FTIR-Derived Feature Insights for Predicting Time-Dependent Antibiotic Resistance Progression

The progression of antibiotic resistance is increasingly recognized as a dynamic and time-dependent phenomenon, challenging conventional diagnostics that define resistance as a binary trait.

Biomolecules have fingerprints in Fourier-transform infrared spectroscopy (FTIR). The targeting of specific molecular groups, combined with principal component analysis (PCA) and machine learning algorithms (ML), enables the identification of bacteria resistant to antibiotics.

In this work, we investigate how effective classification depends on the use of different numbers of principal components, spectral regions, and defined resistance thresholds. Additionally, we explore how the time-dependent behavior of certain spectral regions (different biomolecules) may demonstrate behaviors that, independently, do not capture a complete picture of resistance development. FTIR spectra were obtained from Staphylococcus aureus exposed to azithromycin, trimethoprim/sulfamethoxazole, and oxacillin at sequential time points during resistance induction. Combining spectral windows substantially improved model performance, with accuracy reaching up to 96%, depending on the antibiotic and number of components. Early resistance patterns were detected as soon as 24 h post-exposure, and the inclusion of all three biochemical windows outperformed single-window models. Each spectral region contributed distinctively, reflecting biochemical remodeling associated with specific resistance mechanisms.

These results indicate that antibiotic resistance should be viewed as a temporally adaptive trajectory rather than a static state. FTIR-based biochemical profiling, when integrated with ML, enables projection of phenotypic transitions and supports real-time therapeutic decision-making. This strategy represents a shift toward adaptive antimicrobial management, with the potential to personalize interventions based on dynamic resistance monitoring through spectral biomarkers.