The carbapenem inoculum effect provides insight into the molecular mechanisms underlying carbapenem resistance in Enterobacterales .

(CRE) pose a significant threat to public health worldwide. Carbapenem resistance can occur through several molecular mechanisms, including enzymatic hydrolysis by carbapenemases and reduced influx via porin mutations. Knowing the mechanisms of resistance informs therapies and infection control measures to prevent further spread of these deadly pathogens. In a large collection of CRE isolates, we found that only carbapenemase-producing CRE exhibit an inoculum effect, in which their measured resistance varies markedly with cell density, which risks misdiagnosis. Measuring this inoculum effect, or integrating other data from routine antimicrobial susceptibility testing, enhances the detection of carbapenem resistance and thus paves the way for more effective strategies to combat this growing public health crisis.