Therapeutic drug monitoring of amikacin and colistin in patients with multidrug-resistant gram-negative infections using a portable plasmonic biosensor

Abstract

Innovative diagnostic tools that enhance antibiotic routine monitoring can improve the management of infections caused by antibiotic-resistant bacteria. Therapeutic drug monitoring (TDM) involves measuring drug levels in the patient bloodstream to ensure optimal efficacy and safety, particularly for drugs with a narrow therapeutic index (TI), assisting in dosage control and toxicity risk management. Amikacin (AK) and colistin (CS) are crucial antibiotics for treating multidrug-resistant (MDR) bacteria but they have side effects that require a precise TDM to try to minimize them. Current analytical techniques like immunoassays, high-performance liquid chromatography (HPLC), and liquid chromatography-mass spectrometry (LC-MS) are gold standards for the antibiotic analysis, but they may require transferring the human samples to centralized facilities, delaying crucial results and turnaround time. In contrast, plasmonic biosensors offer advantages for clinical diagnostics, enabling real-time drug detection with minimal sample volume and processing, being ideal for point-of-care applications. We have implemented plasmonic biosensors to quantify and rapidly monitor blood levels of amikacin and colistin. The biosensors provide high specificity and sensitivity, with limits of detection (LOD) of 0.92 ng/mL (1.57 nM) for amikacin and 9.11 pg/mL (7.88 pM) for colistin in blood serum. Statistics analyses demonstrated a strong correlation between the biosensor evaluation and the standard analytical methods (Spearman's correlation coefficient of 0.9171 (p-value < 0.001) and 0.7435 (p-value = 0.04) for amikacin and colistin, respectively). Our plasmonic biosensors offer in addition, simplicity, portability, and label-free evaluation, with multiplexed capabilities. The rapid turnaround of results in under 20 min, coupled with minimal sample processing, enhances the feasibility of personalized TDM, supporting tailored treatment strategies that can improve patient outcomes. This work lays the foundation for creating an integrated point-of-care biosensor platform for effectively performing TDM of antibiotics and other drugs in real-time at the patient's bedside in clinical settings.