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Effect of Blood Product Resuscitation on Cefazolin Pharmacokinetics in Trauma Patients.
Fouad, Aliaa; Berry, Angela; Gates, Jonathan; Kuti, Joseph L; Keating, Jane J.
Afiliación
  • Fouad A; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
  • Berry A; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
  • Gates J; Division of Acute Care Surgery, Hartford Hospital, Hartford, Connecticut, USA.
  • Kuti JL; Department of Surgery, University of Connecticut School of Medicine, Farmington, Connecticut, USA.
  • Keating JJ; Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, Connecticut, USA.
Surg Infect (Larchmt) ; 25(6): 436-443, 2024 Aug.
Article en En | MEDLINE | ID: mdl-38995850
ABSTRACT

Background:

Antibiotics are frequently administered prophylactically to trauma patients with various injury patterns to prevent infectious complications. Trauma patients may also require large volume resuscitation with blood products. Limited data are available to support antibiotic dosing recommendations in this population. We hypothesized that we would be able to develop a population pharmacokinetic model of cefazolin, a frequently used antibiotic in the trauma scenario, from remnant blood samples by pharmacokinetic analysis of trauma patients.

Methods:

Remnant plasma from standard of care chemistry/hematology assessments was retrieved within 48 h of collection and assayed to determine cefazolin concentrations. Population pharmacokinetic analyses were conducted in Pmetrics using R. Linear regression was conducted to assess the effect of blood product resuscitation volume on cefazolin pharmacokinetic parameters.

Results:

Cefazolin concentrations best fitted a two-compartment model (Akaike information criterion 443.9). The mean ± standard deviation parameters were total body clearance (4.3 ± 1.9L), volume of the central compartment (Vc 7.7 ± 6.9L), and intercompartment transfer constants (k12 1.3 ± 0.98 h-1, k21 0.6 ± 0.45 h-1). No statistical relationships were observed between blood products, volume of blood products, and cefazolin clearance or Vc (R2 0.0004-0.21, p = 0.08-0.95). Using a 5,000-patient Monte Carlo simulation, 2 g with repeated dosing every 2 h until end of surgery was required to achieve 93.2% probability of 100% free time above the minimum inhibitory concentration (MIC) (fT > MIC) at the ECOFF value for Staphylococcus aureus (2 mg/L).

Conclusions:

In these 15 trauma patients receiving blood transfusion, no relationship with blood volume resuscitation and cefazolin pharmacokinetics was observed. On the basis of this pharmacokinetic model, frequent cefazolin doses are required to maintain 100% fT > MIC.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Heridas y Lesiones / Cefazolina / Antibacterianos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Surg Infect (Larchmt) Asunto de la revista: BACTERIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Heridas y Lesiones / Cefazolina / Antibacterianos Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Surg Infect (Larchmt) Asunto de la revista: BACTERIOLOGIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos