Bacterial wound infections can cause septicemia and lead to limb amputation or death. Therefore, early detection of bacteria is important in chronic wound management. Here, an optical biosensor based on porous silicon resonant microcavity (pSiRM) structure modified with fluorogenic peptide substrate is demonstrated to detect the presence of Sortase A (SrtA), a bacterial enzyme found in the cell membrane protein of Staphylococcus aureus. The combination of fluorescence enhancement effects of the pSiRM architecture with the incorporation of SrtA fluorogenic peptide substrate within the pSi matrix enables the sensing of SrtA with an outstanding limit of detection of 8 × 10-14 M. Modification of the pSiRM structure with microscale spots of two fluorogenic peptide substrates, one specific for SrtA and the other for matrix metalloproteinases, effectively demonstrates the feasibility to perform multiplexed biomarker analysis. The results in this study highlight the potential of the pSiRM sensing platform as a point-of-care diagnostic tool for biomarkers of bacterial wound infection.