Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass to optimize dosing regimens for children undergoing cardiac surgery.
J Antimicrob Chemother
; 72(3): 791-800, 2017 03 01.
Article
in En
| MEDLINE
| ID: mdl-27999040
ABSTRACT
Objectives:
The objective of this study was to characterize cefazolin serum pharmacokinetics in children before, during and after cardiopulmonary bypass (CPB), in order to derive an evidence-based dosing regimen. Patients andmethods:
This study included children who received cefazolin before surgical incision, before cessation of CPB and after surgery. Blood samples of total and unbound cefazolin concentrations were collected before, during and after CPB. The cefazolin concentration-time profiles were analysed using population pharmacokinetic modelling and predictors for interindividual variability in pharmacokinetic parameters were investigated. Subsequently, optimized dosing regimens were developed using stochastic simulations. Clinicaltrials.gov NCT02749981.Results:
A total of 494 total and unbound cefazolin concentrations obtained from 56 children (aged 6 days to 15 years) were included. A two-compartment model with first-order elimination plus an additional compartment for the effect of CPB best described the data. Clearance (1.56 L/h), central volume (1.93 L) and peripheral volume (2.39 L) were allometrically scaled by body weight. The estimated glomerular filtration rate (eGFR) was identified as a covariate on clearance and the serum albumin concentration was associated with maximum protein binding capacity. Our simulations showed that an additional bolus dose at the start of CPB improves the PTA in typical patients from 59% to >94%. Prolonged surgery and preserved renal function (i.e. drop in eGFR <25%) had a negative impact on PTA.Conclusions:
We propose an optimized dosing regimen for cefazolin during cardiac surgery in paediatric patients to avoid treatment failure due to inadequate antibiotic prophylaxis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Cardiopulmonary Bypass
/
Cefazolin
/
Antibiotic Prophylaxis
/
Anti-Bacterial Agents
Type of study:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limits:
Adolescent
/
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
/
Newborn
Language:
En
Journal:
J Antimicrob Chemother
Year:
2017
Type:
Article
Affiliation country:
Belgium