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Lancet Infect Dis. 2014 Jun;14(6):498-509. doi: 10.1016/S1473-3099(14)70036-2. Epub 2014 Apr 24.

Individualised antibiotic dosing for patients who are critically ill: challenges and potential solutions.

Author information

1
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia. Electronic address: j.roberts2@uq.edu.au.
2
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia.
3
Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Department of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
4
Nijmegen Medical Centre, Radboud University, Nijmegen, Netherlands.
5
Department of Pediatrics, Cincinnati Children's Hospital Medical Center, University of Cincinnati, Cincinnati, OH, USA.
6
Faculty of Science, University of Manchester, Manchester, UK.
7
Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK.
8
Department of Pharmacy, Nyack Hospital, Nyack, NY, USA.
9
Laboratory of Applied Pharmacokinetics, University of Southern California, Los Angeles, CA, USA.
10
School of Pharmacy, University of Buffalo, Buffalo, NY, USA.
11
Institute for Therapeutic Innovation, College of Medicine, Department of Medicine, University of Florida, Gainesville, FL, USA.
12
Department of Pharmacy, Heidenheim Hospital, Heidenheim, Germany.
13
Center for Anti-Infective Agents, Vienna, Austria.
14
Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, USA.

Abstract

Infections in critically ill patients are associated with persistently poor clinical outcomes. These patients have severely altered and variable antibiotic pharmacokinetics and are infected by less susceptible pathogens. Antibiotic dosing that does not account for these features is likely to result in suboptimum outcomes. In this Review, we explore the challenges related to patients and pathogens that contribute to inadequate antibiotic dosing and discuss how to implement a process for individualised antibiotic therapy that increases the accuracy of dosing and optimises care for critically ill patients. To improve antibiotic dosing, any physiological changes in patients that could alter antibiotic concentrations should first be established; such changes include altered fluid status, changes in serum albumin concentrations and renal and hepatic function, and microvascular failure. Second, antibiotic susceptibility of pathogens should be confirmed with microbiological techniques. Data for bacterial susceptibility could then be combined with measured data for antibiotic concentrations (when available) in clinical dosing software, which uses pharmacokinetic/pharmacodynamic derived models from critically ill patients to predict accurately the dosing needs for individual patients. Individualisation of dosing could optimise antibiotic exposure and maximise effectiveness.

PMID:
24768475
PMCID:
PMC4181663
DOI:
10.1016/S1473-3099(14)70036-2
[Indexed for MEDLINE]
Free PMC Article

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