Cephalexin Dosing for Skin Infections
For uncomplicated skin and soft tissue infections caused by methicillin-susceptible Staphylococcus aureus (MSSA) or Streptococcus, cephalexin should be dosed at 500 mg four times daily (QID) in adults or 25-50 mg/kg/day divided into 3-4 doses in children. 1, 2
Adult Dosing
The standard adult dose for skin and soft tissue infections is:
- 500 mg orally four times daily (QID) for typical infections 1, 2
- Alternative: 500 mg every 12 hours is FDA-approved for skin infections and may improve adherence 2
- Total daily dose range: 1-4 grams divided throughout the day 2
- Duration: Typically 7-10 days depending on clinical response 1
The twice-daily regimen (500 mg BID) is equally effective as four-times-daily dosing and offers the advantage of improved compliance, as demonstrated in multiple clinical trials showing >97% efficacy for both regimens. 3, 4
Pediatric Dosing
For children with skin infections:
- Standard dose: 25-50 mg/kg/day divided into 3-4 doses 1, 2
- Alternative: Total daily dose divided every 12 hours for streptococcal pharyngitis and skin infections in children >1 year 2
- Severe infections: Double the standard dose 2
Practical Pediatric Dosing (using suspension):
For four times daily dosing:
- 10 kg child: 1/2 to 1 tsp of 125 mg/5 mL suspension QID
- 20 kg child: 1 to 2 tsp of 125 mg/5 mL suspension QID
- 40 kg child: 2 to 4 tsp of 125 mg/5 mL suspension QID 2
Recent pharmacokinetic modeling suggests that twice-daily dosing at 22-45 mg/kg and three-times-daily dosing at 15-25 mg/kg achieve adequate drug levels for MSSA with MIC ≤2 mg/L, though these regimens require prospective validation. 5
Renal Impairment Adjustments
Dose reduction is required when creatinine clearance falls below 30 mL/min 6:
- The reduction should be proportional to decreased renal function
- Monitor serum creatinine or calculate creatinine clearance
- Since 70-100% of cephalexin is renally excreted unchanged within 6-8 hours, accumulation occurs with impaired clearance 6
Common pitfall: Failing to adjust doses in elderly patients or those with borderline renal function—always assess renal function before prescribing, especially in older adults where age-related decline may not be reflected in serum creatinine alone.
Clinical Context and Pathogen Coverage
Cephalexin is appropriate for:
- Impetigo (Staphylococcus and Streptococcus) 1
- Non-purulent cellulitis (when MSSA suspected) 1
- Uncomplicated skin and soft tissue infections 1
Critical limitation: Cephalexin is inactive against MRSA 1. If MRSA is suspected (purulent infections, prior MRSA history, high local prevalence, treatment failure), alternative agents like trimethoprim-sulfamethoxazole, doxycycline, or clindamycin should be used instead 1.
Key Advantages
- Excellent oral absorption with rapid tissue distribution 6
- Low protein binding and minimal metabolism 6
- Very low allergy incidence due to chemical stability 6
- Does not disturb lower bowel flora (absorbed high in intestinal tract) 6
- Suspension formulation available for pediatric use, stable for 14 days when refrigerated 2
Important Caveats
- For penicillin-allergic patients, cephalexin is acceptable except in those with immediate hypersensitivity reactions (anaphylaxis, urticaria) 1
- The guideline notes cephalexin is "not used much in pediatrics" compared to other options, though it remains FDA-approved and effective 1
- Streptococcal infections require at least 10 days of therapy to prevent rheumatic fever 2
- More severe infections or less susceptible organisms may require higher doses or parenteral cephalosporins if >4 g/day needed 2