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Postgraduate Education Corner: CONTEMPORARY REVIEWS IN CRITICAL CARE MEDICINE |

Antibiotic Dosing in Multiple Organ Dysfunction Syndrome

Marta Ulldemolins, PharmD; Jason A. Roberts, PhD, BPharm(Hons); Jeffrey Lipman, MD; Jordi Rello, MD, PhD
Author and Funding Information

From the Burns, Trauma and Critical Care Research Centre (Drs Ulldemolins, Roberts, and Lipman), The University of Queensland, Brisbane, QLD, Australia; Critical Care Department (Drs Ulldemolins and Rello), Vall d’Hebron University Hospital, Vall d’Hebron Institut de Recerca (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica En Red de Enfermedades Respiratorias (CIBERES) (Drs Ulldemolins and Rello), Barcelona, Spain; and Department of Intensive Care Medicine (Drs Roberts and Lipman) and Pharmacy Department (Dr Roberts), Royal Brisbane and Women’s Hospital, Herston, Brisbane, QLD, Australia.

Correspondence to: Jordi Rello, MD, PhD, Critical Care Department, Vall d’Hebron University Hospital, Institut de Recerca Vall d’Hebron-UAB, Passeig de la Vall d’Hebron 119-129, 08035 Barcelona, Spain; e-mail: jrello.hj23.ics@gencat.cat


Funding/Support: Funded by the National Health and Medical Research Council of Australia [Project Grant 519702; Australian Based Health Professional Research Fellowship 569917 (to Dr Roberts)]; Australia and New Zealand College of Anaesthetists [ANZCA 06/037 and 09/032]; Queensland Health-Health Practitioner Research Scheme; Royal Brisbane and Women’s Hospital Research Foundation (to Drs Roberts and Lipman); and CIBERES [0606036], Agència de Gestió d’Ajuts Universitaris i de Recerca [09/SGR/1226], and Fondo de Investigación Sanitaria [07/90960] (to Drs Ulldemolins and Rello).

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (http://www.chestpubs.org/site/misc/reprints.xhtml).


© 2011 American College of Chest Physicians


Chest. 2011;139(5):1210-1220. doi:10.1378/chest.10-2371
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Although early and appropriate antibiotic therapy remains the cornerstone of success for the treatment of septic shock, few data exist to guide antibiotic dose optimization in critically ill patients, particularly those with multiple organ dysfunction syndrome (MODS). It is well known that MODS significantly alters the patient’s physiology, but the effects of these variations on pharmacokinetics have not been reviewed concisely. Therefore, the aims of this article are to summarize the disease-driven variations in pharmacokinetics and pharmacodynamics and to provide antibiotic dosing recommendations for critically ill patients with MODS. The main findings of this review are that the two parameters that vary with greatest significance in critically ill patients with MODS are drug volume of distribution and clearance. Disease- and clinician-driven changes lead to an increased volume of distribution and lower-than-expected plasma drug concentrations during the first day of therapy at least. Decreased antibiotic clearance is common and can lead to drug toxicity. In summary, “front-loaded” doses of antibiotic during the first 24 h of therapy should account for the likely increases in the antibiotic volume of distribution. Thereafter, maintenance dosing must be guided by drug clearance and adjusted to the degree of organ dysfunction.

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