Cephalexin (Keflex) Can Be Started at 40 mg/kg/day in Infants as Young as 7 Days of Age
Based on the most recent pharmacokinetic evidence, cephalexin at doses of 25 mg/kg every 6-8 hours (totaling 75-100 mg/kg/day, which encompasses the 40 mg/kg/day range) can be safely initiated in infants as young as 7-60 days of age, with dosing adjustments based on post-natal and post-menstrual age. 1
Age-Specific Dosing Framework
Infants 7-60 Days Old
- Recent 2025 pharmacokinetic data demonstrates that cephalexin 25 mg/kg/dose every 6-8 hours achieves appropriate pharmacodynamic targets in infants as young as 7 days post-natal age. 1
- For Enterobacterales infections, 25 mg/kg every 6 hours (100 mg/kg/day) achieved >90% target attainment in this age group. 1
- For methicillin-susceptible Staphylococcus aureus (MSSA), 25 mg/kg every 8 hours (75 mg/kg/day) was sufficient. 1
- Maturational changes in gastrointestinal absorption and renal clearance require consideration of both post-natal age (affecting absorption) and post-menstrual age (affecting clearance). 1
Children >3 Months Old
- For MSSA pneumonia and serious infections, the preferred oral cephalexin dose is 75-100 mg/kg/day divided into 3-4 doses, which aligns with the 40 mg/kg/day minimum threshold. 2
- Standard dosing for most infections ranges from 25-100 mg/kg/day depending on severity. 2
Critical Age Considerations and Caveats
Neonates <7 Days
- The available evidence does not support cephalexin use in neonates younger than 7 days of age. 1
- The pharmacokinetic study specifically enrolled infants starting at 7 days post-natal age, leaving a data gap for the first week of life. 1
Practical Dosing Strategy
For a 40 mg/kg/day total daily dose:
- Infants 7-60 days: Use 10-13 mg/kg every 6-8 hours (depending on pathogen and severity), which totals approximately 40-52 mg/kg/day. 1
- Children >3 months: Use 10-13 mg/kg every 6-8 hours as part of the 25-100 mg/kg/day range for mild-to-moderate infections. 2
Higher Dose Requirements
- Recent 2025 data supports high-dose cephalexin (45 mg/kg/dose, maximum 1.5g) three times daily (135 mg/kg/day total) for bone and joint infections in children 1-18 years, demonstrating excellent efficacy and tolerability. 3
- This substantially exceeds 40 mg/kg/day and shows that higher doses are both safe and effective when clinically indicated. 3
Important Clinical Pitfalls
- Do not use cephalexin in neonates <7 days old without alternative evidence, as pharmacokinetic data is lacking for this population. 1
- Children have greater body water turnover and may require higher per-kilogram doses than adults to achieve therapeutic concentrations. 4
- Renal function must be considered: patients with creatinine clearance <30 mL/min require dose reduction proportional to decreased function. 4
- The 40 mg/kg/day dose represents the lower end of the therapeutic range; many infections require 75-100 mg/kg/day for optimal outcomes. 2