Burden of Antimicrobial Resistance: Compared to What?

There has been an increased focus on the public health burden of antimicrobial resistance (AMR). This raises conceptual challenges such as determining how much harm multi-drug resistant organisms do compared to what, or how to establish the burden. In this viewpoint we will present a counterfactual framework and provide guidance to harmonize methodologies and optimize study quality. In AMR burden studies, two counterfactual approaches have been applied; the harm of drug-resistant infections relative to the harm of the same, drug-susceptible, infections (susceptible-infection counterfactual) and the total harm of drug-resistant infections relative to a situation where such infections were prevented (no-infection counterfactual). We propose to use an intervention-based causal approach to determine the most appropriate counterfactual. We show that intervention scenarios, species of interest, and types of infections influence the choice of counterfactual. We recommend using purpose-designed cohort studies to apply this counterfactual framework, whereby the selection of cohorts (patients with drug-resistant, drug-susceptible and no-infection) should be based on matching on time to infection through exposure density sampling to avoid biased estimates.