Recommended Dosage of Cephalexin (Keflex) for Uncomplicated Cellulitis

For uncomplicated cellulitis, the recommended dosage of cephalexin (Keflex) is 500 mg orally four times daily for 5-7 days. 1, 2

Rationale for Cephalexin Selection

Cellulitis is primarily caused by streptococci, particularly group A streptococcus, with Staphylococcus aureus as a potential secondary pathogen 3
Cephalexin is a first-line oral antibiotic for typical cellulitis according to the Infectious Diseases Society of America (IDSA) guidelines 1
Other appropriate first-line options include penicillin, amoxicillin, amoxicillin-clavulanate, dicloxacillin, or clindamycin 1

For adults with uncomplicated cellulitis, the FDA-approved dosage is 500 mg orally every 6 hours (four times daily) 2
The total daily adult dosage range for cephalexin is 1-4 g divided into multiple doses 2
For pediatric patients, the recommended dosage is 25-50 mg/kg/day divided into four doses 2

For uncomplicated cellulitis, a 5-day course of antimicrobial therapy is as effective as a 10-day course if clinical improvement has occurred by day 5 1
The 2019 National Institute for Health and Care Excellence (NICE) guideline recommends a course of 5-7 days 1
The DANCE (Duration of Antibiotic Therapy for Cellulitis) trial compared 6-day versus 12-day courses and found similar rates of cure 1

MRSA is an unusual cause of typical cellulitis according to IDSA guidelines 1
Coverage for MRSA may be prudent in specific situations:
- Cellulitis associated with penetrating trauma 1
- Presence of purulent drainage 1
- Concurrent evidence of MRSA infection elsewhere 1
- History of intravenous drug use 1
If MRSA coverage is necessary, options include:
- Clindamycin 300-450 mg orally three times daily 1
- Trimethoprim-sulfamethoxazole (TMP-SMX) 1-2 double-strength tablets twice daily 1
- Doxycycline 100 mg orally twice daily 1

A 2023 pilot randomized controlled trial compared high-dose (1000 mg) to standard-dose (500 mg) cephalexin four times daily for 7 days 4
Preliminary results showed treatment failure in 12.9% of standard-dose patients versus 3.2% in the high-dose group, though with more minor adverse events in the high-dose group 4
A 2017 randomized clinical trial found that adding TMP-SMX to cephalexin did not significantly improve clinical cure rates compared to cephalexin alone in the per-protocol analysis 5

Elevation of the affected area to promote gravity drainage of edema and inflammatory substances 1
Treatment of any predisposing conditions such as tinea pedis, trauma, or venous eczema 1, 3
Consider systemic corticosteroids in nondiabetic adult patients with cellulitis to hasten resolution 1

Concomitant acid suppressive therapy may reduce cephalexin efficacy, with one study showing a 40% failure rate for cephalexin versus 20% for comparator antibiotics 6
Ensure adequate dosing and duration - underdosing may lead to treatment failure 4
Monitor for clinical improvement within 48-72 hours; consider alternative antibiotics if no improvement 1
Be vigilant for signs of necrotizing fasciitis, which requires immediate surgical intervention 1