Keflex (Cephalexin) Dosing for Skin Infections
For adults with skin infections, prescribe cephalexin 500 mg orally four times daily (every 6 hours) for 7-10 days, but only after confirming the absence of MRSA risk factors, as cephalexin is completely ineffective against MRSA. 1, 2
Critical Pre-Treatment Assessment: MRSA Risk Stratification
Before prescribing cephalexin, you must rule out MRSA risk factors, as this is the most common pitfall in treating skin infections 1, 2:
Cephalexin is appropriate ONLY when:
- Non-purulent cellulitis without systemic signs of infection 1, 2
- Confirmed methicillin-susceptible Staphylococcus aureus (MSSA) or streptococcal infection 1, 2
- No MRSA risk factors present 1, 2
Do NOT use cephalexin when any of these are present:
- Purulent drainage 1, 2
- Systemic signs of infection (SIRS criteria) 1, 2
- History of MRSA colonization or previous MRSA infection 1, 2
- Injection drug use 1, 2
- Failed initial antibiotic therapy 1, 2
- Penetrating trauma 2
For MRSA-risk scenarios, use instead: trimethoprim-sulfamethoxazole, doxycycline, clindamycin, or vancomycin 3, 1, 2
Standard Adult Dosing Regimen
Primary recommendation: 500 mg orally four times daily (every 6 hours) for 7-10 days 3, 1, 2, 4
Alternative dosing: For uncomplicated skin infections, 500 mg every 12 hours may be used, though the four-times-daily regimen provides more consistent coverage 4, 5
Maximum daily dose: Do not exceed 4 grams per day 1, 2, 4
The IDSA guidelines specifically recommend the 500 mg four times daily regimen for optimal coverage of MSSA and streptococcal skin infections 1. The FDA label supports both dosing schedules, but clinical studies demonstrate equivalent efficacy with either 250 mg four times daily or 500 mg twice daily 4, 5.
Pediatric Dosing
Standard dose: 25-50 mg/kg/day divided into 4 doses 3, 6, 4
Alternative for skin infections: Total daily dose may be divided and administered every 12 hours for children over 1 year of age 4
Severe infections: Dosage may be doubled 4
Treatment duration is typically 7-10 days depending on clinical response 6.
Treatment Duration and Monitoring
Duration: 7-10 days depending on clinical response 1, 2, 6
Critical monitoring timepoint: Clinical improvement should be evident within 48-72 hours of initiating therapy 1, 2, 6
If no improvement at 72 hours, consider:
- Alternative diagnoses 1, 2, 6
- Resistant organisms, particularly MRSA 1, 2
- Deeper or necrotizing infection 1, 2
The IDSA recommends extending treatment beyond 5 days if infection has not improved, and completing the full course even if symptoms resolve early 1, 2.
Special Populations
Penicillin-allergic patients: Cephalexin is suitable for those without immediate hypersensitivity reactions 3, 1, 2, 6
Pregnant patients: FDA pregnancy category B; generally considered safe 1, 2, 6
Renal impairment: Patients with creatinine clearance less than 30 mL/min require dose reduction proportional to reduced renal function 7
Specific Infection Types
Impetigo: 250 mg four times daily for adults; 25 mg/kg/day in 4 divided doses for children 3
MSSA skin and soft tissue infections: 500 mg four times daily for adults; 25 mg/kg/day in 4 divided doses for children 3
Critical Contraindications and Red Flags
Necrotizing fasciitis: Requires immediate broad-spectrum IV antibiotics and urgent surgical debridement; cephalexin should never be used 1, 2
Severely immunocompromised patients: Require broad-spectrum coverage rather than cephalexin alone (malignancy on chemotherapy, neutropenia, severe immunodeficiency, immersion injuries, animal bites) 2
Adjunctive Measures to Reduce Recurrence
- Elevate the affected extremity 1, 2
- Address predisposing factors: edema, obesity, eczema, venous insufficiency 2
- Examine interdigital toe spaces for tinea pedis or maceration in lower-extremity cellulitis 1, 2
Microbiologic Coverage
Cephalexin provides excellent coverage against MSSA and Streptococcus species, with 85-96% of isolates susceptible in clinical studies 6, 8. It is completely ineffective against MRSA 1, 2, 6. Clinical cure rates of 90-96% have been demonstrated in comparative trials for appropriate skin infections 5, 8, 9, 10.