Therapeutic drug monitoring (TDM) is a fundamental tool when administering drugs that have a limited dosage or high toxicity, which could endanger the lives of patients. To carry out this monitoring, one can use different biological fluids, including blood, plasma, serum, and urine, among others. The help of specialized methodologies for TDM will allow for the pharmacodynamic and pharmacokinetic analysis of drugs and help adjust the dose before or during their administration. Techniques that are more versatile and label free for the rapid quantification of drugs employ biosensors, devices that consist of one element for biological recognition coupled to a signal transducer. Among biosensors are those of the optical biosensor type, which have been used for the quantification of different molecules of clinical interest, such as antibiotics, anticonvulsants, anti-cancer drugs, and heart failure. This review presents an overview of TDM at the global level considering various aspects and clinical applications. In addition, we review the contributions of optical biosensors to TDM.

Due to the high bacterial resistance to antibiotics (AB), it has become necessary to adjust the dose aimed at personalized medicine by means of therapeutic drug monitoring (TDM). TDM is a fundamental tool for measuring the concentration of drugs that have a limited or highly toxic dose in different body fluids, such as blood, plasma, serum, and urine, among others. Using different techniques that allow for the pharmacokinetic (PK) and pharmacodynamic (PD) analysis of the drug, TDM can reduce the risks inherent in treatment. Among these techniques, nanotechnology focused on biosensors, which are relevant due to their versatility, sensitivity, specificity, and low cost. They provide results in real time, using an element for biological recognition coupled to a signal transducer. This review describes recent advances in the quantification of AB using biosensors with a focus on TDM as a fundamental aspect of personalized medicine.

In recent decades, antimicrobial resistance (AMR) has led to an increased use of therapeutic alternatives. Among these options, colistin continues to be an option for the treatment of multi-resistant (MDR) Gram-negative bacterial infections. However, due to its high toxicity (nephrotoxicity and neurotoxicity) and narrow therapeutic window, colistin treatment must be utilized carefully. Colistin-treated patients have been observed to have higher mortality due to inadequate therapeutic levels. The objective of this study was to estimate the difference in colistin plasma levels in critically ill patients, and its relationship to favorable or unfavorable clinical outcomes. This prospective observational study was conducted between September 2017 and June 2020 at the Universidad de La Sabana Clinic, in patients who had been treated with colistimethate sodium (CMS) for at least 72 h until day 7 of drug treatment in the critical care unit of a university hospital. There were no statistically significant differences in colistin levels between groups with favorable or unfavorable clinical outcomes (0.16 SD vs. 0.54 SD p-value = 0.167). There was higher mortality in patients with subtherapeutic levels (18% vs. 0%), and additionally, there was a greater rate of renal failure in the group with higher therapeutic levels (50% vs. 20.7%). Due to the loss of power of the study, we were unable to demonstrate a possible difference between colistin levels related to favorable or unfavorable clinical outcomes at day 7. However, we recommend further studies to evaluate the impact of measuring levels in terms of mortality and security.

More than 70% of bacteria are resistant to all or nearly all known antimicrobials, creating the need for the development of new types of antimicrobials or the use of “last-line” antimicrobial therapies for the treatment of multi-resistant bacteria. These antibiotics include Glycopeptide (Vancomycin), Polymyxin (Colistin), Lipopeptide (Daptomycin), and Carbapenem (Meropenem). However, due to the toxicity of these types of molecules, it is necessary to develop new rapid methodologies to be used in Therapeutic Drug Monitoring (TDM). TDM could improve patient outcomes and reduce healthcare costs by enabling a favorable clinical outcome. In this way, personalized antibiotic therapy emerges as a viable option, offering optimal dosing for each patient according to pharmacokinetic (PK) and pharmacodynamic (PD) parameters. Various techniques are used for this monitoring, including high-performance liquid chromatography (HPLC), gas chromatography-mass spectrometry (GC-MS), and immunoassays. The objective of this study is the development and characterization by ELISA of specific polyclonal antibodies for the recognition of the antibiotics Vancomycin (glycopeptide), Colistin (polymyxin), Daptomycin (lipopeptide), and Meropenem (carbapenem) for future applications in the monitoring of these antibiotics in different fluids, such as human plasma. The developed antibodies are capable of recognizing the antibiotic molecules with good detectability, showing an IC50 of 0.05 nM for Vancomycin, 7.56 nM for Colistin, 183.6 nM for Meropenem, and 13.82 nM for Daptomycin. These antibodies offer a promising tool for the precise and effective therapeutic monitoring of these critical antibiotics, potentially enhancing treatment efficacy and patient safety.

Background/Objectives: In the area of pharmacology and clinical research, it is necessary to use versatile technologies able to quantify last-line antibiotic molecules with high specificity and sensitivity. This article describes the development of two types of immunosensors based on amperometric and surface plasmon resonance (SPR) measurements and their applicability in the measurement/assessment of therapeutic drug monitoring (TDM) of four last-line antibiotics such as vancomycin, colistin, daptomycin and meropenem in human plasma. In this study, ligand immobilization by preconcentration assays, sensor surface regeneration, determination of sensitivity and correlation of plasma sample quantification results by HPLC were considered. Results: In the case of the electrochemical biosensor the IC50 values obtained were 3.49 μg/L for vancomycin (VAN), 5.44 μg/L for colistin (COL), 0.82 μg/L for meropenem (MER) and 5.10 μg/L for daptomycin (DAP). For the SPRi biosensor the LODs achieved were 19 ng/mL for VAN, 9 μg/L for COL, 12 μg/L for MER and 12.3 μg/L for DAP. Finally, both electrochemical biosensor and the SPRi optical biosensor showed that for the four antibiotics the standard deviations were less than 10% with respect to the HPLC results, with ranges for VAN between ~5–6 µg/mL, for COL ~0.2–0.7 µg/mL, for MER ~4.5–5.5 µg/mL and for DAP ~0.09–0.65 µg/mL. Conclusions: These kinds of biosensors provide a precise and sensitive strategy, together with real-time determination, to quantify last-line antibiotics, with working ranges like those shown by robust techniques such as HPLC and great potential for the clinic.

The interaction of mesenchymal stromal cells (MSC) in co-cultures with hematopoietic progenitor cells (HPC) in ex-vivo models induce the secretion of pro-inflammatory protein factors and influences HPC cell proliferation and differentiation processes. Different studies have shown the quantification of these biomarkers in other conditioned media using an ELISA and Luminex™ type immunoassay format. In this paper, we developed real-time quantification of biomarkers in conditioned media of these cells in co-cultures from bone marrow, umbilical cord blood, and Wharton's jelly sources using surface plasmon resonance imaging (SPRi). We show the detection and quantification of CCL2, CCL5, bFGF, IL-6, IL-8 and VEGF proteins with high sensitivity and specificity. SPRi can be used with a real-time analysis methodology and could be considered a tool for biomarker assays.