Ceftriaxone dosing in patients admitted from the emergency department with sepsis.

Szczegóły
Abstrakt

Tytuł:: Ceftriaxone dosing in patients admitted from the emergency department with sepsis.
Autorzy:: Heffernan AJ; School of Medicine, Griffith University, Southport, Australia. .; Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, University of Queensland, Woolloongabba, Australia. .
Curran RA; Department of Pharmacy, Gold Coast University Hospital, Southport, Australia.
Denny KJ; Department of Intensive Care, Gold Coast University Hospital, Southport, Australia.
Sime FB; Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, University of Queensland, Woolloongabba, Australia.; University of Queensland Centre for Clinical Research, Faculty of Medicine, University of Queensland, Herston, Australia.
Stanford CL; Department of Emergency Medicine, Gold Coast University Hospital, Southport, Australia.
McWhinney B; Department of Chemical Pathology, Pathology Queensland, Herston, Australia.
Ungerer J; Department of Chemical Pathology, Pathology Queensland, Herston, Australia.; Faculty of Biomedical Science, University of Queensland, St Lucia, Australia.
Roberts JA; Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, University of Queensland, Woolloongabba, Australia.; University of Queensland Centre for Clinical Research, Faculty of Medicine, University of Queensland, Herston, Australia.; Department of Pharmacy, Royal Brisbane and Women's Hospital, Brisbane, Australia.; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
Lipman J; University of Queensland Centre for Clinical Research, Faculty of Medicine, University of Queensland, Herston, Australia.; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Australia.; Division of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France.
Źródło:: European journal of clinical pharmacology [Eur J Clin Pharmacol] 2021 Feb; Vol. 77 (2), pp. 207-214. Date of Electronic Publication: 2020 Sep 24.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Original Publication: Berlin, New York, Springer.
MeSH Terms:: Anti-Bacterial Agents/*administration & dosage
Ceftriaxone/*administration & dosage
Sepsis/*drug therapy
Administration, Intravenous ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacokinetics ; Ceftriaxone/pharmacokinetics ; Critical Illness/therapy ; Drug Administration Schedule ; Emergency Service, Hospital ; Female ; Humans ; Male ; Middle Aged ; Models, Biological ; Monte Carlo Method ; Patient Admission ; Prospective Studies ; Sepsis/blood ; Sepsis/microbiology ; Treatment Outcome
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Contributed Indexing:: Keywords: Ceftriaxone; Dose; Pharmacokinetics; Sepsis
Substance Nomenclature:: 0 (Anti-Bacterial Agents)
75J73V1629 (Ceftriaxone)
Entry Date(s):: Date Created: 20200925 Date Completed: 20210906 Latest Revision: 20210906
Update Code:: 20240105
DOI:: 10.1007/s00228-020-03001-z
PMID:: 32974748
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Purpose: Unbound ceftriaxone pharmacokinetics in adult patients have been poorly characterised. The objective of this study is to determine the ceftriaxone dose that achieves an unbound trough concentration ≥ 0.5 mg/L in > 90% of adult patients receiving once-daily dosing presenting to the emergency department (ED) with sepsis.
Methods: We performed a prospective single-centre pharmacokinetic study. A single unbound plasma ceftriaxone concentration was obtained from each patient using blood collected as part of routine clinical practice within the first dosing interval. Samples were analysed using a validated ultra-high pressure liquid chromatography method. Population pharmacokinetic analysis and Monte Carlo simulations (n = 1000) were performed using Pmetrics for R.
Results: A ceftriaxone concentration obtained throughout the first dosing interval was available for fifty adult patients meeting sepsis criteria. Using this concentration time-curve data, a pharmacokinetic model was developed with acceptable predictive performance per the visual predictive check. Simulations show that a 1-g once-daily dose is unlikely to achieve the minimum therapeutic ceftriaxone exposure in > 90% patients with a creatinine clearance ≥ 60 mL/min. However, a 2-g once-daily dose will provide a therapeutic exposure for target pathogens infecting patients with a creatinine clearance ≤ 140 mL/min.
Conclusions: Ceftriaxone administered as a 1-g once-daily dose is unlikely to achieve a therapeutic exposure in > 90% of patients presenting to the ED with sepsis. Increasing the ceftriaxone dose to 2 g once daily will likely achieve the desired exposure against target pathogens. Future clinical trials are required to determine any potential clinical benefit of optimised ceftriaxone dosing.

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