Population Pharmacokinetics and Safety of Piperacillin-Tazobactam Extended Infusions in Infants and Children.
Antimicrob Agents Chemother
; 63(11)2019 11.
Article
em En
| MEDLINE
| ID: mdl-31427292
ABSTRACT
Piperacillin-tazobactam (TZP) is frequently used to treat severe hospital-acquired infections in children. We performed a single-center, pharmacokinetic (PK) trial of TZP in children ranging in age from 2 months to 6 years from various clinical subpopulations. Children who were on TZP per the standard of care were prospectively included and assigned to receive a dose of 80 mg/kg of body weight every 6 h infused over 2 h (ages 2 to 5 months) or a dose of 90 mg/kg every 8 h infused over 4 h (ages 6 months to 6 years). Separate population PK models were developed for piperacillin and tazobactam using nonlinear mixed-effects modeling. Optimal dosing was judged based on the ability to maintain free piperacillin concentrations above the piperacillin MIC for enterobacteria and Pseudomonas aeruginosa for ≥50% of the dosing interval. Any untoward event occurring during treatment was collected as an adverse event. A total of 79 children contributed 174 PK samples. The median (range) age and weight were 1.7 years (2 months to 6 years) and 11.4 kg (3.8 to 27.6 kg), respectively. A 2-compartment model with first-order elimination best described the piperacillin and tazobactam data. Both final population PK models included weight and concomitant furosemide administration on clearance and weight on the volume of distribution of the central compartment. The optimal dosing regimens in children with normal renal function, based on the piperacillin component, were 75 mg/kg/dose every 4 h infused over 0.5 h in infants ages 2 to ≤6 months and 130 mg/kg/dose every 8 h infused over 4 h in children ages >6 months to 6 years against bacteria with MICs up to 16 mg/liter. A total of 44 children (49%) had ≥1 adverse event, with 3 of these (site infiltrations) considered definitely associated with the extended infusions.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Piperacilina
/
Combinação Piperacilina e Tazobactam
/
Tazobactam
Tipo de estudo:
Observational_studies
/
Risk_factors_studies
Limite:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Antimicrob Agents Chemother
Ano de publicação:
2019
Tipo de documento:
Article