903. Pharmacokinetics of amikacin in children with cancer and febrile neutropenia
Session: Poster Abstract Session: Antimicrobial Utilization and Resistance in Children
Saturday, October 22, 2011
Room: Poster Hall B1
  • AkIDSA2011.pdf (888.6 kB)
  • Background: The pharmacokinetic of amikacin in children with cancer can be affected by the differences in volume of distribution (Vd) and clearance (Cl) status during a febrile neutropenia (FN) episode resulting in an adverse outcome or therapeutic failure. The aim of this study was to compare the amikacin PK/PD parameters in monodose versus multiple doses in children with FN

    Methods: Prospective study. Children with cancer and FN in a paediatric Chilean hospital were enrolled after parental informed consent was signed. The patients randomly received intravenous amikacin: group A: (7.5 mg/kg every 12 h) and group B: (15 mg/kg/day every 24 h).  We used plasmatics baseline levels measures (C basal) and peaks (Cpeak) with polarized fluorescense immuneassay technique TDxFLx (Abbot Lab). The Bayesian model was calculate after the amikacin steady state was reached. The pharmacokinetic parameters were analyzed with NONMEM IV software.

    Results: We studied 30 FN episodes; 12 in group A and 18 in group B. The observed Vd was higher than expected in both groups (23.50 L and 15.24 L vs 10.58 L) at hour 24 (P 0.01). The observed half-life time in group A was 2.94 h - 3.48 h at 24 and 48 hours respectively; and 7.6 h - 7.36 h at 24 and 48 hours respectively in group B (expected 1.5 h, P 0.01). Amikacin Cl at 24 h presented a 37.89% increase in group A and 23.46% decrease in group B (P 0.0121). C max level in therapeutic range defined as > 30 mg/ml was reached in 1 subject of group A and in 6/18 subjects in group B, with an average at 24 h of 16.47 mg/ml in group A and 24.27 mg/ml in group B. Both groups maintained adequate baseline amikacin levels, defined as < 2 mg/ml.

    Conclusion: the amikacin PK/PD parameters in children with cancer and FN were altered increasing the risk of therapeutic failure. The Vd and half-life time were higher than expected. Amikacin Cl was decreased in monodose group. A monodose administration and tailored strategy could be recommended in children with cancer during a FN episode

    Subject Category: P. Pediatric and perinatal infections

    Rodolfo Villena, MD1, Marcela Rabello2, Jorge Morales2, Rodrigo Aravena2, Katherine Kopp2, Milena Villarroel, MD3,4 and Marķa Elena Santolaya, MD3, (1)University of Chile, Santiago, Chile, (2)Calvo Mackenna children hospital, Santiago, Chile, (3)Universidad de Chile, Santiago, Chile, (4)Oncology Unit, Hospital Luis Calvo Mackenna, Santiago, Chile


    R. Villena, None

    M. Rabello, None

    J. Morales, None

    R. Aravena, None

    K. Kopp, None

    M. Villarroel, None

    M. E. Santolaya, None

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