Recommended Dose of Keflex (Cephalexin) for Cellulitis
For adults with cellulitis, prescribe cephalexin 500 mg orally four times daily (every 6 hours) for 5 days, extending treatment only if the infection has not improved within this timeframe. 1, 2
Adult Dosing
The FDA-approved dosing for skin and soft tissue infections is 250 mg every 6 hours, but 500 mg every 6 hours is the standard dose used in clinical practice for cellulitis 2. The IDSA guidelines specifically list cephalexin 500 mg four times daily as the recommended oral agent for methicillin-susceptible staphylococcal skin infections 1.
Alternative Dosing Considerations
- 500 mg every 12 hours may be used for mild, uncomplicated skin infections 2, though this is less commonly recommended for cellulitis specifically
- High-dose regimen (1000 mg four times daily) showed fewer treatment failures (3.2% vs 12.9%) in a 2023 pilot trial, though with more minor adverse effects 3. This may be considered for more severe cases, but remains investigational
Pediatric Dosing
For children with cellulitis: 25-50 mg/kg/day divided into 4 doses (every 6 hours) 1, 2
- For severe infections, this dose may be doubled
- A recent 2025 study supports high-dose cefalexin 45 mg/kg (maximum 1.5 g) three times daily as effective and well-tolerated 4, though this was specifically for bone/joint infections
Treatment Duration
5 days is the recommended duration, but extend treatment if the infection has not improved within this period 1. The IDSA guidelines emphasize this 5-day minimum with extension as needed based on clinical response.
Key Clinical Considerations
When Cephalexin is Appropriate
Cephalexin targets streptococci and methicillin-susceptible Staphylococcus aureus (MSSA), which are the typical pathogens in non-purulent cellulitis 1. Use cephalexin for:
- Mild cellulitis without systemic signs (no fever, tachycardia, or SIRS criteria)
- No purulent drainage or abscess
- No risk factors for MRSA
When to Choose Alternative Antibiotics
Do NOT use cephalexin alone if the patient has 1:
- Penetrating trauma
- Evidence of MRSA infection elsewhere or nasal colonization
- Injection drug use
- Purulent drainage
- Systemic signs of infection (SIRS criteria: fever, tachycardia, tachypnea)
In these cases, add MRSA coverage with trimethoprim-sulfamethoxazole, doxycycline, or clindamycin, or switch to vancomycin for severe infections 1.
Evidence Quality Note
A 2017 randomized trial of 496 patients found that adding trimethoprim-sulfamethoxazole to cephalexin did NOT improve cure rates in the per-protocol analysis (83.5% vs 85.5%, p=0.50) 5. This supports using cephalexin alone for typical non-purulent cellulitis, though the modified intention-to-treat analysis showed some imprecision.
Common Pitfalls
- Don't underdose: The 250 mg four times daily dose is insufficient for most cellulitis cases; use 500 mg four times daily
- Don't forget to examine toe webs: Treating interdigital tinea pedis reduces recurrence risk 1
- Don't overlook abscess: Always perform ultrasound if there's any concern for underlying abscess, as this requires drainage, not just antibiotics 1
- Monitor for treatment failure: If no improvement by day 3-4, reassess for abscess, resistant organisms, or alternative diagnoses 1