Continuous infusion of piperacillin-tazobactam significantly improves target attainment in children with cancer and fever.
continuous infusion
dose optimization
febrile neutropenia
pharmacokinetics
piperacillin
target attainment
Journal
Cancer reports (Hoboken, N.J.)
ISSN: 2573-8348
Titre abrégé: Cancer Rep (Hoboken)
Pays: United States
ID NLM: 101747728
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
02
09
2021
received:
30
06
2021
accepted:
25
10
2021
pubmed:
20
11
2021
medline:
19
10
2022
entrez:
19
11
2021
Statut:
ppublish
Résumé
Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β-lactam concentrations. This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin-tazobactam, in order to optimize the dosing regimen. This prospective PK study included children with cancer, aged 1-17 years, who were treated with piperacillin-tazobactam for suspected or verified infection. A piperacillin-tazobactam loading dose (100 mg/kg) was administered followed by continuous infusion (300 mg/kg/day). The unbound fraction of piperacillin was quantified by high-performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100% fT > MIC) and 50% fT > 4xMIC. We included 68 fever episodes among 38 children with a median (IQR) age of 6.5 years and body weight of 27.4 kg (15.1-54.0). A three-compartment model adequately described the concentration-time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2 L/h/70 kg (13.0; 15.3) and 47.6 mg/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the P. aeruginosa breakpoint (16 mg/L) with the target of 100% fT > MIC, and a daily dose of 300 mg/kg reached optimal PTA. The strict target of 50% fT > 4xMIC (64 mg/L) was not feasibly attained by any dosing regimen at recommended doses. Unlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100% fT > MIC to be reached for children with febrile neutropenia.
Sections du résumé
BACKGROUND
Children with febrile neutropenia commonly exhibit alterations of pharmacokinetic (PK) parameters, leading to decreased β-lactam concentrations.
AIMS
This study evaluated piperacillin PK and probability of target attainment (PTA) with continuous infusion of piperacillin-tazobactam, in order to optimize the dosing regimen.
METHODS
This prospective PK study included children with cancer, aged 1-17 years, who were treated with piperacillin-tazobactam for suspected or verified infection. A piperacillin-tazobactam loading dose (100 mg/kg) was administered followed by continuous infusion (300 mg/kg/day). The unbound fraction of piperacillin was quantified by high-performance liquid chromatography and PK were described using population PK modeling. PK data was used to update and extend a previous PK model built on data following intermittent administration. Monte Carlo simulations were performed to assess PTA for targets of 100% time above the minimum inhibitory concentration (100% fT > MIC) and 50% fT > 4xMIC.
RESULTS
We included 68 fever episodes among 38 children with a median (IQR) age of 6.5 years and body weight of 27.4 kg (15.1-54.0). A three-compartment model adequately described the concentration-time data. Median (95% confidence interval) estimates for clearance and piperacillin concentration at steady state were 14.2 L/h/70 kg (13.0; 15.3) and 47.6 mg/L (17.2; 129.5), respectively. Body weight or lean body weight was significantly associated with the PK parameters, and body weight was integrated in the final PK model. Based on piperacillin exposure, continuous infusion was the only dosing regimen to achieve optimal PTA for the P. aeruginosa breakpoint (16 mg/L) with the target of 100% fT > MIC, and a daily dose of 300 mg/kg reached optimal PTA. The strict target of 50% fT > 4xMIC (64 mg/L) was not feasibly attained by any dosing regimen at recommended doses.
CONCLUSION
Unlike conventional piperacillin intermittent administration and extended infusion regimens, continuous infusion allows the target of 100% fT > MIC to be reached for children with febrile neutropenia.
Identifiants
pubmed: 34796702
doi: 10.1002/cnr2.1585
pmc: PMC9575485
doi:
Substances chimiques
Anti-Bacterial Agents
0
Piperacillin, Tazobactam Drug Combination
157044-21-8
Piperacillin
X00B0D5O0E
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e1585Informations de copyright
© 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.
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