Background: Osteoarticular infections lead to significant morbidity in children. Cephalexin has in vitro activity against methicillin-susceptible Staphylococcus aureus, a predominant pathogen in osteoarticular infection. However, cephalexin pharmacokinetics (PK) and pharmacodynamics (PD) are poorly described in children. This study described cephalexin PK in children treated for osteoarticular infection and assessed the proportion of children achieving surrogate PK/PD target for efficacy in methicillin-susceptible S. aureus infection.
Methods: Children with osteoarticular infection, 1 to 18 years of age, were eligible for this study if they were receiving oral cephalexin per standard of care. PK plasma samples were collected at specified times after multiple doses. PK parameters were estimated using noncompartmental analysis. PK/PD target for efficacy was calculated using the child’s PK parameters, minimum inhibitory concentration (MIC) of the isolate when available and previously described MIC of 2 and 4 mg/L.
Results: Twelve children were enrolled and PK profiles were obtained from 11 of them. Median age was 7 years, and median cephalexin dose was 40 mg/kg/dose every 8 hours. Median apparent oral clearance, apparent oral volume of distribution and elimination half-life (T1/2) were 0.29 L/h/kg, 0.44 L/kg and 1.1 h, respectively. Time above MIC (T>MIC) was greater than 40% of the dosing interval in 100%, 90% and 80% of the children when MICs were 0.25, 2 and 4 mg/L, respectively.
Conclusions: Oral cephalexin achieved optimal plasma exposure and was well tolerated in children with osteoarticular infection. Correlation between osteoarticular infection clinical outcome and PK/PD parameters needs further evaluation.
From the *Department of Pediatrics, Sainte-Justine University Hospital Center, Montreal, QC; †Duke Clinical Research Institute, Duke University Medical Center, Durham, NC; ‡Clinical Pharmacology Unit, Sainte-Justine University Hospital Center; §Pharsight a Certara Company; ¶Department of Microbiology; and ‖Department of Surgery, Sainte-Justine University Hospital Center, Montreal, QC.
Accepted for publication June 25, 2013.
J.A. receives support from Training Award, Fonds Irma-Levasseur, Pediatric Department, Sainte-Justine University Hospital Center. K.M.W. receives support from the Pediatric Trials Network (Government Contract HHSN275201000002I), NIGMS (1T32GM086330-01A1) and the Thrasher Research Fund for his work in pediatric clinical pharmacology. This work was supported by the research center of Sainte-Justine University Hospital. The authors have no other funding or conflicts of interest to disclose.
Address for correspondence: Philippe Ovetchkine, MD, Sainte-Justine University Hospital Center, 3175 Côte Sainte-Catherine, Montreal (QC) H3T 1C5, Canada. E-mail: firstname.lastname@example.org.