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Cefuroxime pharmacokinetics and pharmacodynamics for intravenous dosage regimens with 750 mg or 1500 mg doses in healthy young volunteers

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@article{4adcbf128f734586bd3e70fe713b7021,
title = "Cefuroxime pharmacokinetics and pharmacodynamics for intravenous dosage regimens with 750 mg or 1500 mg doses in healthy young volunteers",
abstract = "Introduction. Cefuroxime is an important antibiotic to treat several serious infections. Rapid elimination through the kidneys and the variation in MICs of various susceptible pathogens such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae give rise to dosing issues, especially in otherwise healthy patients. Aim. To investigate the probability of target attainment (PTA) for obtaining the optimal dosage regimens for cefuroxime in healthy young people. Methodology. Two weeks apart 750 and 1500 mg cefuroxime were administered as an intravenous bolus to 20 healthy volunteers (mean age: 27 years). Population modelling and simulation studies were done based on the obtained data for cefuroxime plasma concentration. Results. With a target value of time above MIC (T >MIC) greater than 50% the simulations revealed that a PTA of >99% is obtained for S. pneumoniae with a dosage regimen of 750 mg q12h. For E. coli and K. pneumoniae the PTA was <90% even with the highest, simulated dosage of 1500 mg q6h. For S. aureus a dosage of 1500 mg q8h gave a PTA above 97%. Conclusions. S. pneumoniae is most likely treatable with a two-daily dose of 750 mg cefuroxime. Not treatable are K. pneumoniae and E. coli. For S. aureus 1500 mg q8h constitutes an optimal dosing schedule. ",
keywords = "Breakpoints, Cefuroxime, Healthy volunteers, Pharmacodynamics, Pharmacokinetics, Population modelling, Anti-Bacterial Agents/administration & dosage, Humans, Middle Aged, Klebsiella pneumoniae/drug effects, Male, Healthy Volunteers, Escherichia coli/drug effects, Staphylococcus/drug effects, Cefuroxime/administration & dosage, Staphylococcal Infections/drug therapy, Klebsiella Infections/drug therapy, Microbial Sensitivity Tests, Young Adult, Escherichia coli Infections/drug therapy, Streptococcus pneumoniae/drug effects, Adult, Female, Monte Carlo Method",
author = "Sara Th{\o}nnings and Jensen, {Klaus S} and Nielsen, {Ninna B} and Martin Skj{\o}nnemand and Hansen, {Dennis S} and Lange, {Kai H W} and Niels Frimodt-M{\o}ller",
year = "2020",
month = mar,
doi = "10.1099/jmm.0.001138",
language = "English",
volume = "69",
pages = "387--395",
journal = "Journal of Medical Microbiology",
issn = "0022-2615",
publisher = "Society for General Microbiology",
number = "3",

}

RIS

TY - JOUR

T1 - Cefuroxime pharmacokinetics and pharmacodynamics for intravenous dosage regimens with 750 mg or 1500 mg doses in healthy young volunteers

AU - Thønnings, Sara

AU - Jensen, Klaus S

AU - Nielsen, Ninna B

AU - Skjønnemand, Martin

AU - Hansen, Dennis S

AU - Lange, Kai H W

AU - Frimodt-Møller, Niels

PY - 2020/3

Y1 - 2020/3

N2 - Introduction. Cefuroxime is an important antibiotic to treat several serious infections. Rapid elimination through the kidneys and the variation in MICs of various susceptible pathogens such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae give rise to dosing issues, especially in otherwise healthy patients. Aim. To investigate the probability of target attainment (PTA) for obtaining the optimal dosage regimens for cefuroxime in healthy young people. Methodology. Two weeks apart 750 and 1500 mg cefuroxime were administered as an intravenous bolus to 20 healthy volunteers (mean age: 27 years). Population modelling and simulation studies were done based on the obtained data for cefuroxime plasma concentration. Results. With a target value of time above MIC (T >MIC) greater than 50% the simulations revealed that a PTA of >99% is obtained for S. pneumoniae with a dosage regimen of 750 mg q12h. For E. coli and K. pneumoniae the PTA was <90% even with the highest, simulated dosage of 1500 mg q6h. For S. aureus a dosage of 1500 mg q8h gave a PTA above 97%. Conclusions. S. pneumoniae is most likely treatable with a two-daily dose of 750 mg cefuroxime. Not treatable are K. pneumoniae and E. coli. For S. aureus 1500 mg q8h constitutes an optimal dosing schedule.

AB - Introduction. Cefuroxime is an important antibiotic to treat several serious infections. Rapid elimination through the kidneys and the variation in MICs of various susceptible pathogens such as Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae give rise to dosing issues, especially in otherwise healthy patients. Aim. To investigate the probability of target attainment (PTA) for obtaining the optimal dosage regimens for cefuroxime in healthy young people. Methodology. Two weeks apart 750 and 1500 mg cefuroxime were administered as an intravenous bolus to 20 healthy volunteers (mean age: 27 years). Population modelling and simulation studies were done based on the obtained data for cefuroxime plasma concentration. Results. With a target value of time above MIC (T >MIC) greater than 50% the simulations revealed that a PTA of >99% is obtained for S. pneumoniae with a dosage regimen of 750 mg q12h. For E. coli and K. pneumoniae the PTA was <90% even with the highest, simulated dosage of 1500 mg q6h. For S. aureus a dosage of 1500 mg q8h gave a PTA above 97%. Conclusions. S. pneumoniae is most likely treatable with a two-daily dose of 750 mg cefuroxime. Not treatable are K. pneumoniae and E. coli. For S. aureus 1500 mg q8h constitutes an optimal dosing schedule.

KW - Breakpoints

KW - Cefuroxime

KW - Healthy volunteers

KW - Pharmacodynamics

KW - Pharmacokinetics

KW - Population modelling

KW - Anti-Bacterial Agents/administration & dosage

KW - Humans

KW - Middle Aged

KW - Klebsiella pneumoniae/drug effects

KW - Male

KW - Healthy Volunteers

KW - Escherichia coli/drug effects

KW - Staphylococcus/drug effects

KW - Cefuroxime/administration & dosage

KW - Staphylococcal Infections/drug therapy

KW - Klebsiella Infections/drug therapy

KW - Microbial Sensitivity Tests

KW - Young Adult

KW - Escherichia coli Infections/drug therapy

KW - Streptococcus pneumoniae/drug effects

KW - Adult

KW - Female

KW - Monte Carlo Method

UR - http://www.scopus.com/inward/record.url?scp=85082634929&partnerID=8YFLogxK

U2 - 10.1099/jmm.0.001138

DO - 10.1099/jmm.0.001138

M3 - Journal article

C2 - 31958049

VL - 69

SP - 387

EP - 395

JO - Journal of Medical Microbiology

JF - Journal of Medical Microbiology

SN - 0022-2615

IS - 3

ER -

ID: 59662451