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Right Dose, Right Now: Customized Drug Dosing in the Critically Ill

Roberts, Jason A. PhD, FSHP; Kumar, Anand MD, FCCM; Lipman, Jeffrey MD, FCICM

doi: 10.1097/CCM.0000000000002210
Plenary Articles

Drugs are key weapons that clinicians have to battle against the profound pathologies encountered in critically ill patients. Antibiotics in particular are commonly used and can improve patient outcomes dramatically. Despite this, there are strong opportunities for further reducing the persisting poor outcomes for infected critically ill patients. However, taking these next steps for improving patient care requires a new approach to antibiotic therapy. Giving the right dose is highly likely to increase the probability of clinical cure from infection and suppress the emergence of resistant pathogens. Furthermore, in some patients with higher levels of sickness severity, reduced mortality from an optimized approach to antibiotic use could also occur. To enable optimized dosing, the use of customized dosing regimens through either evidence-based dosing nomograms or preferably through the use of dosing software supplemented by therapeutic drug monitoring data should be embedded into daily practice. These customized dosing regimens should also be given as soon as practicable as reduced time to initiation of therapy has been shown to improve patient survival, particularly in the presence of septic shock. However, robust data supporting these logical approaches to therapy, which may deliver the next step change improvement for treatment of infections in critically ill patients, are lacking. Large prospective studies of patient survival and health system costs are now required to determine the value of customized antibiotic dosing, that is, giving the right dose at the right time.

1Burns, Trauma and Critical Care Research Centre, School of Medicine, The University of Queensland, Brisbane, Queensland, Australia.

2Department of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia.

3Pharmacy Department, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia.

4Centre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia.

5Sections of Critical Care Medicine and Infectious Diseases, Health Sciences Centre/St. Boniface Hospital, Departments of Medicine, Medical Microbiology and Pharmacology, University of Manitoba, Winnipeg, Manitoba, Canada.

Dr. Roberts’ institution received funding from Merck Sharpe and Dohme (investigator initiated grant), Merck Sharpe and Dohme (lecture fees), and Astellas (consultancy). He disclosed other funding from bioMerieux (money paid to university for consultancy) and Infectopharm (money paid to university for advisory board). Dr. Roberts also disclosed off-label product use: drug dosing that may be outside the product label. The remaining authors have disclosed that they do not have any potential conflicts of interest.

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