Achieving Ultrasensitive Chromogenic Probes for Rapid, Direct Detection of Carbapenemase-Producing Bacteria in Sputum

Carbapenemase-producing bacteria (CPB) stand as the most dangerous “superbugs” in the clinic. Rapid point-of-care (POC) detection of CPB in clinical samples is key to timely and effective infection management. We herein report the first ultrasensitive chromogenic probe that allows direct POC detection of CPB in clinical sputum samples at a sample-to-result time of less than 15 min. This chromogenic probe is modularly designed by conjugating the carbapenem core with a benzene derivative bearing an electronegativity-tunable substituent. Unexpectedly high sensitivity was achieved simply by choosing strong electron-withdrawing substituents, such as −N⁺(CH₃)₃, without resorting to complex molecular design. Through integrating the probes with a portable paper chip, 24 out of 80 clinical sputum samples from sepsis patients with lung infections were quickly diagnosed as CPB-positive, exhibiting 100% clinical sensitivity and specificity. This low-cost paper chip assay can be readily performed on-site, breaking through the dilemma of rapid CPB detection, especially in resource-limited settings.