Tuberculosis is one of the leading causes of death worldwide and the main cause of mortality from a single infectious agent. In 2019 alone, approximately 1.4 million people died, and 465,000 fell ill with drug-resistant TB (DR-TB), a complex form of TB that is costly and difficult to treat. Drug-resistant TB remains a significant threat to public health. In 2014 and 2015, all WHO Member States committed to ending the TB epidemic by adopting the WHO’s End TB strategy and the UN Sustainable Development Goals. However, today, the targets remain far from realized.
In 2012, after four decades without a new drug for treating TB, bedaquiline (BDQ) – a new bactericidal drug – received approval from the United States Food and Drug Administration (FDA) and was later included as part of WHO DR-TB treatment guidelines; this inclusion brought hope of achieving better clinical outcomes globally. In addition, bedaquiline has proven to be effective in treating resistant forms of TB in combination with other drugs.
According to the Global TB Report 2021, India leads the ranks of the global DR-TB Burden, with an estimated global burden of 27% of DR-TB cases and 34% of Global TB deaths. The National Tuberculosis Elimination Programme (NTEP) included the provision of bedaquiline in 2016 under a “conditional access programme” in pilot sites treating some of the patients with pre-XDR/XDR. Access to bedaquiline has subsequently been scaled up with the NTEP approving the use of bedaquiline for all pre-XDR/XDR patients for six months in 2019. Later, in 2021, extensions of bedaquiline beyond six months were included for exceptional cases with persistent positive cultures, although implementation of these extensions remain limited.
Despite the short time since the introduction of bedaquiline, cases of resistance have been reported worldwide, as well as worse clinical outcomes for patients with bedaquiline resistance. A systematic review of 13 studies, including data from India, found that 2.2% of patients acquired bedaquiline resistance (diagnosed by drug susceptibility testing) during treatment.  One study from South Africa found that bedaquiline resistance was associated with half the odds of treatment success compared to patients without bedaquiline resistance. 
The MSF DR-TB clinic in Mumbai offers free-of-cost diagnostics and treatment to patients withcomplex DR-TB who have failed or are suspected to be failing treatment. The MSF Mumbai project started witnessing bedaquiline resistance in previously exposed patients in 2019, and since 2022 MSF has been witnessing an increased number of people with bedaquiline resistance. The project’s data from December 2020 to August 2022 shows a proportion of resistance to bedaquiline of 25% (31/126). Although in a specialized cohort of patients, these numbers are extremely concerning. One of the main barriers to identifying bedaquiline resistance in India is the limited availability of bedaquiline drug sensitivity testing (DST) only available at two accredited Supra National Laboratories.
Conclusions and recommendations:
While MSF welcomes the scale-up of access to bedaquiline as one of the most effective drugs for treating patients with DR-TB, the emergence of resistance is an issue whichneeds urgent attention. The emerging resistance to bedaquiline underscores the need for effectiveindividualized treatment regimens for DR-TB patients, including increasing the access to bedaquiline and other drugs upfront and extending bedaquiline use beyond six months for all patients who require it.
Likewise, it is urgent to increase access to drug sensitivity testing (DST) for all patients exposed to the drug in order to be able to detect resistance.
MSF calls to donors, policymakers and programme implementers to:
- Allocate the necessary funding to improve access to individualized regimens upfront, avoiding interruptions. Use effective regimens, including the use of bedaquiline and delamanid for more than six months when needed.
- Increase access to bedaquiline drug sensitivity testing (DST), including it as routine for all patients previously exposed to the drug or failing a regimen containing bedaquiline.
- Strengthening surveillance and adherence in MDR-TB patients by using effective, simplified and non-toxic oral regimens.
- Enhancing policies, regulation and monitoring of second-line TB drugs to limit access by unregulated providers.
 According to the WHO classification: MDR TB: caused by an organism that is resistant to
at least isoniazid and rifampin. Pre-XDR TB: caused by an organism that is
resistant to isoniazid, rifampin, and a fluroquinolone OR by an organism that
is resistant to isoniazid, rifampin, and a second-line injectable (amikacin,
capreomycin, and kanamycin)
 Jahan Saeed Mallick, Parvati Nair,
Elizabeth Tabitha Abbew, Armand Van Deun, Tom Decroo, Acquired bedaquiline
resistance during the treatment of drug-resistant tuberculosis: a systematic
Resistance, Volume 4, Issue 2, April 2022, dlac029, https://doi.org/10.1093/jacamr/dlac029
 Assessment of epidemiological and genetic characteristics and clinical outcomes of resistance to Bedaquiline in patients treated for rifampicin-resistant tuberculosis: a cross-sectional and longitudinal study- Nazir Ahmed Ismail, Shaheed Vally Omar
4] National Institute for Research on Tuberculosis (NIRT), Chennai and National Institute for TB and Respiratory Disease (NITRD), Delhi- Public BDQ DST facilities still remain only 3 in the country