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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...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2023
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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. |
format | Online Article Text |
id | pubmed-10511078 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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