DALI: defining antibiotic levels in intensive care unit patients. Are current beta-lactam antibiotic doses sufficient for critically ill patients?

Roberts, Jason A., Paul, Sanjoy K., Akova, Murat, Bassetti, Matteo, De Waele, Jan J., Dimopoulos, George, Kaukonen, Kirsi-Maija, Koulenti, Despoina, Martin, Claude, Montravers, Philippe, Rello, Jordi, Rhodes, Andrew, Starr, Therese, Wallis, Steven C. and Lipman, Jeffrey (2014) DALI: defining antibiotic levels in intensive care unit patients. Are current beta-lactam antibiotic doses sufficient for critically ill patients?. Clinical Infectious Diseases, 58 8: 1072-1083. doi:10.1093/cid/ciu027

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Author Roberts, Jason A.
Paul, Sanjoy K.
Akova, Murat
Bassetti, Matteo
De Waele, Jan J.
Dimopoulos, George
Kaukonen, Kirsi-Maija
Koulenti, Despoina
Martin, Claude
Montravers, Philippe
Rello, Jordi
Rhodes, Andrew
Starr, Therese
Wallis, Steven C.
Lipman, Jeffrey
Title DALI: defining antibiotic levels in intensive care unit patients. Are current beta-lactam antibiotic doses sufficient for critically ill patients?
Formatted title
DALI: defining antibiotic levels in intensive care unit patients. Are current β-lactam antibiotic doses sufficient for critically ill patients?
Journal name Clinical Infectious Diseases   Check publisher's open access policy
ISSN 1058-4838
1537-6591
Publication date 2014-04-15
Sub-type Article (original research)
DOI 10.1093/cid/ciu027
Open Access Status
Volume 58
Issue 8
Start page 1072
End page 1083
Total pages 12
Place of publication Cary, NC, United States
Publisher Oxford University Press
Collection year 2015
Language eng
Formatted abstract
Background. Morbidity and mortality for critically ill patients with infections remains a global healthcare problem. We aimed to determine whether β-lactam antibiotic dosing in critically ill patients achieves concentrations associated 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 pharmacokinetic/pharmacodynamic targets were free antibiotic concentrations above the minimum inhibitory concentration (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 (interquartile 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 exposure; a paradigm change to more personalized antibiotic dosing may be necessary to improve outcomes for these most seriously ill patients.
Keyword Continuous infusion
Extended infusion
Adverse events
Pharmacokinetics
Pharmacodynamics
Antibiotic
Intensive care
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Public Health Publications
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 123 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 128 times in Scopus Article | Citations
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Created: Fri, 11 Apr 2014, 16:48:54 EST by Professor Jeffrey Lipman on behalf of Anaesthesiology and Critical Care - RBWH