Burden of antimicrobial resistance: compared to what?

Abstract

Background 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. Findings 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 [S] 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 to use 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. Application of survival methods is preferred, considering competing events. Conclusions In conclusion, we advocate to estimate the burden of AMR using the no-infection and S-infection counterfactuals. The resulting numbers will provide policy-relevant information about the upper and lower bound of future interventions designed to control AMR. The counterfactuals should be applied in cohort studies, whereby selection of the unexposed cohorts should be based on exposure density sampling, applying methods avoiding time-dependent bias and confounding.