Piperacillin Population Pharmacokinetics and Dosing Regimen Optimization in Critically Ill Children Receiving Continuous Renal Replacement Therapy.
Michael ThySaïk UrienFrantz FoissacNaïm BouazzaInès GanaEmmanuelle BilleAgathe BérangerJulie ToubianaRomain BerthaudFabrice LesageSylvain RenolleauJean-Marc TréluyerSihem BenaboudMehdi OualhaPublished in: Antimicrobial agents and chemotherapy (2022)
We aimed to develop a piperacillin population pharmacokinetic (PK) model in critically ill children receiving continuous renal replacement therapy (CRRT) and to optimize dosing regimens. The piperacillin plasma concentration was quantified by high-performance liquid chromatography. Piperacillin PK was investigated using a nonlinear mixed-effect modeling approach. Monte Carlo simulations were performed to compute the optimal scheme of administration according to the target of 100% interdose interval time in which concentration is one to four times above the MIC (100% fT > 1 to 4× MIC). A total of 32 children with a median (interquartile range [IQR]) postnatal age of 2 years (0 to 11), body weight (BW) of 15 kg (6 to 38), and receiving CRRT were included. Concentration-time courses were best described by a one-compartment model with first-order elimination. BW and residual diuresis ( Q u ) explained some between-subject variabilities on volume of distribution ( V ), where [Formula: see text], and clearance (CL), where [Formula: see text], where CL pop and V pop are 6.78 L/h and 55.0 L, respectively, normalized to a 70-kg subject and median residual diuresis of 0.06 mL/kg/h. Simulations with intermittent and continuous administrations for 4 typical patients with different rates of residual diuresis (0, 0.1, 0.25, and 0.5 mL/kg/h) showed that continuous infusions were appropriate to attain the PK target for patients with residual diuresis higher than 0.1 mL/kg/h according to BW and MIC, while for anuric patients, less frequent intermittent doses were mandatory to avoid accumulation. Optimal exposure to piperacillin in critically ill children on CRRT should be achieved by using continuous infusions with escalating doses for high-MIC bacteria, except for anuric patients who require less frequent intermittent doses.
Keyphrases
- young adults
- monte carlo
- high performance liquid chromatography
- body weight
- acute kidney injury
- end stage renal disease
- high intensity
- chronic kidney disease
- mass spectrometry
- molecular dynamics
- newly diagnosed
- preterm infants
- smoking cessation
- tandem mass spectrometry
- peritoneal dialysis
- high resolution
- atomic force microscopy
- single molecule
- liquid chromatography
- finite element
- visible light