Biosensor-enabled on-site therapeutic drug monitoring of antibiotics

Abstract

Antimicrobial resistance is increasing with an alarming rate for which the prime suspect is the “one size-fits-all” dosage strategies of antibiotics. Personalized antibiotherapy framework appears as a viable option to counteract inadequate dosage, as it offers the application of the optimal dosage regimen for each individual. Such individualized scheme, however, needs frequent sampling to tailor the blood antibiotic concentration to respond unique pharmacokinetic/pharmacodynamic (PK/PD) of the patient. Herein, there are two alternative paths for feasible therapeutic drug monitoring (TDM); transforming our understanding to utilize blood based sampling within the scope of point-of-care (POC), or focusing on non-invasive samples. Here, we present a versatile biosensor along with an antibody-free assay that can be utilized in both paths for on-site TDM. The developed platform is evaluated in a large animal study (pigs exposed with overdose, normal dose, and underdose of ß lactams), in which antibiotic concentrations are quantified in matrices including whole blood, plasma, urine, saliva, and exhaled breath condensate (EBC). Herein, the detection and the clearance of drug concentrations in EBC is demonstrated for the first time. Influence of the secretion mechanisms on measured drug concentrations is then quantified by comparing the plasma concentrations with those in EBC, saliva and urine. The potential of the developed platform for blood-based POC application is further illustrated by tracking ß lactam concentrations in untreated blood samples. Finally, multiplexing capabilities are explored successfully for multianalyte/sample analysis. Enabling a rapid, low-cost, sample-independent, and multiplexed on-site TDM, this system could pave the way for the personalized drug therapies and thus, shift the paradigm of “one size-fits-all” strategies.