Tackling Drug-Resistant Tuberculosis: New Challenges from the Old Pathogen Mycobacterium tuberculosis

Abstract

Antibiotics have played a crucial role in the reduction in the incidence of TB globally as evidenced by the fact that before the mid-20th century, the mortality rate within five years of the onset of the disease was 50%. The use of antibiotics has eliminated TB as a devastating disease, but the challenge of resistance to anti-TB drugs, which had already been described at the time of the introduction of streptomycin, has become a major global issue in disease management. Mismanagement of multidrug-resistant tuberculosis (MDR-TB) cases, resulting from intermittent drug use, prescription errors, and non-compliance of patients, has been identified as a critical risk factor for the development of extensively drug-resistant tuberculosis (XDR-TB). Antimicrobial resistance (AMR) in TB is a multi-factorial, complex problem of microbes evolving to escape antibiotics, the gradual decline in antibiotic development, and different economic and social conditions. In this review, we summarize recent advances in our understanding of how Mycobacterium tuberculosis evolves drug resistance. We also highlight the importance of developing shorter regimens that rapidly reach bacteria in diverse host environments, eradicating all mycobacterial populations and preventing the evolution of drug resistance. Lastly, we also emphasize that the current burden of this ancient disease is driven by a combination of complex interactions between mycobacterial and host factors, and that only a holistic approach that effectively addresses all the critical issues associated with drug resistance will limit the further spread of drug-resistant strains throughout the community.

Breaking barriers: The potential of nanosystems in antituberculosis therapy

“…In 2020, 69 % of new TB cases worldwide were MDR, and 80 % of previously treated cases tested positive for MDR [ 15 ]. As with other microorganisms, the evolution of resistant TB is recognized as a natural biological event, resulting from a multifactorial scenario, infused by genetic alterations, poor clinical management, prolonged use of antimicrobial drugs, or poor adherence to TB treatment [ 16 , 17 ]. However, resistant strains require second-line drugs like aminoglycosides, polypeptides, fluoroquinolones, amikacin, kanamycin, thioamides, cycloserine, p-aminosalicylic acid and others, which present problems related to higher cost, greater toxicity, and greater side effects compared to first-line drugs [ 14 , 18 , 19 ].…”

The Antitubercular Activities of Natural Products with Fused-Nitrogen-Containing Heterocycles

“…The success of novel treatment regimens will be determined by the rate at which resistance will emerge to these drugs. Mtb has successfully developed resistance to all clinically available antitubercular drugs in vitro and in vivo [ 3 , 4 ], thus new agents will be needed to combat the inevitable global spread of such resistant strains.…”

Current development of therapeutic vaccines for the treatment of chronic infectious diseases

“…Chronic infectious diseases are often difficult to cure with a single treatment due to the nature of the causative pathogen continuously exists in the body, and long-term treatment may lead to the development of mutant strains resistant to the treatment. In fact, there are reports of the occurrence of multidrug-resistant pathogens in many chronic infectious diseases [ 2 3 4 ], which suggests the limitations of drug therapy in the treatment of chronic infectious diseases.…”