Therapeutic drug monitoring of β-lactams in critically ill patients: proof of concept

Roberts, Jason A.; Ulldemolins, Marta; Roberts, Michael S.; McWhinney, Brett; Ungerer, Jacobus; Paterson, David L.; Lipman, Jeffrey

doi:10.1016/j.ijantimicag.2010.06.008

« Previous Next »International Journal of Antimicrobial Agents
Volume 36, Issue 4 , Pages 332-339, October 2010

Therapeutic drug monitoring of β-lactams in critically ill patients: proof of concept

Jason A. Roberts
- Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
- Pharmacy Department, Royal Brisbane and Women's Hospital, Brisbane, Australia
- Department of Intensive Care, Royal Brisbane and Women's Hospital, Brisbane, Australia
- Corresponding author. Present address: Burns Trauma and Critical Care Research Centre, Level 3 Ned Hanlon Building, Royal Brisbane and Women's Hospital, Butterfield Street, Brisbane, Queensland 4029, Australia. Tel.: +61 7 3636 4108; fax: +61 7 3636 3542.
Marta Ulldemolins
- Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
- Critical Care Department, Vall d’Hebron University Hospital; Institut de Recerca Vall d’Hebron-Universitat Autònoma de Barcelona (UAB)-CIBER Enfermedades Respiratorias, Barcelona, Spain
Michael S. Roberts
- Therapeutics Research Unit, The University of Queensland, Brisbane, Australia
- School of Pharmacy, University of South Australia, Adelaide, Australia
Brett McWhinney
- Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia
Jacobus Ungerer
- Department of Chemical Pathology, Pathology Queensland, Royal Brisbane and Women's Hospital, Brisbane, Australia
David L. Paterson
- Department of Infectious Diseases, Royal Brisbane and Women's Hospital, Brisbane, Australia
- University of Queensland Centre for Clinical Research, The University of Queensland, Brisbane, Australia
Jeffrey Lipman
- Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, Australia
- Department of Intensive Care, Royal Brisbane and Women's Hospital, Brisbane, Australia

Received 16 May 2010; accepted 9 June 2010. published online 04 August 2010.

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 12h 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.