Current Antibiotic Susceptibility Test Underestimates Minority Resistance: Implications for High-Risk Infections

Antibiotic susceptibility testing (AST) reports classify isolates as “susceptible” despite potential undetected resistant subpopulations—a phenomenon termed susceptibility heterogeneity (SH). Found in 15–97% of clinical isolates of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumoniae, SH arises from heteroresistance or polyclonal diversity and may evade standard low-inoculum protocols. Clinically, this can lead to treatment failure, particularly in high-risk cases including immunocompromised patients, bloodstream infections, transplant recipients, and situations where minor resistant subpopulations significantly affect outcome. We argue that ethical principles of non-maleficence, transparency, and equity now compel laboratories to acknowledge this limitation. A simple annotation—“Limited susceptibility possible; resistant subpopulations may not be detected”—should accompany “susceptible” results in immunocompromised patients. High-risk cases warrant enhanced testing. This commentary calls for zone inspection, staff training, and Clinical and Laboratory Standards Institute (CLSI)/European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline updates to reflect SH. Transparency enhances clinical decision-making without implying diagnostic fault.