Antibiotic Treatment for Cellulitis of the Lower Leg

First-Line Antibiotic Selection

The American College of Physicians recommends first-line treatment with an antibiotic active against streptococci, such as penicillin, amoxicillin, dicloxacillin, cephalexin, or clindamycin, for 5 days if clinical improvement occurs 1, 2
For mild cellulitis, oral options include cephalexin 500 mg four times daily 4, dicloxacillin 500 mg four times daily 5, and clindamycin 300-450 mg four times daily for penicillin-allergic patients 1
For moderate to severe cellulitis, parenteral options include cefazolin 1 g every 8 hours IV 4, 6, nafcillin 1-2 g every 4-6 hours IV 4, and penicillin G 2-4 million units every 4-6 hours IV 4

5 days of antibiotic therapy is as effective as 10 days for uncomplicated cellulitis if clinical improvement occurs within the first 5 days 2, 7
Treatment should be extended if the infection has not improved within 5 days 4, 3

MRSA is an unusual cause of typical cellulitis, with β-lactam therapy successful in 96% of patients 1
Consider MRSA coverage when cellulitis is associated with penetrating trauma 4, 1, 6, evidence of MRSA infection elsewhere 4, nasal colonization with MRSA 4, history of injection drug use 4, 1, presence of purulent drainage 1, 3, or presence of systemic inflammatory response syndrome (SIRS) 4
Oral MRSA coverage options include clindamycin alone 1, trimethoprim-sulfamethoxazole 1, 3, and doxycycline 1
Intravenous MRSA coverage options include vancomycin 4, 1, linezolid 4, 1, daptomycin 1, and telavancin 1

Elevation of the affected area to promote gravity drainage of edema and inflammatory substances is recommended 4, 1
Treatment of predisposing factors such as edema, venous insufficiency, or underlying cutaneous disorders is recommended 4, 6
Careful examination of interdigital toe spaces in lower extremity cellulitis to identify and treat fissuring, scaling, or maceration is recommended 4, 6
Systemic corticosteroids could be considered in non-diabetic adult patients to hasten resolution 4, 6

Hospitalization is recommended for patients with concern for deeper or necrotizing infection 4, 6, poor adherence to therapy 4, 6, infection in a severely immunocompromised patient 4, 6, outpatient treatment failure 4, 6, or presence of SIRS, altered mental status, or hemodynamic instability 4, 6

Identification and treatment of predisposing conditions such as edema, obesity, eczema, venous insufficiency, and toe web abnormalities is recommended 4, 3
Prophylactic antibiotics may be considered for patients with 3-4 episodes per year despite addressing predisposing factors, including oral penicillin or erythromycin twice daily for 4-52 weeks 4 or intramuscular benzathine penicillin every 2-4 weeks 4