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Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery

OBJECTIVE: There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend opti...

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Autores principales: Alli, Ahmad, Paruk, Fathima, Roger, Claire, Lipman, Jeffrey, Calleemalay, Daren, Wallis, Steven C., Scribante, Juan, Richards, Guy A., Roberts, Jason A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511078/
https://www.ncbi.nlm.nih.gov/pubmed/37729151
http://dx.doi.org/10.1371/journal.pone.0291425
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author Alli, Ahmad
Paruk, Fathima
Roger, Claire
Lipman, Jeffrey
Calleemalay, Daren
Wallis, Steven C.
Scribante, Juan
Richards, Guy A.
Roberts, Jason A.
author_facet Alli, Ahmad
Paruk, Fathima
Roger, Claire
Lipman, Jeffrey
Calleemalay, Daren
Wallis, Steven C.
Scribante, Juan
Richards, Guy A.
Roberts, Jason A.
author_sort Alli, Ahmad
collection PubMed
description OBJECTIVE: There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend optimised dosing regimens. METHODS: Patients undergoing CPB for elective cardiac valve replacement were included using convenience sampling. Intravenous cefazolin (2g) was administered pre-incision and re-dosed at 4 hours. Serial blood and urine samples were collected and analysed using validated chromatography. Population PK modelling and Monte-Carlo simulations were performed using Pmetrics(®) to determine the fractional target attainment (FTA) of achieving unbound concentrations exceeding pre-defined exposures against organisms known to cause surgical site infections for 100% of surgery (100% fT(>MIC)). RESULTS: From the 16 included patients, 195 total and 64 unbound concentrations of cefazolin were obtained. A three-compartment linear population PK model best described the data. We observed that cefazolin 2g 4-hourly was insufficient to achieve the FTA of 100% fT(>MIC) for Staphylococcus aureus and Escherichia coli at serum creatinine concentrations ≤ 50 μmol/L and for Staphylococcus epidermidis at any of our simulated doses and serum creatinine concentrations. A dose of cefazolin 3g 4-hourly demonstrated >93% FTA for S. aureus and E. coli. CONCLUSIONS: We found that cefazolin 2g 4-hourly was not able to maintain concentrations above the MIC for relevant pathogens in patients with low serum creatinine concentrations undergoing cardiac surgery with CPB. The simulations showed that optimised dosing is more likely with an increased dose and/or dosing frequency.
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spelling pubmed-105110782023-09-21 Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery Alli, Ahmad Paruk, Fathima Roger, Claire Lipman, Jeffrey Calleemalay, Daren Wallis, Steven C. Scribante, Juan Richards, Guy A. Roberts, Jason A. PLoS One Research Article OBJECTIVE: There is little prospective data to guide effective dosing for antibiotic prophylaxis during surgery requiring cardiopulmonary bypass (CPB). We aim to describe the effects of CPB on the population pharmacokinetics (PK) of total and unbound concentrations of cefazolin and to recommend optimised dosing regimens. METHODS: Patients undergoing CPB for elective cardiac valve replacement were included using convenience sampling. Intravenous cefazolin (2g) was administered pre-incision and re-dosed at 4 hours. Serial blood and urine samples were collected and analysed using validated chromatography. Population PK modelling and Monte-Carlo simulations were performed using Pmetrics(®) to determine the fractional target attainment (FTA) of achieving unbound concentrations exceeding pre-defined exposures against organisms known to cause surgical site infections for 100% of surgery (100% fT(>MIC)). RESULTS: From the 16 included patients, 195 total and 64 unbound concentrations of cefazolin were obtained. A three-compartment linear population PK model best described the data. We observed that cefazolin 2g 4-hourly was insufficient to achieve the FTA of 100% fT(>MIC) for Staphylococcus aureus and Escherichia coli at serum creatinine concentrations ≤ 50 μmol/L and for Staphylococcus epidermidis at any of our simulated doses and serum creatinine concentrations. A dose of cefazolin 3g 4-hourly demonstrated >93% FTA for S. aureus and E. coli. CONCLUSIONS: We found that cefazolin 2g 4-hourly was not able to maintain concentrations above the MIC for relevant pathogens in patients with low serum creatinine concentrations undergoing cardiac surgery with CPB. The simulations showed that optimised dosing is more likely with an increased dose and/or dosing frequency. Public Library of Science 2023-09-20 /pmc/articles/PMC10511078/ /pubmed/37729151 http://dx.doi.org/10.1371/journal.pone.0291425 Text en © 2023 Alli et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Alli, Ahmad
Paruk, Fathima
Roger, Claire
Lipman, Jeffrey
Calleemalay, Daren
Wallis, Steven C.
Scribante, Juan
Richards, Guy A.
Roberts, Jason A.
Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
title Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
title_full Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
title_fullStr Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
title_full_unstemmed Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
title_short Peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
title_sort peri-operative pharmacokinetics of cefazolin prophylaxis during valve replacement surgery
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511078/
https://www.ncbi.nlm.nih.gov/pubmed/37729151
http://dx.doi.org/10.1371/journal.pone.0291425
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