Therapeutic drug monitoring of beta-lactams in critically ill patients: Proof of concept

Roberts, Jason A., Ulldemolins, Marta, Roberts, Michael S., McWhinney, Brett, Ungerer, Jacobus, Paterson, David L. and Lipman, Jeffrey (2010) Therapeutic drug monitoring of beta-lactams in critically ill patients: Proof of concept. International Journal of Antimicrobial Agents, 36 4: 332-339. doi:10.1016/j.ijantimicag.2010.06.008


Author Roberts, Jason A.
Ulldemolins, Marta
Roberts, Michael S.
McWhinney, Brett
Ungerer, Jacobus
Paterson, David L.
Lipman, Jeffrey
Title Therapeutic drug monitoring of beta-lactams in critically ill patients: Proof of concept
Formatted title
Therapeutic drug monitoring of β-lactams in critically ill patients: Proof of concept
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 0924-8579
1872-7913
Publication date 2010-10
Sub-type Article (original research)
DOI 10.1016/j.ijantimicag.2010.06.008
Volume 36
Issue 4
Start page 332
End page 339
Total pages 8
Editor A. M. Geddes
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Collection year 2011
Language eng
Formatted abstract
The extreme pharmacokinetic behaviour of drugs sometimes observed in critically ill patients poses a significant threat to the achievement of optimal antibiotic treatment outcomes. Scant information on β-lactam antibiotic therapeutic drug monitoring (TDM) is available. The objective of this prospective study was to evaluate the practicality and utility of a β-lactam TDM programme in critically ill patients. TDM was performed twice weekly on all eligible patients at a 30-bed tertiary referral critical care unit. Blood concentrations were determined by fast-throughput high-performance liquid chromatography (HPLC) assays and were available within 12 h of sampling. Dose adjustment was instituted if the trough or steady-state blood concentration was below 4–5×the minimum inhibitory concentration (MIC) or above 10×MIC. A total of 236 patients were subject to TDM over an 11-month period. The mean ± standard deviation age was 53.5 ± 18.3 years. Dose adjustment was required in 175 (74.2%) of the patients, with 119 of these patients (50.4%) requiring dose increases after the first TDM. For outcome of therapy, 206 (87.3%) courses resulted in a positive treatment outcome and there were 30 (12.7%) treatment failures observed including 14 deaths and 15 courses requiring escalation to broader-spectrum agents; 1 course was ceased due to an adverse drug reaction. Using binomial logistic regression, only an elevated Acute Physiology and Chronic Health Evaluation (APACHE) II score (P < 0.01) and elevated plasma creatinine concentration (P = 0.05) were found to be predictive of mortality. In conclusion, further research is required to determine definitively whether achievement of optimal β-lactam pharmacodynamic targets improves clinical outcomes.
© 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Keyword β-Lactam antibiotic
beta-Lactam antibiotic
Continuous infusion
Extended infusion
Bolus dosing
Adverse events
TDM
Pharmacokinetics
Pharmacodynamics
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Authors prepress title: "The Utility of Beta-lactam Therapeutic Monitoring in Critically Ill Patients: Proof of concept".

Document type: Journal Article
Sub-type: Article (original research)
Collections: UQ Centre for Clinical Research Publications
Official 2011 Collection
School of Medicine Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 110 times in Thomson Reuters Web of Science Article | Citations
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Created: Mon, 21 Mar 2011, 19:51:57 EST by Sia Athanasas on behalf of Anaesthesiology and Critical Care - RBWH