The MIC-Outcome Gap Explained

Single-cell imaging of 140 million bacteria reveals drug tolerance—not just resistance—drives mycobacterial treatment outcomes

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A new imaging method, Antimicrobial Single-Cell Testing (ASCT), predicts mycobacterial treatment outcomes more accurately than minimum inhibitory concentrations.
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ASCT demonstrated that drug tolerance is a heritable trait correlating with clinical failure, even in the absence of antibiotic resistance.
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In Mycobacterium tuberculosis, starvation conditions predicted treatment outcomes better than standard drug susceptibility testing.
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Heritability analysis revealed drug tolerance phenotypes are genetically determined, with estimates ranging from 32% to 97% across tested drugs.
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The study highlights the potential for ASCT to improve drug development and personalized therapy by linking in vitro killing to in vivo efficacy.

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