Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients
© The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com..
OBJECTIVES: We aimed to identify rational empirical dosing strategies for cefepime treatment in critically ill patients by utilizing population pharmacokinetics and target attainment analysis.
PATIENTS AND METHODS: 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.
RESULTS: 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.
CONCLUSIONS: 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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:78 |
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| Enthalten in: |
The Journal of antimicrobial chemotherapy - 78(2023), 6 vom: 01. Juni, Seite 1460-1470 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
An, Guohua [VerfasserIn] |
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| Links: |
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| Themen: |
807PW4VQE3 |
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| Anmerkungen: |
Date Completed 02.06.2023 Date Revised 19.04.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1093/jac/dkad106 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM35575486X |
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| 100 | 1 | |a An, Guohua |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Population pharmacokinetics and target attainment analyses to identify a rational empirical dosing strategy for cefepime in critically ill patients |
| 264 | 1 | |c 2023 | |
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| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © The Author(s) 2023. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please e-mail: journals.permissionsoup.com. | ||
| 520 | |a OBJECTIVES: We aimed to identify rational empirical dosing strategies for cefepime treatment in critically ill patients by utilizing population pharmacokinetics and target attainment analysis | ||
| 520 | |a PATIENTS AND METHODS: 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 | ||
| 520 | |a RESULTS: 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 | ||
| 520 | |a CONCLUSIONS: 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
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| 650 | 7 | |a 807PW4VQE3 |2 NLM | |
| 650 | 7 | |a Anti-Bacterial Agents |2 NLM | |
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| 700 | 1 | |a Wu, Nan |e verfasserin |4 aut | |
| 700 | 1 | |a Nation, Roger L |e verfasserin |4 aut | |
| 700 | 1 | |a Gu, Kenan |e verfasserin |4 aut | |
| 700 | 1 | |a Nalbant, Demet |e verfasserin |4 aut | |
| 700 | 1 | |a Jimenez-Truque, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a Fissell, William |e verfasserin |4 aut | |
| 700 | 1 | |a Patel, Pratish C |e verfasserin |4 aut | |
| 700 | 1 | |a Fishbane, Nicholas |e verfasserin |4 aut | |
| 700 | 1 | |a Watanabe, Amy |e verfasserin |4 aut | |
| 700 | 1 | |a Rolsma, Stephanie |e verfasserin |4 aut | |
| 700 | 1 | |a Kirkpatrick, Carl M J |e verfasserin |4 aut | |
| 700 | 1 | |a Landersdorfer, Cornelia B |e verfasserin |4 aut | |
| 700 | 1 | |a Winokur, Patricia |e verfasserin |4 aut | |
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