Journal
INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Volume 36, Issue 4, Pages 332-339Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijantimicag.2010.06.008
Keywords
beta-Lactam antibiotic; Continuous infusion; Extended infusion; Bolus dosing; Adverse events; TDM; Pharmacokinetics; Pharmacodynamics
Funding
- Burns Trauma and Critical Care Research Centre by the National Health and Medical Research Council of Australia [519702]
- Australia and New Zealand College of Anaesthetists (ANZCA) [06/037, 09/032]
- Queensland Health-Health Practitioner Research Scheme
- Royal Brisbane and Women's Hospital Research Foundation
- CIBERES, AGAUR [SGR05/520, FIS 07/90960]
- Australian National Health and Medical Research Council of Australia
- [569917]
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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 beta-lactam antibiotic therapeutic drug monitoring (TDM) is available. The objective of this prospective study was to evaluate the practicality and utility of a beta-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 4-5x the minimum inhibitory concentration (MIC) or above 10x 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 beta-lactam pharmacodynamic targets improves clinical outcomes. (C) 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
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