Multidrug-resistant TB
Multidrug-resistant tuberculosis (MDR-TB) is a form of tuberculosis caused by Mycobacterium tuberculosis strains resistant to at least isoniazid and rifampicin. Each year, MDR-TB affects half a million people globally, with a treatment success of approximately 60%, which is worse in people living with HIV. Despite significant advancements in treatment regimens, there are several gaps including lack of diagnostics, biomarkers and challenging access and drug supply lines. A large proportion of survivors endure long-term health complications, largely due to the extensive disease duration and the toxicity of second-line treatment options. Lately bedaquiline resistance has been reported threatening advancements made thus far.
The long-term complications associated with MDR-TB can include severe respiratory issues, persistent fatigue, and a decreased quality of life, impacting the individual's ability to return to normal daily activities.
Current research is aimed at bridging the diagnostic gap, identifying predictive factors for treatment outcomes, working on shorter simpler safer regimens, host directed therapies and managing hard-to-treat disease including bedaquiline resistance. Research also involves evaluation of effectiveness, tolerability, toxicity and resistance to new and repurposed drugs when introduced into drug-resistant TB treatment programmes. Additional research in Indonesia is evaluating implementation of targeted next-generation sequencing directly on sputum for diagnosis of MDR-TB, and characterising links between diabetes and antimicrobial resistance.
Outputs
- Tiberi S, Payen MC, Sotgiu G, D'Ambrosio L, Alarcon Guizado V, Alffenaar JW, Abdo Arbex M, Caminero JA, Centis R, De Lorenzo S, Gaga M, Gualano G, Roby Arias AJ, Scardigli A, Skrahina A, Solovic I, Sulis G, Tadolini M, Akkerman OW, Alarcon Arrascue E, Aleska A, Avchinko V, Bonini EH, Chong Marín FA, Collahuazo López L, de Vries G, Dore S, Kunst H, Matteelli A, Moschos C, Palmieri F, Papavasileiou A, Spanevello A, Vargas Vasquez D, Viggiani P, White V, Zumla A, Migliori GB. Effectiveness and safety of meropenem/clavulanate-containing regimens in the treatment of MDR- and XDR-TB. Eur Respir J. 2016 Apr;47(4):1235-43. doi: 10.1183/13993003.02146-2015. Epub 2016 Mar 10. PMID: 26965290.
- Tiberi S, Pontali E, Tadolini M, D'Ambrosio L, Migliori GB. Challenging MDR-TB clinical problems - The case for a new Global TB Consilium supporting the compassionate use of new anti-TB drugs. Int J Infect Dis. 2019 Mar;80S:S68-S72. doi: 10.1016/j.ijid.2019.01.040. Epub 2019 Jan 25. PMID: 30690212.
- Diacon AH, Barry CE 3rd, Carlton A, Chen RY, Davies M, de Jager V, Fletcher K, Koh GCKW, Kontsevaya I, Heyckendorf J, Lange C, Reimann M, Penman SL, Scott R, Maher-Edwards G, Tiberi S, Vlasakakis G, Upton CM, Aguirre DB. A first-in-class leucyl-tRNA synthetase inhibitor, ganfeborole, for rifampicin-susceptible tuberculosis: a phase 2a open-label, randomized trial. Nat Med. 2024 Mar;30(3):896-904. doi: 10.1038/s41591-024-02829-7. Epub 2024 Feb 16. PMID: 38365949; PMCID: PMC10957473.
- Brust JCM, Gandhi NR, Wasserman S, Maartens G, Omar SV, Ismail NA, Campbell A, Joseph L, Hahn A, Allana S, Hernandez-Romieu AC, Zhang C, Mlisana K, Viljoen CA, Zalta B, Ebrahim I, Franczek M, Master I, Ramangoaela L, Te Riele J, Meintjes G. Effectiveness and Cardiac Safety of Bedaquiline-Based Therapy for Drug-Resistant Tuberculosis: A Prospective Cohort Study. Clin Infect Dis. 2021;73(11):2083-2092.
- Wasserman S, Louw G, Ramangoaela L, Barber G, Hayes C, Omar SV, Maartens G, Barry C, Song T, Meintjes G. Linezolid resistance in patients with drug-resistant TB and treatment failure in South Africa. J Antimicrob Chemother. 2019 Aug 1;74(8):2377-2384.
Projects
EX-DR TB