Abstract:Accurate and timely identification of hospital outbreak clusters is crucial for preventing the spread of infections that have epidemic potential. While assessing pathogen similarity through whole genome sequencing (WGS) is considered the gold standard for outbreak detection, its high cost and lengthy turnaround time preclude routine implementation in clinical laboratories. We explore the utility of two rapid and cost-effective alternatives to WGS, matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry and antimicrobial resistance (AR) patterns. We develop a machine learning framework that extracts informative representations from MALDI-TOF spectra and AR patterns for outbreak detection and explore their fusion. Through multi-species analyses, we demonstrate that in some cases MALDI-TOF and AR have the potential to reduce reliance on WGS, enabling more accessible and rapid outbreak surveillance.