• J. Antimicrob. Chemother. · Mar 2017

    Clinical Trial

    Population pharmacokinetics of cefazolin before, during and after cardiopulmonary bypass to optimize dosing regimens for children undergoing cardiac surgery.

    • Pieter A J G De Cock, Hussain Mulla, Sarah Desmet, Filip De Somer, Brett C McWhinney, Jacobus P J Ungerer, Annelies Moerman, Sabrina Commeyne, Vande Walle Johan J Department of Paediatric Nephrology, Ghent University Hospital, Ghent, Belgium., Katrien Francois, Johan G C Van Hasselt, and Peter De Paepe.
    • Department of Pharmacy, Ghent University Hospital, Ghent, Belgium.
    • J. Antimicrob. Chemother. 2017 Mar 1; 72 (3): 791-800.

    ObjectivesThe 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 And MethodsThis 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.ResultsA 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.ConclusionsWe propose an optimized dosing regimen for cefazolin during cardiac surgery in paediatric patients to avoid treatment failure due to inadequate antibiotic prophylaxis.© The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…