selection
For typical nonpurulent cellulitis, beta-lactam monotherapy is the standard of care and is successful in 96% of patients, making MRSA coverage unnecessary in most cases. 1, 2
Oral Regimens for Uncomplicated Cellulitis
- Cephalexin 500 mg orally four times daily is the preferred first-line agent for mild cellulitis without systemic signs 1
- Alternative beta-lactams include penicillin, amoxicillin, amoxicillin-clavulanate, or dicloxacillin 250-500 mg every 6 hours 1, 2
- Clindamycin 300-450 mg orally four times daily is appropriate for penicillin-allergic patients, providing coverage for both streptococci and MRSA 1, 2
Intravenous Regimens for Hospitalized Patients
- Cefazolin 1-2 g IV every 8 hours is the preferred IV beta-lactam for uncomplicated cellulitis requiring hospitalization 2
- Oxacillin 2 g IV every 6 hours is an alternative 2
- These regimens remain appropriate even in the inpatient setting if the cellulitis is nonpurulent and lacks MRSA risk factors 2
Treatment Duration
Treat for 5 days if clinical improvement occurs; 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
- Patients should demonstrate clinical improvement within 24-48 hours of starting appropriate antibiotics 1
- Mandatory reassessment at 48 hours is critical, as treatment failure rates of 21% have been reported with some regimens 2
When to Add MRSA Coverage
MRSA coverage should be added only when specific risk factors are present 1, 2:
High-Risk Scenarios Requiring MRSA Coverage
- Penetrating trauma or injection drug use 1, 2
- Purulent drainage or exudate 1, 2
- Evidence of MRSA infection elsewhere or nasal MRSA colonization 1
- Systemic inflammatory response syndrome (SIRS) 1, 2
- Failure to respond to beta-lactam therapy after 48 hours 2
MRSA-Active Regimens
Oral options:
- Clindamycin 300-450 mg orally four times daily (monotherapy covering both streptococci and MRSA) 1, 2
- Trimethoprim-sulfamethoxazole (SMX-TMP) plus a beta-lactam (combination required, as SMX-TMP lacks reliable streptococcal activity) 1, 2
- Doxycycline 100 mg orally twice daily plus a beta-lactam (combination required, as doxycycline lacks reliable streptococcal activity) 1, 2
IV options for hospitalized patients:
- Vancomycin 15-20 mg/kg IV every 8-12 hours is first-line for complicated cellulitis (A-I evidence) 2
- Linezolid 600 mg IV twice daily (equally effective alternative, A-I evidence) 2
- Daptomycin 4 mg/kg IV once daily (A-I evidence) 2
- Clindamycin 600 mg IV three times daily (only if local MRSA resistance <10%, A-III evidence) 2
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 Broad-Spectrum Therapy
- Fever, hypotension, tachycardia, or altered mental status 1, 2
- Severe pain out of proportion to examination 2
- Skin anesthesia, rapid progression, gas in tissue, or bullous changes 2
- Suspected necrotizing fasciitis or polymicrobial infection 1, 2
Recommended 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
- Linezolid 600 mg IV twice daily PLUS piperacillin-tazobactam 2
- Vancomycin PLUS a carbapenem (meropenem 1 g IV every 8 hours) 2
- Vancomycin PLUS ceftriaxone 2 g IV daily and metronidazole 500 mg IV every 8 hours 2
- Penicillin plus clindamycin is specifically recommended for documented group A streptococcal necrotizing fasciitis 2
Critical Action Steps
- Obtain emergent surgical consultation if necrotizing infection is suspected 2
- Treatment duration for severe infections is 7-14 days, guided by clinical response 2
- Blood cultures should be obtained for patients with malignancy, severe systemic features, neutropenia, or severe immunodeficiency 1, 2
Adjunctive Measures
Elevation of the affected extremity hastens improvement by promoting gravity drainage of edema and inflammatory substances. 1, 2
Additional Supportive Care
- Treat predisposing conditions including tinea pedis, venous eczema, trauma, and chronic edema 1, 2
- Carefully examine interdigital toe spaces for fissuring, scaling, or maceration that may harbor pathogens 1, 2
- Systemic corticosteroids (prednisone 40 mg daily for 7 days) could be considered in non-diabetic adults to reduce inflammation, though evidence is limited (weak recommendation, moderate evidence) 1, 2, 3
Indications for Hospitalization
Hospitalize patients with any of the following 1, 2:
- Systemic inflammatory response syndrome (SIRS): fever >38°C, tachycardia >90 bpm, tachypnea >24 rpm 2
- Hypotension, hemodynamic instability, or altered mental status 1, 2
- Severe immunocompromise or neutropenia 2
- Concern for deeper or necrotizing infection 1, 2
- Poor adherence to therapy or failure of outpatient treatment 1
Common Pitfalls to Avoid
Do Not Reflexively Add MRSA Coverage
- MRSA is an uncommon cause of typical cellulitis, even in hospitals with high MRSA prevalence 2
- Adding MRSA coverage without specific risk factors represents overtreatment and increases antibiotic resistance 2
- Beta-lactam monotherapy succeeds in 96% of typical cellulitis cases 1, 2, 4
Do Not Use Doxycycline or SMX-TMP as Monotherapy
- These agents lack reliable activity against beta-hemolytic streptococci, the primary pathogen in cellulitis 1, 2
- Always combine with a beta-lactam when using these agents for cellulitis 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 2, 4
- Reassess for MRSA risk factors, necrotizing infection, or misdiagnosis 2
Distinguish Cellulitis from Purulent Collections
- Furuncles, abscesses, and septic bursitis require incision and drainage as primary treatment, not antibiotics alone 2
- Use point-of-care ultrasound if clinical uncertainty exists 2, 5
Prevention of Recurrence
Each attack of cellulitis causes lymphatic inflammation and possibly permanent damage, with severe or repeated episodes leading to lymphedema. 1
Preventive Measures
- Treat interdigital maceration and keep skin well hydrated with emollients 1
- Reduce underlying edema through elevation, compression stockings, or diuretic therapy if appropriate 1
- Address predisposing conditions including obesity, venous insufficiency, and toe web abnormalities 2
Prophylactic Antibiotics
For frequent infections despite preventive measures 1:
- Monthly intramuscular benzathine penicillin injections
- Oral therapy with twice-daily erythromycin or penicillin V