title: Antibiotic dosing in multiple organ dysfunction syndrome.
abstract: 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.
authors.affiliation: Burns, Trauma and Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Critical Care Department, 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), Barcelona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Ulldemolins
authors.affiliation: 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, Herston, Brisbane, QLD, Australia; Pharmacy Department, Royal Brisbane and Women's Hospital, Herston, Brisbane, QLD, Australia.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
authors.affiliation: 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, Herston, Brisbane, QLD, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Critical Care Department, 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), Barcelona, Spain. Electronic address: jrello.hj23.ics@gencat.cat.
authors.forename: Jordi
authors.initials: J
authors.lastname: Rello
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000494:pharmacology; D016638:Critical Illness; D006801:Humans; D009102:Multiple Organ Failure / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents