Pharmacokinetics and pharmacodynamics of oral cephalexin in children with osteoarticular infections.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Autmizguine, J; Watt, KM; Théorêt, Y; Kassir, N; Laferrière, C; Parent, S; Tapiéro, B; Ovetchkine, P

Published Date

  • December 2013

Published In

Volume / Issue

  • 32 / 12

Start / End Page

  • 1340 - 1344

PubMed ID

  • 23811740

Pubmed Central ID

  • 23811740

Electronic International Standard Serial Number (EISSN)

  • 1532-0987

Digital Object Identifier (DOI)

  • 10.1097/INF.0b013e3182a222a6

Language

  • eng

Conference Location

  • United States