Lighting up Resistance: Rapid Antimicrobial Susceptibility Testing of Gram-Negative Bacteria in Bloodstream Infections Using an Aggregation-Induced Emission Bioprobe

Rapid and accurate antimicrobial susceptibility testing (AST) is crucial for guiding treatment and combating resistance. However, conventional ASTs are time-consuming and require pure colonies, delaying the initiation of targeted antimicrobial therapy. Herein, a novel AST based on an aggregation-induced emission luminogen (AIEgen), DATVP, which can directly assess the antimicrobial susceptibility of Gram-negative bacteria in positive blood cultures, is reported. DATVP specifically lights up Gram-negative bacteria with damaged cell membranes while showing no fluorescence in intact bacteria. The antimicrobial-induced fluorescence turn-on of DATVP is found to be fast (within 6 h) and sensitive, allowing for reliable determination of antimicrobial susceptibility. Using DATVP, a wash-free AST is developed and its performance was validated on clinical isolates. The DATVP-based AST showed high categorical agreement (84-95%) with the standard method while shortening the time-to-result from days to hours. This method represents a new paradigm in phenotypic AST, offering speed, simplicity, and direct applicability to patient samples, with the potential to enable timely and targeted antimicrobial treatment.