Improving tuberculosis treatment using mid-infrared spectroscopy for bedside therapeutic drug monitoring

Abstract

Rifampicin is an antimicrobial drug used to treat tuberculosis. The deterioration of a tuberculosis patient on rifampicin is a serious event with several possible causes. Rapid bedside measurement of rifampicin would enable clinicians to determine if patient deterioration was due to subtherapeutic levels and quickly correct the dosing. It would also support personalised dosing to maximise antimicrobial effectiveness whilst minimising side effects. The optimum therapeutic concentration range is 8 -24 mg/L. We report ATR-FTIR spectroscopy data for the detection of rifampicin for bedside therapeutic drug monitoring (TDM). We demonstrate a limit of detection of 0.46 mg/L from 20 μL spiked whole blood samples. Using whole blood directly enables bedside measurements because it does not require centrifugation and pipetting to extract plasma, which are generally performed in a central laboratory. The absorption-concentration response had good linearity (R 2 = 0.998) up to the highest measured concentration of 100 mg/L. We apply this data to the design of a miniaturised mid-infrared sensor for TDM using silicon photonics. We present an analysis of the optimum interaction length for an evanescent waveguide sensor using the absorption of rifampicin and a numerical model to quantify the contributions of different system and device noise sources. These sensors can be made more sensitive than their benchtop equivalent because of the enhanced evanescent electric field strength and the increased power spectral density of tunable quantum cascade lasers.