The previous research results of the lab and Zhang Tianyu’s team from Guangdong-Hong Kong-Macau Joint Laboratory for Infectious Diseases (Biomedicine & Pharmacotherapy, 2019) confirms that the new anti-tuberculosis drug TB47 that targets the cytochrome bc1 oxidase complex of the respiratory chain of mycobacteria developed by the lab shows a unique combination of bactericidal and sterilizing activities together with clofazimine. The Bangladesh therapy with TB47 may shorten the course of treatment for tuberculosis of more than 9 months to less than 5 months, which is close to the 6-month course of treatment required for the current treatment of common tuberculosis with four first-line drugs. However, this therapy uses drug injection, while pure oral treatment is the current trend in the development of anti-tuberculosis drugs and new therapies. Oral treatment can not only reduce the pain of injections for patients, but also reduce patients’ chance to going out for medical treatment and improve their compliance. In addition, clinically, in the previous therapies contained pyrazinamide and quinolone drugs, it has been found that about half of MDR clinical strains of tuberculosis are resistant to these two drugs. Their specific role in the therapy is unclear.

This research shows that the combination of TB47 and the oral drug with expired patent is effective for the treatment of MDR-TB. TB47+clofazimine+linezolid is used as a fixed combination, and the use of linezolid should not exceed 3 months. This combination + pyrazinamide can achieve zero recurrence in no more than 4 months, that is, the combination may cure MDR-TB in no more than 4 months, even faster than the four first-line drugs for the treatment of common tuberculosis. The addition of levofloxacin to the combination did not significantly shorten the course of treatment. In addition, many clinical MDR-TB bacteria are resistant to quinolones and toxic to the nerves of patients (especially children). Therefore, if the therapy is successful in the future, there is no need to use quinolones to treat MDR-TB. It takes 5-6 months for pyrazinamide-free TB47+clofazimine+linezolid to complete cure the disease, which is basically the same with the use of four first-line drugs. In addition, it is very difficult to clinically detect the drug sensitivity of TB to pyrazinamide and MDR-TB is greatly resistant to pyrazinamide. Therefore, the three-drug combination is very promising for clinical practice and does not rely on drug sensitivity. Meanwhile, the research results also highlight the importance of rapid diagnosis of the clinical sensitivity of tuberculosis strains to pyrazinamide, because the combination of this drug and many other drugs has a synergistic effect that can shorten the course of treatment.

The research result was published online on Antimicrobial Agents and Chemotherapy, a journal of American Society for Microbiology on September 17. The first authors are Dr. Yu Wei and international master student Buhari Yusuf. The collaborators include Academician Zhong Nanshan of Guangzhou Medical University, Academician Gregory M. Cook of the University of Auckland and University of Otago, and Professor Dmitry A. Maslov of the Russian Academy of Sciences.