The combination of Deep Learning techniques and Raman spectroscopy shows great potential offering precise and prompt identification of pathogenic bacteria in clinical settings. However, the traditional closed-set classification approaches assume that all test samples belong to one of the known pathogens, and their applicability is limited since the clinical environment is inherently unpredictable and dynamic, unknown or emerging pathogens may not be included in the available catalogs. We demonstrate that the current state-of-the-art Neural Networks identifying pathogens through Raman spectra are vulnerable to unknown inputs, resulting in an uncontrollable false positive rate. To address this issue, first, we developed a novel ensemble of ResNet architectures combined with the attention mechanism which outperforms existing closed-world methods, achieving an accuracy of 87.8±0.1% compared to the best available modelâ\euro™s accuracy of 86.7 ± 0.4%. Second, through the integration of feature regularization by the Objectosphere loss function, our model achieves both high accuracy in identifying known pathogens from the catalog and effectively separates unknown samples drastically reducing the false positive rate. Finally, the proposed feature regularization method during training significantly enhances the performance of out-ofdistribution detectors during the inference phase improving the reliability of the detection of unknown classes. Our novel algorithm for Raman spectroscopy enables the detection of unknown, uncatalogued, and emerging pathogens providing the flexibility to adapt to future pathogens that may emerge, and has the potential to improve the reliability of Raman-based solutions in dynamic operating environments where accuracy is critical, such as public safety applications.Â