Normalized resistance interpretation as a tool for establishing epidemiological MIC susceptibility breakpoints

Area of Science:

• Microbiology
• Pharmacology
• Computational Biology

Background:

• Antimicrobial resistance necessitates accurate interpretation of Minimum Inhibitory Concentration (MIC) distributions.
• Existing methods may not fully capture the wild-type population, impacting resistance surveillance.
• The European Committee on Antimicrobial Susceptibility Testing (EUCAST) provides valuable MIC distribution data.

Purpose of the Study:

• To introduce and validate a novel method, Normalized Resistance Interpretation (NRI), for reconstructing wild-type MIC distributions.
• To assess the performance of NRI by comparing its derived cutoff values with EUCAST ECOFF values.
• To evaluate NRI's utility for Staphylococcus aureus and Escherichia coli across multiple antimicrobial agents.

Main Methods:

• Normalized Resistance Interpretation (NRI) was adapted for MIC distributions using helper variables.
• NRI was applied to 54 MIC distributions (27 antimicrobials for S. aureus and E. coli) from EUCAST.
• Cutoff values were calculated at +2.0 and +2.5 standard deviations (SD) above the mean and compared to EUCAST ECOFF values.

Main Results:

• NRI successfully generated normalized MIC distributions for all tested datasets.
• NRI's +2.0 SD cutoff values demonstrated strong agreement with EUCAST ECOFF values for both S. aureus and E. coli.
• Specifically, 26/27 and 25/27 distributions for S. aureus and E. coli, respectively, were within ±1 dilution step of ECOFF values.

Conclusions:

• NRI provides an objective and effective method for reconstructing wild-type populations within MIC distributions.
• This approach offers a valuable new tool for comparative antimicrobial susceptibility studies and laboratory quality control.
• NRI enhances global resistance surveillance and supports accurate antimicrobial susceptibility testing.