Bacterial and fungal infections persistently plague society and have amounted to one of the most prevalent issues in healthcare today. Thus, significant research effort is directed towards developing rapid diagnostic techniques for determination of the correct antibiotic (or antifungal) for a patient-tailored therapy. We have developed a rapid phenotypic antimicrobial susceptibility testing (AST) in which photonic 2D silicon microarrays are employed as both the optical transducer element and as a preferable solid−liquid interface for bacterial/fungal colonization. We harness the intrinsic ability of the micro-architectures to relay optical phase-shift reflectometric interference spectroscopic measurements (termed PRISM) and incorporate it into a platform for culture-free, label-free tracking of bacterial/fungal colonization, proliferation, and death. For example, bacteria proliferation within the microtopologies results in an increase in refractive index of the medium, yielding an increase in optical path difference, while cell death or bacteriostatic activity results in decreasing or unchanged values. The optical responses of bacteria, including clinical isolates and samples derived from patients at neighboring hospitals, to various concentrations of relevant antibiotics are tracked in real time, allowing for accurate determination of the minimum inhibitory concentration (MIC) values within 2-3 hours in comparison to assay times of <8 hours (using standard broth microdilution techniques or state-of-the-art clinical automated systems. This has opened the door to the observation of unique bacterial behaviors, as we can evaluate bacterial adhesion, growth, and antibiotic resistance on different micro-architectures, different surface chemistries, and even different strains. Motility, charge, and biofilm abilities have been explored for their effect of bacterial adhesion to the microstructures as we further develop our method of rapid, label-free AST for full clinical application.