Astúa Alejandro, Estevez Maria Carmen, Luque Sonia, Grau Santiago, Sorlí Luisa, Montero Milagro, Horcajada Juan P, Lechuga Laura M
Nanobiosensors and Bioanalytical Applications Group, Catalan Institute of Nanoscience and Nanotechnology (ICN2), CSIC, CIBER-BBN, BIST, Bellaterra 08193, Spain.
Pharmacy Service, Hospital del Mar, Hospital del Mar Research Institute, Universitat Pompeu Fabra (UPF), Barcelona 08003, Spain.
Anal Chem. 2025 Jun 17;97(23):12051-12059. doi: 10.1021/acs.analchem.4c06748. Epub 2025 Jun 3.
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 (-value < 0.001) and 0.7435 (-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.
创新的诊断工具可加强对抗生素的常规监测，从而改善由耐抗生素细菌引起的感染的管理。治疗药物监测（TDM）包括测量患者血液中的药物水平，以确保最佳疗效和安全性，特别是对于治疗指数（TI）较窄的药物，有助于控制剂量和管理毒性风险。阿米卡星（AK）和黏菌素（CS）是治疗多重耐药（MDR）细菌的关键抗生素，但它们有副作用，需要精确的TDM来尽量减少副作用。当前的分析技术，如免疫测定、高效液相色谱（HPLC）和液相色谱-质谱联用（LC-MS），是抗生素分析的金标准，但它们可能需要将人体样本转移到集中设施，从而延误关键结果和周转时间。相比之下，等离子体生物传感器在临床诊断方面具有优势，能够以最少的样本量和处理进行实时药物检测，非常适合即时检测应用。我们已采用等离子体生物传感器来定量并快速监测血液中阿米卡星和黏菌素的水平。这些生物传感器具有高特异性和灵敏度，血清中阿米卡星的检测限（LOD）为0.92 ng/mL（1.57 nM），黏菌素的检测限为9.11 pg/mL（7.88 pM）。统计分析表明，生物传感器评估结果与标准分析方法之间具有很强的相关性（阿米卡星和黏菌素的斯皮尔曼相关系数分别为0.9171（p值<0.001）和0.7435（p值 = 0.04））。此外，我们的等离子体生物传感器具有简单、便携和无需标记评估的特点，并具备多重检测能力。结果在20分钟内快速得出，加上最少的样本处理，提高了个性化TDM的可行性，支持可改善患者治疗效果的定制治疗策略。这项工作为创建一个集成的即时检测生物传感器平台奠定了基础，该平台可在临床环境中患者床边有效地实时对抗生素和其他药物进行TDM。
