Recent Advancement of Tubercular Therapy in MDR-TB and DR-TB

Abstract

Despite international efforts to control and eradicate tuberculosis (TB), it continues to be a major cause of morbidity and mortality on a global scale. Drug-resistant TB (DRTB) is a serious public health threat that affects global health security, economic burden, and access to high-quality care. To effectively address this issue, cooperation between governments, international organizations, and healthcare systems is essential. In December 2012, the Food and Drug Administration (FDA) granted accelerated approval for bedaquiline (BDQ), a diarylquinoline drug, based on analysis of time to sputum culture conversion from two phase 2 trials.Although drug resistance is an inevitable side effect of drug use, multi-drug resistance can be controlled with precise diagnosis and customized treatment plans.Mycobacterium in MDR-TB is resistant to frontline medications such as isoniazid and rifampicin. Over 50% of medications are now resistant, making identification and treatment a pressing worldwide concern.More than any other infectious disease, tuberculosis (TB) ranks as the ninth leading cause of mortality worldwide. Due to increasing drug resistance, the epidemic is still present and will need substantial attention and funding to be eradicated. Despite the relatively low number of resources committed, several significant advancements have recently been made through increased collaboration and research networks. Drug-resistant TB regimens are increasingly using the newly available medications bedaquiline and delamanid as well as the repurposed medications linezolid, clofazimine, and carbapenems.In addition to appropriate use and drug resistance monitoring, combination therapy with additional anti-TB medications is recommended to prevent resistance. Following positive results from a phase III trial, the US FDA approved Pretomanid in August 2019. Pretomanid, linezolid, bedaquiline, A part of the BPaLM regimen, and moxifloxacin, has been authorized for the treatment of individuals with treatment-intolerant or non-responsive MDRTB or extensive pulmonary DRTB. Patients with MDRTB now have better clinical results and a higher quality of life because to this important management breakthrough. The WHO guidelines\' inclusion is positive for the worldwide fight against DRTB. New therapeutic targets within the TB pathogenesis have been found and studied by researchers, providing encouraging opportunities for the creation of novel anti-TB medications.

Introduction

Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide despite being preventable and treatable. In 2018, only a fraction of the estimated half a million rifampicin-resistant TB (RR-TB) cases were diagnosed and treated properly, with treatment success rates stagnating around 56%. MDR-TB, resistant to both rifampicin and isoniazid, poses a major global health challenge, worsened by factors like HIV co-infection, poor case detection, treatment noncompliance, overcrowding, and migration.

Traditional TB treatment involves a six-month multi-drug regimen effective for drug-sensitive TB but less so for drug-resistant strains, which require longer, more toxic, and complex treatments with lower success rates. Newer drugs like bedaquiline and delamanid show promise for improving outcomes in MDR/RR-TB cases.

Drug resistance in TB arises from genetic mutations in Mycobacterium tuberculosis (Mtb), often driven by incomplete or irregular treatment and facilitated by transmission in crowded settings. Resistance mechanisms include enzymatic drug inactivation, target modification, efflux pumps, and other adaptive changes. MDR-TB is spreading globally, especially in countries like India, China, and Russia, mainly due to inadequate treatment regimens and healthcare system challenges.

Understanding TB resistance involves both microbial genetics and host/environmental factors influencing mutation rates and drug tolerance. Addressing MDR-TB requires updated treatment protocols, better diagnostics, patient adherence, and global health efforts to contain its spread.

Conclusion

MDRTB poses a threat to TB eradication and a significant barrier to TB control worldwide. Better handling of vulnerable TB cases, as well as the detection and management of the majority of MDRTB patients are necessary to keep this epidemic under control. Improvements in the treatment of DRTB have led to shorter MDRTB regimens and the availability of new or repurposed drugs including BDQ DLM, clofazimine, and linezolid. For all TB patients, including those who are both sensitive and resistant to current treatments, the goal is to develop a universal new regimen. Reducing complications and maintaining high cure rates require a shorter duration of treatment. The global TB community, which includes funders and legislators, must work together to ensure that patients who require these drugs can have them.

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Copyright © 2025 Fiza Patel(Main Author), Sushant Benade, Shraddha Nerkar, Priyanka Gavhade , Sheetal Rode, Dr. Ashoke Giri. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.