Tuberculosis drug development: progress, challenges, and the road ahead.

摘要

Tuberculosis (TB) drug development has made substantial progress in the past decade. There are currently at least ten drugs being evaluated in clinical trials. Some belong to chemical classes already employed in first- or second-line treatment regimens and are being explored for more optimized use at higher doses or in new drug combinations (rifamycins, fluoroquinolones and oxazolidinones), while others represent potential novel members of the TB drug arsenal, killing Mycobacterium tuberculosis through previously untried mechanisms of action (nitroimidazoles, diarylquinolines, ethylene diamines and pyrroles). The typical challenges of drug development are augmented in TB by the complexity of the disease, the requirement for multi-drug regimens, the relative lack of TB drug development for the past several decades, and inadequate resources being brought to bear despite the urgency of the global medical need. Yet in the face of these challenges, for the first time in history, there is a robust enough pipeline of drugs in development to potentially enable identification of a novel, three-drug regimen capable of curing patients in three months or less, whether they are infected with a strain of M. tuberculosis sensitive or resistant to the current first and second-line drugs. Realizing this potential will require innovation, persistence, cooperation and resources. A fine balance will need to be achieved between protecting novel drugs so that resistance to them doesn't develop and ensuring the regimens are low in cost, readily available, and adopted by healthcare systems and providers.