3.5 Comparators

When interpreting the health impact of AMR, it is essential to understand the comparator used in the analysis. There are two types of comparators that are commonly used, and these correspond to two distinct definitions of ‘counterfactual scenarios’: the antimicrobial-susceptible infection counterfactual and the AMR infection-free counterfactual. Recall that counterfactual scenarios are hypothetical situations used to understand what would have happened if a specific factor or event (like AMR infections) had not been present.

The antimicrobial-susceptible infection counterfactual

This comparator refers to an equivalent individual with the same infection but caused by the susceptible (rather than resistant) phenotype of the same bacteria. For example, to estimate the number of deaths due to 3GCR infections in a target population over a specified period of time, you would compare to otherwise equivalent individuals with third-generation cephalosporin-susceptible (3GCS) E. coli infection as your comparator.

The underlying assumption when using this comparator is that if resistant infections were prevented, then susceptible infections caused by the same bacterial species could take their place since both compete for the same ecological niche, the position that a bacterial species has within its environment.

The target AMR infection-free counterfactual

This comparator refers to an otherwise equivalent individual who does not have the AMR infection of interest. It includes people with no infections or with infections caused by other pathogens. For example, if you are estimating the number of deaths due to 3GCR infections in a target population over a specified period of time, your comparator group would include all otherwise equivalent individuals without 3GCR E. coli infection, including individuals without an infection and individuals with infections caused by Klebsiella pneumoniae, for example. In other words, this is a counterfactual that is ‘AMR pathogen(s) of interest-free’. Another term used in the literature is the ‘no infection’ counterfactual. It is important to note, however, that this refers specifically to the absence of infection from the AMR pathogen of interest and not of any infection.

The underlying assumption when using this comparator to quantify the impact of AMR infections is that the preventive strategy being considered does not exclusively affect the number or severity of susceptible infections.

There is an ongoing discussion about when to use one comparator over the other and when to use both. The key considerations are the type of intervention one has in mind to reduce the impact of AMR infections, and the underlying mechanism of interaction between AMR pathogens and susceptible pathogens. Details on the empirical evidence and underlying assumption of the two comparators are beyond the scope of this course, but you can follow the WHO attributable mortality protocol (and elsewhere in published literature) to read further. For this course you should just be aware of the two comparators and understand their underlying assumptions.