The path of anti-tuberculosis drugs: from blood to lesions to mycobacterial cells

Abstract

Understanding the pharmacokinetic and pharmacodynamic properties of anti-tuberculosis drugs is crucial for designing more effective dosing regimens. In this Progress article, Véronique Dartois describes the methods that are available to monitor the distribution of drugs as they travel from the blood compartment to granulomatous lesions and penetrate infected immune cells to finally reach their intended targets inside mycobacterial cells. For the successful treatment of pulmonary tuberculosis, drugs need to penetrate complex lung lesions and permeate the mycobacterial cell wall in order to reach their intracellular targets. However, most currently used anti-tuberculosis drugs were introduced into clinical use without considering the pharmacokinetic and pharmacodynamic properties that influence drug distribution, and this has contributed to the long duration and limited success of current therapies. In this Progress article, I describe new methods to quantify and image drug distribution in infected lung tissue and in mycobacterial cells, and I explore how this technology could be used to design optimized multidrug regimens.