881. Pharmacokinetics and Pharmacodynamics of Oral Cephalexin in Children with Osteo-articular Infection
Session: Poster Abstract Session: Bone, Joint, and Soft Tissue Infection
Friday, October 19, 2012
Room: SDCC Poster Hall F-H
Posters
  • poster 881 PK_PD Cephalexin.pdf (358.8 kB)
  • Background:

    Cephalexin (CPX) is effective against oxacillin-susceptible Staphylococcus aureus, the main pathogen in osteo-articular infections (OAI). Its efficacy correlates with Pharmacokinetic/Pharmacodynamic (PK/PD) parameters: the time that concentration is above the Minimum Inhibitory Concentration (MIC) (T>MIC) for the pathogen. However, CPX PK is not well documented in children and oral therapy for OAI is controversial.

    We aimed to describe CPX PK in children treated for OAI, in order to assess the proportion of children achieving a PK/PD target of efficacy for S. aureus infection: T>MIC> 40%.

    Methods:

    We conducted a CPX PK study (Jan 2010-Jan 2012) at steady-state, in children 1 to18 years of age treated for OAI. PK sampling was collected immediately before and 60, 90, 120 and 360 minutes after drug administration. Plasma concentrations were measured using a validated High-performance liquid chromatography method. PK parameters were estimated using a one-compartment model (WinNonlin®, Pharsight).

    T>MIC for the 8h dosing interval was calculated using i) Patient PK parameters; ii) MIC of the isolate when available, and an extrapolated MIC of 2 and 4 µg/mL.

    Results:

    PK profiles were obtained from 10 children with median age of 7 years (range: 2-18). Mean CPX dosage was 130 mg/kg/day (Standard deviation (SD): 15) divided in 3 doses (max 4.5 g/day). Mean half-life of elimination, apparent volume of distribution and clearance were 1.2 h (SD: 0.7), 0.35 L/kg (SD: 0.15) and 4.4 ml/min/kg (SD: 1.5), respectively. Mean area under the concentration-time curve (AUC0-8h) was 9783 min*µg/mL (SD: 3160).

    A bacterial pathogen was isolated in 6 subjects, and all strains were S. aureus with a CPX MIC below 0.25 µg/mL.

    T>MIC for 8h dosing interval are summarized in the table 1.

    Table 1: PK/PD parameters

    MIC (μg/mL)

    0.25

    2

    4

    T > MIC (%)

    - Mean (SD)

    - Median (Range)

     

    138 (96)

    121 (50-396)

     

    92 (69)

    80 (34-280)

      

    77 (60)

    64 (28-242)

    All children achieved a T>MIC greater than 40% of the dosing interval using an MIC of 0.25 µg/mL. For MIC of 2 and 4 µg/mL, 90% of children achieved a T>MIC above 40%.

    Conclusion:

    All children receiving CPX achieved PK/PD targets predicting CPX efficacy in susceptible staphylococcal infection. These results support the use of oral CPX in children for OAI therapy.

    Julie Autmizguine, MD1, Yves Théorêt, PhD2, Nastya Kassir3,4, Céline Laferrière, MD5, Stefan Parent, MD, PhD6, Bruce Tapiero, MD7 and Philippe Ovetchkine, MD, MSc7, (1)Pediatric Infectious Division, Sainte-Justine Hospital, Montreal, QC, Canada, (2)CHU Sainte-Justine - Université de Montréal, Montréal, QC, Canada, (3)Clinical Pharmacology Unit, Sainte-Justine Hospital, Montreal, QC, Canada, (4)Pharsight a Certara Company, Montreal, QC, Canada, (5)CHU Sainte-Justine, Montréal, QC, Canada, (6)Surgery, Sainte-Justine Hospital, Montreal, QC, Canada, (7)Department of Pediatrics, Division of Infectious Diseases, CHU Sainte-Justine – University of Montreal, Montreal, QC, Canada

    Disclosures:

    J. Autmizguine, None

    Y. Théorêt, None

    N. Kassir, None

    C. Laferrière, None

    S. Parent, None

    B. Tapiero, None

    P. Ovetchkine, None

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