DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically Ill Patients?

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Abstract

Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare prob- lem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations as- sociated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharma- cokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentra- tion (MIC) of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (inter- quartile range [IQR], 48–73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14–24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic ex- posure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.
Lingua originaleEnglish
pagine (da-a)1072-1083
Numero di pagine12
RivistaClinical Infectious Diseases
Volume58
Stato di pubblicazionePublished - 2014

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Lactams
Critical Illness
Intensive Care Units
Anti-Bacterial Agents
Microbial Sensitivity Tests
Pharmacokinetics
Odds Ratio
APACHE
Infection
Cross-Sectional Studies

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)
  • Infectious Diseases

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title = "DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically Ill Patients?",
abstract = "Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare prob- lem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations as- sociated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharma- cokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentra- tion (MIC) of the pathogen at both 50{\%} (50{\%} f T>MIC) and 100{\%} (100{\%} f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (inter- quartile range [IQR], 48–73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14–24), and 65{\%} of patients were male. Of the 248 patients treated for infection, 16{\%} did not achieve 50{\%} f T>MIC and these patients were 32{\%} less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50{\%} f T>MIC and 100{\%} f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic ex- posure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.",
author = "Antonino Giarratano and Andrea Cortegiani and Raineri, {Santi Maurizio}",
year = "2014",
language = "English",
volume = "58",
pages = "1072--1083",
journal = "Clinical Infectious Diseases",
issn = "1058-4838",
publisher = "Oxford University Press",

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TY - JOUR

T1 - DALI: Defining Antibiotic Levels in Intensive Care Unit Patients: Are Current β-Lactam Antibiotic Doses Sufficient for Critically Ill Patients?

AU - Giarratano, Antonino

AU - Cortegiani, Andrea

AU - Raineri, Santi Maurizio

PY - 2014

Y1 - 2014

N2 - Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare prob- lem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations as- sociated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharma- cokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentra- tion (MIC) of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (inter- quartile range [IQR], 48–73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14–24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic ex- posure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.

AB - Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare prob- lem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations as- sociated with maximal activity and whether antibiotic concentrations affect patient outcome.Methods. This was a prospective, multinational pharmacokinetic point-prevalence study including 8 β-lactam antibiotics. Two blood samples were taken from each patient during a single dosing interval. The primary pharma- cokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentra- tion (MIC) of the pathogen at both 50% (50% f T>MIC) and 100% (100% f T>MIC) of the dosing interval. We used skewed logistic regression to describe the effect of antibiotic exposure on patient outcome.Results. We included 384 patients (361 evaluable patients) across 68 hospitals. The median age was 61 (inter- quartile range [IQR], 48–73) years, the median Acute Physiology and Chronic Health Evaluation II score was 18 (IQR, 14–24), and 65% of patients were male. Of the 248 patients treated for infection, 16% did not achieve 50% f T>MIC and these patients were 32% less likely to have a positive clinical outcome (odds ratio [OR], 0.68; P = .009). Positive clinical outcome was associated with increasing 50% f T>MIC and 100% f T>MIC ratios (OR, 1.02 and 1.56, respectively; P < .03), with significant interaction with sickness severity status.Conclusions. Infected critically ill patients may have adverse outcomes as a result of inadeqaute antibiotic ex- posure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.

UR - http://hdl.handle.net/10447/100968

M3 - Article

VL - 58

SP - 1072

EP - 1083

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

ER -