Definitions of S, I and R

EUCAST in 2019 changed the definitions of susceptibility testing categories S, I and R as shown below. Results of several consultations on the new definitions are available on the EUCAST website under “Consultations”.

• S - Susceptible, standard dosing regimen: A microorganism is categorised as "Susceptible, standard dosing regimen", when there is a high likelihood of therapeutic success using a standard dosing regimen of the agent.
• I - Susceptible, increased exposure*: A microorganism is categorised as "Susceptible, Increased exposure*" when there is a high likelihood of therapeutic success because exposure to the agent is increased by adjusting the dosing regimen or by its concentration at the site of infection.
• R - Resistant: A microorganism is categorised as "Resistant" when there is a high likelihood of therapeutic failure even when there is increased exposure.

 

*Exposure is a function of how the mode of administration, dose, dosing interval, infusion time, as well as distribution and excretion of the antimicrobial agent will influence the infecting organism at the site of infection.

 

The change has wide implications for microbiological routine laboratories, clinical reporting and advice and antimicrobial resistance surveillance. The tradition to lump I and R together as "non-susceptible" is no longer valid. Lumping categories together is best avoided. Per cent resistance (%R) will adequately describe resistance development and %S and %I (both susceptible categories) are best listed separately or lumped together under a heading of "susceptible". 

To help understand and use the new S, I and R definitions and the ATUs in the clinical laboratory, EUCAST has published the following:

• 3-page information to clinical colleagues
• EUCAST explanatory video (22 minutes) on the new definitions of S, I and R and on the use of the Area of Technical Uncertainty (ATU).
• In late 2020 there were EUCAST online seminars on how to implement and use the new susceptibility categories and on the use of the ATU in clinical laboratories. 
• To facilitate implementation of the definitions EUCAST has developed a powerpoint presentation for NACs to translate (currently available in Spanish / Czech / Serbian): 
  • The implementation of the new definitions of S, I and R (PDF file)  
  • The implementation of the new definitions of S, I and R (PPT-file)
• How to handle the ATU in clinical laboratories is described in a EUCAST guidance document.

Terminology

• Susceptible categories: S and I
• Resistant category: R
• Report isolates S, I or R. Where tables list "-", avoid testing and if a report is necessary, report "R".
• Describe isolates as belonging to the S, I or R categories.
• When an isolate is described as susceptible, this includes S and I but excludes R
• When an isolate is described as resistant, this excludes both susceptible categories (S and I).
• For surveillance purposes, avoid lumping categories – record as S, I and R. If lumping does occur, never lump I and R, only S and I. 

Wild type distributions and ECOFFs

• Wild type organisms: a micro-organism is defined as wild type (WT) for a species by the absence of phenotypically detectable resistance mechanisms to the drug in question
• Wild type and non-wild type organisms may or may not respond to clinically to treatment with the agent in question.
• The highest MIC-value (corresponding to the lowest zone diameter distribution value) of the wild type population is designated the epidemiological cut-off value (ECOFF)
• When calculated on many distributions, the ECOFF is stable, and will not change over time. This is contrary to clinical breakpoints which may change with new clinical data and experience.