Breakpoint Drift: A Hidden Confounder in Antimicrobial Resistance Surveillance?

Antimicrobial resistance (AMR) is a well-documented biological phenomenon driven by selective pressure from antimicrobial use. However, reported increases in AMR are influenced not only by microbial evolution but also by changing interpretive frameworks, particularly revisions to clinical breakpoints (MICs, zone diameters). These breakpoint shifts, introduced by organizations such as CLSI and EUCAST, can significantly alter resistance classifications without any change in microbial biology. Studies show that applying new breakpoints alone can markedly increase reported resistance rates, creating a risk of conflating methodological reclassification with genuine microbial adaptation.

This “breakpoint drift” has major implications for surveillance data, cumulative antibiograms, global burden estimates, and public health policy. Without annotation or adjustment, resistance trends may be misinterpreted, leading to unnecessary escalation to last-line antibiotics, misdirected investments, and flawed policy decisions.

Proposed solutions include:

• Routine annotation of AMR data with breakpoint metadata.

• Standardized nomenclature for breakpoint epochs (e.g., S[CLSI2012]).

• Retesting archived isolates with current breakpoints or modeling historical adjustments.

• Integration of breakpoint harmonization protocols into global burden modeling.

Conclusion
True AMR trends reflect both microbial evolution and diagnostic redefinitions. Recognizing and correcting for breakpoint drift is essential for accurate surveillance, sound policy, and effective stewardship. Misinterpreting rising resistance as purely biological risks undermining both clinical decision-making and global AMR response.