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Better outcomes through continuous infusion of time-dependent antibiotics to critically ill patients?

Roberts, Jason Aa,b; Lipman, Jeffreya,c; Blot, Stijndef; Rello, Jordig

Current Opinion in Critical Care: August 2008 - Volume 14 - Issue 4 - p 390–396
doi: 10.1097/MCC.0b013e3283021b3a
Pharmacology, metabolism and nutrition: Edited by Stanley A. Nasraway

Purpose of review Increasing interest is being directed toward possible benefits associated with continuous infusion of time-dependent antibiotics such as β-lactams and vancomycin to critically ill patients. The background, emerging evidence and practical considerations associated with continuous infusions are discussed.

Recent findings One large retrospective cohort study has found clinical outcome benefits of administering a β-lactam antibiotic by extended infusion compared with bolus administration. This complements a smaller randomized controlled trial comparing continuous infusion and intermittent bolus administration. For vancomycin, clinical outcome benefits have only been shown in a ventilator-associated pneumonia cohort of critically ill patients. No clinical outcome studies have been conducted for other time-dependent antibiotics.

Summary Continuous infusion of vancomycin and β-lactam antibiotics enables faster and more consistent attainment of therapeutic levels compared with intermittent bolus dosing. Although the clinical benefits have not been conclusively shown at this time, compelling pharmacokinetic/pharmacodynamic support for continuous infusion nevertheless exists. Given that critically ill patients may develop very large volumes of distribution as well as supranormal drug clearances, individualized therapy through the use of therapeutic drug monitoring is required. A definitive determination of the relative clinical efficacy of intermittent bolus and continuous administration of β-lactams or vancomycin will only be achieved after a large-scale multicenter randomized controlled trial has been performed.

aBurns Trauma and Critical Care Research Centre, University of Queensland, Australia

bDepartment of Pharmacy, Royal Brisbane and Women's Hospital, Australia

cDepartment of Intensive Care Medicine, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia

dDepartment of Infectious Diseases, Ghent University Hospital, Belgium

eFaculty of Healthcare, University College Ghent, Belgium

fFaculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

gCritical Care Department, Joan XXIII University Hospital, University Rovira & Virgili, Pere Virgili Health Institut, CiBER ENFERMEDADES RESPIRATORIAS (CIBERes) Carrer Mallafre Guasch, Tarragona, Spain

Correspondence to Jordi Rello, Critical Care Department, Joan XXIII University Hospital, Mallafre Guasch 4, 43007 Tarragona, Spain Tel: +34 977295818; fax: +34 977295878; e-mail:

© 2008 Lippincott Williams & Wilkins, Inc.