Challenging a dogma: antimicrobial susceptibility testing breakpoints for Mycobacterium tuberculosis

Area of Science:

• Microbiology
• Infectious Diseases
• Clinical Diagnostics

Background:

• Multidrug-resistant tuberculosis (MDR-TB) necessitates accurate antimicrobial susceptibility testing (AST).
• Current AST for Mycobacterium tuberculosis often lacks clinically meaningful and reproducible results.
• Established principles for bacterial and fungal susceptibility breakpoints have not been consistently applied to M. tuberculosis.

Purpose of the Study:

• To define wild-type minimum inhibitory concentration (MIC) distributions for M. tuberculosis.
• To evaluate current susceptibility breakpoints for antituberculosis agents.
• To recommend revisions for improved accuracy and reproducibility of AST.

Main Methods:

• Defined tentative wild-type MIC distributions for M. tuberculosis.
• Analyzed existing susceptibility breakpoints in relation to wild-type MICs and clinical data.
• Applied modern pharmacokinetic/pharmacodynamic and clinical outcome principles.

Main Results:

• Some existing breakpoints bisect wild-type distributions, causing poor reproducibility.
• Other breakpoints are set higher than wild-type MICs without clinical justification, potentially leading to false susceptibility reports.
• Tentative wild-type MIC distributions for M. tuberculosis have been established.

Conclusions:

• Susceptibility breakpoints for antituberculosis agents require systematic review and revision.
• Adopting modern breakpoint setting methodologies will enhance the accuracy and reproducibility of M. tuberculosis AST.
• Revised breakpoints are crucial for effective management of drug-resistant tuberculosis.