How do I adjust antimicrobial daily dosage in patients with MODS? a pharmacist’s contribution

Ulldemolins, Marta and Roberts, Jason A. (2012). How do I adjust antimicrobial daily dosage in patients with MODS? a pharmacist’s contribution. In Jordi Rello, Jeffrey Lipman and Thiago Lisboa (Ed.), Sepsis management: PIRO and MODS (pp. 199-216) Berlin, Germany: Springer.


Author Ulldemolins, Marta
Roberts, Jason A.
Title of chapter How do I adjust antimicrobial daily dosage in patients with MODS? a pharmacist’s contribution
Title of book Sepsis management: PIRO and MODS
Place of Publication Berlin, Germany
Publisher Springer
Publication Year 2012
Sub-type Research book chapter (original research)
ISBN 9783642035197
3642035191
Editor Jordi Rello
Jeffrey Lipman
Thiago Lisboa
Chapter number 13
Start page 199
End page 216
Total pages 18
Total chapters 14
Collection year 2013
Language eng
Formatted Abstract/Summary Despite knowledge about the significant impact on positive clinical outcomes from early and appropriate antimicrobial therapy in the treatment of severe infections in critically ill patients, there is still little understanding of strategies for dose optimization in multiple organ dysfunction syndrome (MODS). With this chapter, we intend to review the disease-driven changes in antimicrobial pharmacokinetics and pharmacodynamics, and to provide antimicrobial dosing recommendations for critically ill patients with MODS.
From a pharmacokinetic viewpoint, the two main parameters that can be significantly altered in critically ill patients with MODS are the apparent volume of distribution (Vd) and clearance (CL). Most research in this area has described a larger Vd for many antimicrobials as well as impaired CL as the main pharmacokinetic consequences of MODS. The effects of an increased Vd for antimicrobials may be lower than expected plasma and tissue concentrations. However, decreased antimicrobial CL can lead to higher than expected concentrations, which may lead to high antimicrobial concentrations and possible drug toxicity. These pharmacokinetic changes may result in preventing the achievement of pharmacodynamic targets, resulting in suboptimal treatment.
A broad dosing principle to be considered for critically ill patients with MODS would be the administration of loading doses of antimicrobials during the first day of therapy to account for the likely increased Vd. This should occur even in the presence of organ dysfunction. Thereafter, maintenance dosing must be guided by CL and adjusted to the degree of organ dysfunction for the eliminating organ. Further research is still required to define dosing regimens that will facilitate optimal antimicrobial concentrations in MODS.
Q-Index Code BX
Q-Index Status Confirmed Code
Institutional Status UQ

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Created: Wed, 19 Sep 2012, 13:13:36 EST by Ms Ramona Hooyer on behalf of Anaesthesiology and Critical Care - RBWH