Tuberculosis drug development: History and evolution of the mechanism-based paradigm

Abstract

Modern tuberculosis (TB) chemotherapy is widely viewed as a crowning triumph of antiinfectives research. However, only one new TB drug has entered clinical practice in the past 40 years while drug resistance threatens to further destabilize the pandemic. Here, we review a brief history of TB drug development, focusing on the evolution of mechanism(s)-of-action studies and key conceptual barriers to rational, mechanism-based drugs.