Antibiotic Treatment for Cellulitis
First-Line Antibiotic Selection
For typical nonpurulent cellulitis, prescribe an oral antibiotic active against streptococci (penicillin, amoxicillin, cephalexin, dicloxacillin, or clindamycin) for 5 days. 1
Standard Nonpurulent Cellulitis
Oral options for streptococcal coverage include: 1
- Penicillin
- Amoxicillin
- Cephalexin (500 mg four times daily) 2
- Dicloxacillin
- Amoxicillin-clavulanate
- Clindamycin
These agents target β-hemolytic streptococci, which are the predominant pathogens in typical cellulitis 1, 3
MRSA is an unusual cause of typical cellulitis and routine coverage is unnecessary 1
Cellulitis Requiring MRSA Coverage
Add MRSA-active antibiotics only if specific risk factors are present: 1
- Penetrating trauma or injection drug use
- Purulent drainage present
- Evidence of MRSA infection elsewhere or nasal colonization
- Systemic inflammatory response syndrome (SIRS)
Oral MRSA-active options include: 1
- Trimethoprim-sulfamethoxazole (TMP-SMX) 1, 4
- Doxycycline or minocycline 1
- Clindamycin (covers both streptococci and MRSA) 1, 4
- Linezolid 600 mg twice daily 1
For dual streptococcal and MRSA coverage: 1
- Clindamycin alone, OR
- TMP-SMX or doxycycline PLUS a β-lactam (amoxicillin or cephalexin)
Note that TMP-SMX combined with cephalexin was no more effective than cephalexin alone for pure cellulitis without purulent features 1
Treatment Duration
The recommended duration is 5 days if clinical improvement has occurred by day 5. 1
Extension Criteria
- Extend treatment beyond 5 days only if the infection has not improved 1, 5
- Look for reduction in erythema, warmth, tenderness, swelling, and resolution of fever 5
- Continue the same antibiotic if it was appropriate for the suspected pathogen 5
- Total duration should be guided by clinical response, typically not exceeding 10-14 days 1, 3
A 5-day course is as effective as 10 days when clinical improvement occurs by day 5 1, 6. The IDSA guideline provides strong evidence (high quality) supporting this shorter duration 1
Hospitalized Patients with Complicated Cellulitis
For severe cellulitis requiring hospitalization, use IV antibiotics with MRSA coverage: 1
- Vancomycin 1 g IV every 12 hours 1
- Linezolid 600 mg IV/PO every 12 hours 1, 7
- Daptomycin 4 mg/kg IV once daily 1
- Telavancin 10 mg/kg IV once daily 1
Duration for complicated infections: 7-14 days 1
Adjunctive Measures
Address predisposing factors to prevent recurrence: 1, 5
- Elevate the affected extremity 1
- Examine interdigital toe spaces for fissuring, scaling, or maceration 1, 5
- Treat underlying conditions: edema, obesity, eczema, venous insufficiency, toe web abnormalities 1, 5
Consider systemic corticosteroids (prednisone 40 mg daily for 7 days) in nondiabetic adults 1
When to Hospitalize
Admit patients with: 1
- SIRS, altered mental status, or hemodynamic instability
- Concern for deeper or necrotizing infection
- Failure of outpatient treatment 5
- Severe immunocompromise 5
- Poor adherence anticipated
Common Pitfalls
- Do not routinely obtain cultures for typical cellulitis without systemic signs 1
- Reserve blood cultures for patients with malignancy, neutropenia, severe immunodeficiency, immersion injuries, or animal bites 1
- Avoid empiric MRSA coverage in typical nonpurulent cellulitis without risk factors, as β-lactams succeed in 96% of cases 1
- Do not use rifampin as monotherapy or adjunctive therapy for cellulitis 1