Recent Progress and Challenges for Drug-Resistant Tuberculosis Treatment

Abstract

Control of Mycobacterium tuberculosis infection continues to be an issue, particularly in countries with a high tuberculosis (TB) burden in the tropical and sub-tropical regions. The effort to reduce the catastrophic cost of TB with the WHO’s End TB Strategy in 2035 is still obstructed by the emergence of drug-resistant TB (DR-TB) cases as result of various mutations of the MTB strain. In the approach to combat DR-TB, several potential antitubercular agents were discovered as inhibitors for various existing and novel targets. Host-directed therapy and immunotherapy also gained attention as the drug-susceptibility level of the pathogen can be reduced due to the pathogen’s evolutionary dynamics. This review is focused on the current progress and challenges in DR-TB treatment. We briefly summarized antitubercular compounds that are under development and trials for both DR-TB drug candidates and host-directed therapy. We also highlighted several problems in DR-TB diagnosis, the treatment regimen, and drug discovery that have an impact on treatment adherence and treatment failure.

Ethionamide and Prothionamide Based Coumarinyl-Thiazole Derivatives: Synthesis, Antitubercular Activity, Toxicity Investigations and Molecular Docking Studies

“…The DprE1 enzyme is a new validated target to develop novel anti-TB agents [ 2 ]. BTZ043 and macozinone are DprE1 inhibitors, which are in a clinical trial [ 2 , 21 ]. Like MIC value data, the DS and the RMSD values were also statistically significant ( p -values and CI 99% values).…”

Exploration of Isoxazole‐Carboxylic Acid Methyl Ester Based 2‐Substituted Quinoline Derivatives as Promising Antitubercular Agents

“…of 14,000 pills/complete course [3] . Startling increase in extremely drug resistant TB (XDR‐TB: MDR+resistant to fluoroquinolones+newer drugs bedaquiline/linezolid), has made already grim situation even more complicated [4] . Besides, adverse effects of prolonged treatment regimen, less effective and more toxic 2 nd line drugs, drug‐drug interaction along with untreatable dormant or latent strains of Mtb further adds to the TB disease burden [5,6] .…”

“…[3] Startling increase in extremely drug resistant TB (XDR-TB: MDR + resistant to fluoroquinolones + newer drugs bedaquiline/linezolid), has made already grim situation even more complicated. [4] Besides, adverse effects of prolonged treatment regimen, less effective and more toxic 2 nd line drugs, drug-drug interaction along with untreatable dormant or latent strains of Mtb further adds to the TB disease burden. [5,6] On top of it, COVID-19 has already reversed years of progress due to reduction in access to TB diagnostic and treatment options resulting in an increase in TB deaths (~1.3 million out of 9.9 affected in 2020) taking us back to the level of 2017.…”

Isoxazole carboxylic acid methyl ester-based urea and thiourea derivatives as promising antitubercular agents

“…Recent past has seen resurgence of tuberculosis (TB) drug research, ignited primarily by an urgent need to curtail TB epidemic as it continues to be the leading cause of death amongst infectious diseases globally, resulting in severe disruption in public health and socio-economic status. Increasing instances of drug resistance (DR), not only to existing drugs, but also to those in clinical pipeline pose a stiff challenge for drug development efforts, amidst concerning report from WHO stating years of progress being reversed by the ongoing coronavirus pandemic (COVID-19) [ 1 , 2 ]. Apart from disrupting essential TB services and assess to TB diagnosis and healthcare system, co-infection of TB and COVID-19, i.e., COVID-TB is emerging as a major threat to global TB burden and associated mortality [ 3 ].…”