Twice- and Thrice-daily Cephalexin Dosing for Staphylococcus aureus Infections in Children

Abstract

Background: Cephalexin is used for the treatment of methicillin-susceptible Staphylococcus aureus (MSSA) infections in children. Although 4 times daily dosing is recommended, less frequent dosing regimens are often prescribed to improve treatment acceptability and adherence. We developed a population pharmacokinetic model of cephalexin in children to determine a twice-daily (BID) and thrice-daily (TID) cephalexin dosing regimen for MSSA infections. Methods: A population pharmacokinetic model was developed using a nonlinear mixed effects modeling approach. The dataset used was from a prospective open-label pharmacokinetic study of orally administered cephalexin in 12 children 1-16 years of age with bone and joint infections. Simulations were performed to determine a BID and TID dosing regimen so that ≥90% of children in this age group would achieve the pharmacodynamic target for MSSA (ie, time that the free drug concentration exceeds the minimum inhibitory concentration of the bacteria for at least 40% of the dosing interval). Results: The final model was 1 compartment with a transit compartment model to account for delay in oral absorption. For BID dosing, doses of 22-45 and 80 mg/kg were required for MSSA with minimum inhibitory concentrations of 1-2 and 4 mg/L, respectively. For TID dosing, the respective required doses were 15-25 and 45 mg/kg. Conclusions: Our study proposes a BID and TID cephalexin dosing regimen that can be prospectively evaluated. Through reducing the dose frequency of this widely prescribed antibiotic, we can reduce the medication burden for children and improve treatment compliance for MSSA infections.