Journal article
Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients
Journal of antimicrobial chemotherapy, Vol.78(6), pp.1460-1470
06/2023
DOI: 10.1093/jac/dkad106
PMCID: PMC10474939
PMID: 37071586
Abstract
We aimed to identify rational empirical dosing strategies for cefepime treatment in critically ill patients by utilizing population pharmacokinetics and target attainment analysis.
A prospective and opportunistic pharmacokinetic (PK) study was conducted in 130 critically ill patients in two ICU sites. The plasma concentrations of cefepime were determined using a validated LC-MS/MS method. All cefepime PK data were analysed simultaneously using the non-linear mixed-effects modelling approach. Monte Carlo simulations were performed to evaluate the PTA of cefepime at different MIC values following different dose regimens in subjects with different renal functions.
The PK of cefepime in critically ill patients was best characterized by a two-compartment model with zero-order input and first-order elimination. Creatinine clearance and body weight were identified to be significant covariates. Our simulation results showed that prolonged 3 h infusion does not provide significant improvement on target attainment compared with the traditional intermittent 0.5 h infusion. In contrast, for a given daily dose continuous infusion provided much higher breakpoint coverage than either 0.5 h or 3 h intermittent infusions. To balance the target attainment and potential neurotoxicity, cefepime 3 g/day continuous infusion appears to be a better dosing regimen than 6 g/day continuous infusion.
Continuous infusion may represent a promising strategy for cefepime treatment in critically ill patients. With the availability of institution- and/or unit-specific cefepime susceptibility patterns as well as individual patients' renal function, our PTA results may represent useful references for physicians to make dosing decisions.
Details
- Title: Subtitle
- Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients
- Creators
- Guohua An - University of IowaC Buddy Creech - Vanderbilt University Medical CenterNan Wu - University of IowaRoger L Nation - Monash UniversityKenan Gu - National Institute of Allergy and Infectious DiseasesDemet Nalbant - University of IowaNatalia Jimenez-Truque - Vanderbilt University Medical CenterWilliam Fissell - Vanderbilt University Medical CenterPratish C Patel - Vanderbilt University Medical CenterNicholas Fishbane - EmmesAmy Watanabe - EmmesStephanie Rolsma - Vanderbilt University Medical CenterCarl M J Kirkpatrick - Monash UniversityCornelia B Landersdorfer - Monash UniversityPatricia Winokur - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Journal of antimicrobial chemotherapy, Vol.78(6), pp.1460-1470
- DOI
- 10.1093/jac/dkad106
- PMID
- 37071586
- PMCID
- PMC10474939
- eISSN
- 1460-2091
- Grant note
- DOI: 10.13039/100015691, name: Division of Microbiology and Infectious Diseases, National Institutes of Allergy and Infectious Diseases; DOI: 10.13039/100000002, name: National Institutes of Health; name: Vaccine and Treatment Evaluation Unit, award: HHSN272200800008C
- Language
- English
- Electronic publication date
- 04/18/2023
- Date published
- 06/2023
- Academic Unit
- Infectious Diseases; Pharmaceutical Sciences and Experimental Therapeutics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984398208302771
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