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Updated: May 1, 2026
A High-throughput Compatible Assay to Evaluate Drug Efficacy against Macrophage Passaged Mycobacterium tuberculosis
Published on: March 24, 2017
New antituberculosis drugs, regimens, and adjunct therapies: needs, advances, and future prospects
Alimuddin I Zumla1, Stephen H Gillespie2, Michael Hoelscher3
1Centre for Clinical Microbiology, Division of Infection and Immunity, University College London, London, UK; University College London Hospitals NHS Foundation Trust, London, UK.
Abstract:
About 1·3 million people died of tuberculosis in 2012, despite availability of effective drug treatment. Barriers to improvements in outcomes include long treatment duration (resulting in poor patient adherence and loss of patients to follow-up), complex regimens that involve expensive and toxic drugs, toxic effects when given with antiretroviral therapy, and multidrug resistance. After 50 years of no antituberculosis drug development, a promising pipeline is emerging through the repurposing of old drugs, re-engineering of existing antibacterial compounds, and discovery of new compounds. A range of novel antituberculosis drugs are in preclinical development, several phase 2 and 3 trials are underway, and use of adjunct therapies is being explored for drug-sensitive and drug-resistant tuberculosis. Historical advances include approval of two new drugs, delamanid and bedaquiline. Combinations of new and existing drugs are being assessed to shorten the duration of therapy and to treat multidrug-resistant tuberculosis. There has also been progress in development of new antituberculosis drugs that are active against dormant or persister populations of Mycobacterium tuberculosis. In this Review, we discuss recent advances in antituberculosis drug discovery and development, clinical trial designs, laboratory methods, and adjunct host-directed therapies, and we provide an update of phase 3 trials of various fluoroquinolones (RIFAQUIN, NIRT, OFLOTUB, and REMoxTB). We also emphasise the need to engage the community in design, implementation, and uptake of research, to increase international cooperation between drug developers and health-care providers adopting new regimens.
Insights
New antituberculosis drugs are emerging to combat drug resistance and shorten treatment durations, offering hope against tuberculosis (TB). Research focuses on novel compounds, drug repurposing, and adjunct therapies to improve patient outcomes and overcome treatment barriers.
Area of Science:
- Infectious Diseases
- Pharmacology
- Public Health
Background:
- Tuberculosis (TB) caused 1.3 million deaths in 2012, with treatment challenges including long durations, complex regimens, drug toxicity, and multidrug resistance.
- A significant gap in antituberculosis drug development persisted for 50 years, hindering progress against this global health threat.
Purpose of the Study:
- To review recent advancements in antituberculosis drug discovery and development.
- To discuss novel clinical trial designs, laboratory methods, and adjunct therapies for both drug-sensitive and drug-resistant TB.
- To highlight the importance of community engagement and international cooperation in TB research and treatment adoption.
Main Methods:
- Review of preclinical and clinical trial data for novel antituberculosis agents.
- Analysis of emerging drug pipelines, including repurposed drugs, re-engineered compounds, and new chemical entities.
- Examination of adjunct therapies and host-directed strategies.
- Update on phase 3 trials for fluoroquinolones (RIFAQUIN, NIRT, OFLOTUB, REMoxTB).
Main Results:
- A promising pipeline of novel antituberculosis drugs is emerging, with candidates in preclinical development and active phase 2 and 3 trials.
- Two new drugs, delamanid and bedaquiline, have been approved, representing historical advances.
- Combinations of new and existing drugs are being evaluated to shorten therapy duration and treat multidrug-resistant TB.
- Progress has been made in developing drugs targeting dormant or persister Mycobacterium tuberculosis populations.
Conclusions:
- Recent scientific and clinical efforts are yielding a new generation of antituberculosis drugs and therapeutic strategies.
- Addressing treatment adherence, toxicity, and resistance requires innovative approaches, including shorter regimens and combination therapies.
- Community involvement and global collaboration are crucial for the successful implementation and uptake of new TB treatments.
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