title: Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: A structured review.
abstract: The increased prevalence of obesity presents challenges for clinicians aiming to provide optimised antimicrobial dosing in the intensive care unit. Obesity is likely to exacerbate the alterations to antimicrobial pharmacokinetics when the chronic diseases associated with obesity exist with the acute pathophysiological changes associated with critical illness. The purpose of this paper is to review the potential pharmacokinetic (PK) changes of antimicrobials in obese critically ill patients and the implications for appropriate dosing. We found that hydrophilic antimicrobials (e.g. β-lactams, vancomycin, daptomycin) were more likely to manifest altered pharmacokinetics in critically ill patients who are obese. In particular for β-lactam antibiotics, obesity is associated with a larger volume of distribution (V(d)). In obese critically ill patients, piperacillin is also associated with a lower drug clearance (CL). For doripenem, these PK changes have been associated with reduced achievement of pharmacodynamic (PD) targets when standard drug doses are used. For vancomycin, increases in Vd are associated with increasing total body weight (TBW), meaning that the loading dose should be based on TBW even in obese patients. For daptomycin, an increased Vd is not considered to be clinically relevant. For antifungals, little data exist in obese critically ill patients; during fluconazole therapy, an obese patient had a lower V(d) and higher CL than non-obese comparators. Overall, most studies suggested that standard dosage regimens of most commonly used antimicrobials are sufficient to achieve PD targets. However, it is likely that larger doses would be required for pathogens with higher minimum inhibitory concentrations.
authors.affiliation: Burns, Trauma & Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia.
authors.forename: Abdulaziz S
authors.initials: AS
authors.lastname: Alobaid
authors.affiliation: Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Maya
authors.initials: M
authors.lastname: Hites
authors.affiliation: Burns, Trauma & Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Lipman
authors.affiliation: Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: Fabio Silvio
authors.initials: FS
authors.lastname: Taccone
authors.affiliation: Burns, Trauma & Critical Care Research Centre, The University of Queensland, Brisbane, QLD, Australia; Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia; School of Pharmacy, The University of Queensland, Brisbane, QLD, Australia. Electronic address: j.roberts2@uq.edu.au.
authors.forename: Jason A
authors.initials: JA
authors.lastname: Roberts
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics*; D016638:Critical Illness; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D009765:Obesity
chemical_list: D000890:Anti-Infective Agents
keywords: Antifungal; Fluconazole; Morbidly obese patients; Non-obese patients; Obesity; Pharmacodynamics