792. A Pharmacokinetic Validation Study of Once Daily Dosing of Intravenous Gentamicin and Tobramycin in Paediatric Patients
Session: Poster Abstract Session: Antimicrobial Agents: PK/PD Studies
Friday, October 9, 2015
Room: Poster Hall
  • Erin Chung - Poster 792.pdf (561.8 kB)
  • Background: Aminoglycosides are commonly used for treating serious infections caused by gram-negative organisms.  Despite evidence to support once daily dosing in the adult population, there is limited experience in children. We aimed to evaluate the ability of a daily dose of 9 mg/kg of intravenous gentamicin and tobramycin to achieve target maximum concentration (Cmax) range of 16-25 mg/L in paediatric patients in our institution.

    Methods: This retrospective observational cohort study assessed children receiving gentamicin or tobramycin.  Pharmacokinetic parameters were calculated using serum levels drawn 3 hours and 6 hours after a dose of aminoglycoside. Descriptive statistics and Monte Carlo simulations were used in our analysis.

    Results: One hundred and forty seven children with 153 aminoglycoside courses aged 2 months to 18 years were included. Majority of patients were admitted to surgical units (63.4%).  Seventy one percent of aminoglycoside courses were indicated for empiric use, 24% for microbiologically-documented infections, and 5% for prophylaxis.  Mean population pharmacokinetic parameters were: volume of distribution of 0.51±0.28 L/kg, clearance of 2.83±1.33 mL/min/kg and half-life of 2.13±0.65 h.  With first dose of therapy, 44.3% of all courses reached target therapeutic Cmax range.  The mean Cmax of gentamicin and tobramycin was 18.65±7.78 mg/L.  Monte Carlo simulations demonstrated a minimal increase in proportion of simulated patients achieving target Cmax range with a dose increase from 9 mg/kg to 10 mg/kg (33.5% vs. 33.7%, respectively). Ninety-three percent of patients defervesced by end of treatment course. The median change from baseline for: white blood cell count was -16.46% (interquartile range (IQR): -37.32 to 9.41), serum creatinine was 5.84% (IQR: -10.96 to 19.18), blood urea nitrogen was 2.27% (IQR: -28.57 to 73.03), and urine output was -13.37% (IQR: -42.02 to 24.51). One patient had audiometry testing, which was normal.

    Conclusion: An initial gentamicin or tobramycin daily dose of 9 mg/kg is appropriate to achieve target Cmax range and appears to be efficacious and safe for paediatric patients.  Monitoring serum aminoglycoside concentrations remains an important strategy to optimize dose for efficacy and safety.

    Erin Chung, HonBSc, BScPhm, RPh1,2, Rachel Xia-Ying Liu, PharmD candidate2, Marina Strzelecki, BScPhm, ACPR, RPh1,2, Michael Pe, BScPhm, ACPR, RPh1,2, Laura Wang, BScPhm, ACPR, RPh1,2, Vicky Papaioannou, MClSc, AUD(C), Reg. CASPLO1, Elizabeth Harvey, MD, FRCPC1, Susan Richardson, MD, FRCPC1, Ari Bitnun, MD, MSc, FRCPC1 and Winnie Seto, BScPhm, PharmD, MSc, ACPR, RPh1,2, (1)The Hospital for Sick Children, Toronto, ON, Canada, (2)Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada


    E. Chung, None

    R. X. Y. Liu, None

    M. Strzelecki, None

    M. Pe, None

    L. Wang, None

    V. Papaioannou, None

    E. Harvey, None

    S. Richardson, None

    A. Bitnun, None

    W. Seto, None

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