Aliaa Fouad, Angela Berry, Jonathan Gates, Joseph L Kuti, Jane J Keating
{"title":"Effect of Blood Product Resuscitation on Cefazolin Pharmacokinetics in Trauma Patients.","authors":"Aliaa Fouad, Angela Berry, Jonathan Gates, Joseph L Kuti, Jane J Keating","doi":"10.1089/sur.2023.341","DOIUrl":null,"url":null,"abstract":"<p><p><b><i>Background:</i></b> 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. <b><i>Methods:</i></b> 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. <b><i>Results:</i></b> 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 (V<sub>c</sub>: 7.7 ± 6.9L), and intercompartment transfer constants (k<sub>12</sub>: 1.3 ± 0.98 h<sup>-1</sup>, k<sub>21</sub>: 0.6 ± 0.45 h<sup>-1</sup>). No statistical relationships were observed between blood products, volume of blood products, and cefazolin clearance or V<sub>c</sub> (<i>R</i><sup>2</sup>: 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) (<i>f</i>T > MIC) at the ECOFF value for <i>Staphylococcus aureus</i> (2 mg/L). <b><i>Conclusions:</i></b> 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% <i>f</i>T > MIC.</p>","PeriodicalId":22109,"journal":{"name":"Surgical infections","volume":null,"pages":null},"PeriodicalIF":1.4000,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Surgical infections","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/sur.2023.341","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/7/12 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍:
Surgical Infections provides comprehensive and authoritative information on the biology, prevention, and management of post-operative infections. Original articles cover the latest advancements, new therapeutic management strategies, and translational research that is being applied to improve clinical outcomes and successfully treat post-operative infections.
Surgical Infections coverage includes:
-Peritonitis and intra-abdominal infections-
Surgical site infections-
Pneumonia and other nosocomial infections-
Cellular and humoral immunity-
Biology of the host response-
Organ dysfunction syndromes-
Antibiotic use-
Resistant and opportunistic pathogens-
Epidemiology and prevention-
The operating room environment-
Diagnostic studies