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Piperacillin pharmacokinetics and target attainment in children with cancer and fever: Can we optimize our dosing strategy?
Maarbjerg, Sabine F; Thorsted, Anders; Kristoffersson, Anders; Friberg, Lena E; Nielsen, Elisabet I; Wang, Mikala; Brock, Birgitte; Schrøder, Henrik.
Afiliação
  • Maarbjerg SF; Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
  • Thorsted A; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Kristoffersson A; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Friberg LE; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Nielsen EI; Department of Pharmaceutical Biosciences, Uppsala University, Uppsala, Sweden.
  • Wang M; Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark.
  • Brock B; Steno Diabetes Centre, Copenhagen, Gentofte, Denmark.
  • Schrøder H; Department of Pediatrics and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark.
Pediatr Blood Cancer ; 66(6): e27654, 2019 06.
Article em En | MEDLINE | ID: mdl-30740885
ABSTRACT

BACKGROUND:

Data on piperacillin-tazobactam pharmacokinetics and optimal dosing in children with cancer and fever are limited. Our objective was to investigate piperacillin pharmacokinetics and the probability of target attainment (PTA) with standard intermittent administration (IA), and to simulate PTA in other dosing regimens. PROCEDURE This prospective pharmacokinetic study was conducted from April 2016 to January 2018. Children with cancer receiving empiric piperacillin-tazobactam to treat infections were included. Piperacillin-tazobactam 100 mg/kg was infused over 5 min every 8 hours (IA). An optimized sample schedule provided six blood samples per subject for piperacillin concentration determination. The evaluated targets included (1) 100% time of free piperacillin concentration above the minimum inhibitory concentration (fT > MIC) and (2) 50% fT > 4× MIC. MIC50 and MIC90 were defined based on an intrainstitutional MIC range.

RESULTS:

A total of 482 piperacillin concentrations were obtained from 43 children (aged 1-18 years) during 89 fever episodes. Standard IA resulted in insufficient target attainment, with significant differences in piperacillin pharmacokinetics for different body weights. Median fT > MIC was 61.2%, 53.5%, and 36.3% for MIC50 (2.0 mg/L), MIC90 (4.0 mg/L), and breakpoint for Pseudomonas aeruginosa (16.0 mg/L), respectively. Correspondingly, the median fT > 4× MIC was 43%, 36.3%, and 20.1%. Simulations showed that only continuous infusion reached a PTA of 95% for MIC = 16.0 mg/L, while extended infusion lasting half of the dosing interval reached a PTA of 95% for MIC ≤ 8 mg/L.

CONCLUSIONS:

Our data revealed insufficient PTA with standard IA of piperacillin-tazobactam in children with cancer and fever. Alternative dosing strategies, preferably continuous infusion, are required to ensure adequate PTA.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperacilina / Febre / Antibacterianos / Neoplasias Tipo de estudo: Etiology_studies / Health_economic_evaluation / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Piperacilina / Febre / Antibacterianos / Neoplasias Tipo de estudo: Etiology_studies / Health_economic_evaluation / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adolescent / Child / Child, preschool / Female / Humans / Infant / Male Idioma: En Ano de publicação: 2019 Tipo de documento: Article