Antimicrobial Dosing in Specific Populations and Novel Clinical Methodologies: Obesity.

Abstract

Obesity and its related comorbidities can negatively influence the outcomes of certain infectious diseases. Specific dosing recommendations are often lacking in the product label for patients with obesity that leads to unclear guidance in practice. Higher rates of therapeutic failure have been reported with some fixed dose antibiotics and pragmatic approaches to dose modification are limited for orally administered agents. For i.v. antimicrobials dosed on weight, alternate body size descriptors (ABSDs) have been used to reduce the risk of overdosing. These ABSDs are mathematical transformations of height and weight that represent fat-free weight and follow the same principles as body surface area (BSA)-based dosing of cancer chemotherapy. However, ABSDs are rarely studied in pivotal phase III studies and so can risk the underdosing of antimicrobials in patients with obesity when incorrectly applied in the real-world setting. Specific case examples are presented to highlight these risks. Although general principles may be considered by clinicians, a universal approach to dose modification in obesity is unlikely. Studies that can better distinguish human body phenotypes may help reduce our reliance on height and weight to define dosing. Simple and complex technologies exist to quantify individual body composition that could improve upon our current approach. Early evidence suggests that body composition parameters repurposed from medical imaging data may improve upon height and weight as covariates of drug clearance and distribution. Clinical trials that can integrate human body phenotyping may help us identify new approaches to optimal dose selection of antimicrobials in patients with obesity.