Abstract
Tuberculosis (TB) remains a global health emergency, with an estimated 2 billion people infected across the world, and 1.4 million people dying to this disease every year. Many aspects of the causative agent, Mycobacterium tuberculosis, make this disease difficult for healthcare and laboratory researchers to fight against, such as unique pathophysiology, latent infection and long and complex treatment regimens, thus causing patient non-compliance with the treatment. Development of new drugs is critical for tackling these problems. Repurposing drugs is a promising strategy for generating an effective drug treatment whilst circumventing many of the challenges of conventional drug development. In this regard, the incorporation of immunomodulatory drugs into the standard regimen to potentiate frontline drugs is found to be highly appealing. Drugs of diverse chemical classes and drug categories are increasingly being evidenced to possess antitubercular activity, both in vitro and in vivo. This article explores and discusses the molecular entities that have shown promise in being repurposed for use in anti-TB adjunctive therapy and aims to provide the most up-to-date picture of their progress.
Highlights
Despite the recent resurgence in political will to fight tuberculosis (TB), the disease remains as a leading cause of death from a single infectious agent around the world [1]
Moxifloxacin has been successfully repurposed as second-line treatment for TB [15], and several other fluoroquinolones are in clinical trials to shorten TB treatment or are in pre-clinical development [16], whilst novel derivatives from nitroimidazole, pretomanid and delamanid have been approved for use in TB patients and have numerous late clinical trials aiming to incorporate them into combination therapies [17]
While non-steroidal anti-inflammatory drug (NSAID) have a justified role due to their antimicrobial mechanisms of action in the proposed adjunctive therapy, the timing of administration and route of drug delivery would be critical in modulating the immune response appropriately
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The causative agent of TB is Mycobacterium tuberculosis, a slow-growing acid-fast bacillus manifesting itself primarily as a respiratory pathogen causing pulmonary disease It can cause extra-pulmonary TB via systemic infection, and its pathogens are capable of crossing the blood–brain barrier. The prospect of vaccines eradicating TB seems far into the future as the latest M72/AS01E vaccine only provides protection in half of those administered after three years [10], and efficacy of the BCG vaccine against adult pulmonary disease is highly disputed [11] It took an astonishing 40 years, after the golden era of antibiotic discovery, for an anti-TB drug with a completely unique mechanism of action to be developed and become approved by the FDA [12,13]. It is evident that the low-hanging fruit for novel antimicrobials has been long picked
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