A new perspective on antimicrobial therapeutic drug monitoring: Surface-enhanced Raman spectroscopy

Therapeutic drug monitoring (TDM) enables the personalization of treatment regimens, enhancing efficacy in combating infectious diseases while minimizing toxicity risks and reducing the potential for pathogenic resistance. However, existing TDM techniques still present certain limitations. Chromatographic analysis involves a prolonged detection period, which hampers its capacity for rapid multi-sample analysis. Immunoassay is constrained by poor specificity and stability, as well as a restricted range of detectable drugs. Surface-enhanced Raman spectroscopy (SERS) amplifies the Raman signals of target molecules via the local electromagnetic field and charge transfer effects on the surface of plasmonic materials, offering many significant advantages including high sensitivity, rapid detection, minimal sample requirements, and the ability to provide molecular fingerprints. SERS biosensing has demonstrated considerable potential in the field of blood drug concentration monitoring. This paper comprehensively reviews the research on the application of SERS in the TDM of antimicrobial agents. Beginning with the clinical practice of antimicrobial TDM, this review systematically introduces the principles of SERS techniques, the enhancement substrates, and the commonly used data processing methods including machine learning. It then provides a detailed discussion of the application of SERS in the TDM of various types of antimicrobials. Finally, it summarizes four major challenges currently faced by SERS techniques in antimicrobial TDM—namely protein corona effects, matrix interferences, substrate heterogeneity, and quantification reproducibility—and proposes potential future directions. This paper aims to offer new strategies and perspectives for the TDM and personalized dosage of antimicrobial agents.