Rapid and precise treatment selection for antimicrobial-resistant infection enabled by a nano-dilution SlipChip

Antimicrobial resistance (AMR) has become an increasingly severe threat to global health, and AMR-associated infection is one of the leading causes of death around the world. Due to the long turnaround time and the limited flexibility and availability of current antimicrobial susceptibility testing (AST) methods, a large portion of patients with bacterial infections are still treated empirically, increasing the risk of mistreatment. To address the demand for precision treatment of bacterial infections, we developed a nano-dilution SlipChip (nd-SlipChip)-based systematic evaluation method, which facilitates rapid, logic feedback for the assessment of antibiotics, antibiotic combinations, and phage therapy. The nd-SlipChip can conveniently generate a microdroplet array with serially diluted antibiotics and determine the minimal inhibitory concentration (MIC) within 2 h by monitoring bacterial growth profiles, facilitating timely treatment selection. We demonstrated this method for 24 clinical isolates, including gram-negative bacteria (Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii) and gram-positive bacteria (Staphylococcus aureus). Three clinical isolates performed the second-stage antibiotic combinations screening, and effective combination therapies were identified for two of them. The remaining isolate proceeded to third-stage phage screening, where suitable phages were successfully selected. The nd-SlipChip provides a rapid and systematic approach for the precise selection of therapies targeting bacterial infections.