Review and evaluation of vancomycin dosing guidelines for obese individuals

ABSTRACT

Introduction

Vancomycin dosing decisions are informed by factors such as body weight and renal function. It is important to understand the impact of obesity on vancomycin pharmacokinetics and how this may influence dosing decisions. Vancomycin dosing guidelines use varied descriptors of body weight and renal function. There is uncertainty whether current dosing guidelines result in attainment of therapeutic targets in obese individuals.

Areas covered

Literature was explored using PubMed, Embase, and Google Scholar for articles from January 1980 to July 2021 regarding obesity-driven physiological changes, their influence on vancomycin pharmacokinetics and body size descriptors and renal function calculations in vancomycin dosing. Pharmacokinetic simulations reflective of international vancomycin dosing guidelines were conducted to evaluate the ability of using total, ideal, and adjusted body weight, as well as Cockcroft-Gault and CKD-EPI equations to attain an area-under-the-curve to minimum inhibitory concentration ratio (AUC₂₄/MIC) target (400–650) in obese individuals.

Expert opinion

Vancomycin pharmacokinetics in obese individuals remains debated. Guidelines that determine loading doses using total body weight, and maintenance doses adjusted based on renal function and adjusted body weight, may be most appropriate for obese individuals. Use of ideal body weight leads to subtherapeutic vancomycin exposure and underestimation of renal function.

KEYWORDS:

• BMI
• dosing
• guidelines
• obese
• obesity
• pharmacokinetics
• renal function
• vancomycin
• weight

Article highlights

• There is conflicting evidence on the effect of obesity-driven physiological changes on vancomycin pharmacokinetics and its influence on vancomycin dosing decisions in obese individuals.

• Vancomycin dosing guidelines around the world use different body weight descriptors and methods of estimating renal function and there is lack of consensus on optimal dosing strategies in the obese.

• Pharmacokinetic simulations of guideline-recommended dosage regimens can help inform optimal dosing strategies to increase vancomycin target attainment in obese individuals.

• Using total body weight to determine loading doses and adjusted body weight to determine maintenance doses may be most suitable to attain target vancomycin exposure in obese individuals.

• Development of evidence-based vancomycin dosing guidelines in the obese population is needed.

This box summarizes key points contained in the article.

Acknowledgments

The authors thank Jan-Willem Alffenaar, Miao Yan, Renly Lim and Ranita Kirubakaran for their assistance in sourcing and confirming international vancomycin dosing guidelines.

Disclosure statement

The authors have no relevant affiliations or financial involvement with any organisation or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

The Australian Government is acknowledged for supporting this research by awarding an Australian Government Research Training Program (RTP) PhD Scholarship to S Wong. Work undertaken by SE Reuter is with the financial support of Cancer Council’s Beat Cancer Project on behalf of its donors, the State Government through the Department of Health, and the Australian Government through the Medical Research Future Fund.