Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: a structured review

Alobaid, Abdulaziz S., Hites, Maya, Lipman, Jeffrey, Taccone, Fabio Silvio and Roberts, Jason A. (2016) Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: a structured review. International Journal of Antimicrobial Agents, 47 4: 259-268. doi:10.1016/j.ijantimicag.2016.01.009


Author Alobaid, Abdulaziz S.
Hites, Maya
Lipman, Jeffrey
Taccone, Fabio Silvio
Roberts, Jason A.
Title Effect of obesity on the pharmacokinetics of antimicrobials in critically ill patients: a structured review
Journal name International Journal of Antimicrobial Agents   Check publisher's open access policy
ISSN 1872-7913
0924-8579
Publication date 2016-04-01
Year available 2016
Sub-type Article (original research)
DOI 10.1016/j.ijantimicag.2016.01.009
Open Access Status Not Open Access
Volume 47
Issue 4
Start page 259
End page 268
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 2726 Microbiology (medical)
2736 Pharmacology (medical)
2725 Infectious Diseases
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). 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 V 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 V 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 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.
Formatted 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 (Vd). 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 Vd 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.
Keyword Antifungal
Fluconazole
Pharmacodynamics
Non-obese patients
Obesity
Morbidly obese patients
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID APP1044941
APP1099452
APP1048652
Institutional Status UQ

 
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