Swimming against the STREAM: Why STREAM 2 data cannot be easily applied to MDR-TB patients across India : Lung India

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Swimming against the STREAM: Why STREAM 2 data cannot be easily applied to MDR-TB patients across India

Udwadia, Zarir F.1; Patel, Jigneshkumar M.1; Batyala, Madhuri1; Tornheim, Jeffrey A.2; Rodrigues, Camilla3

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Lung India 40(3):p 290-291, May–Jun 2023. | DOI: 10.4103/lungindia.lungindia_74_23
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The STREAM Stage 2 study was a landmark, multicenter trial conducted across 13 sites in 7 countries. Enrolling more than 1000 participants over 8 years across two stages, STREAM is the world’s largest clinical platform for MDR-TB. STREAM Stage 2 assessed the efficacy of two bedaquiline-based shorter, standardized regimens for MDR-TB: a 9-month all-oral regimen and a 6-month regimen containing an injectable drug (kanamycin) for the first 2 months.[1] The primary outcome was met with both these regimens being not only non-inferior but in fact superior to the traditional longer treatment arms at 76 weeks of follow-up. The successful completion and publication of this major study in November 2022 were all the more creditable as it was conducted in the midst of a global pandemic and lockdowns.

Although India was a major recruiting center for the study, we have some reservations regarding the widespread programmatic adoption of either of these standardized regimens by the Indian National TB Elimination Program (NTEP).

Whilst India accounts for 1 of every 4 of the 450,000 MDR-TB cases encountered globally in 2021,[2] the majority of Indian MDR patients would not even qualify for either of the STREAM 2 regimens as fluoroquinolone (FQ) resistance is now so widely prevalent in India. At the specialized mycobacterial laboratory of our tertiary-care hospital, we have documented the relentless escalation in FQ-resistance rates in Mumbai from 3% in 1996 to 35% in 2004.[3] 68% of our current MDR-cohort have FQ-resistance on line probe assay (LPA), high-level D94G mutations in the majority.

We would also question the inclusion of high-dose isoniazid (Hh) as one of the core drugs in both the STREAM stage 2 regimens. Most Indian isoniazid-resistant strains carry katG mutations which confer high-grade resistance. Hh is unlikely to be effective in these patients according to a current WHO LPA manual.[4] LPA data from our mycobacterial laboratory showed that of the 9360 MDR-TB samples tested from January 2020 - October 2022, 85% carry katG mutations, thus effectively excluding the use of Hh in the majority of Indian patients.

With the specter of increasing bedaquiline resistance looming on the horizon,[5] we would urge that individualized regimens, chosen on the basis of phenotypic DST, must remain the standard of care in regions with high rates of complex drug resistance.[6]

Author contributions

All the authors contributed equally.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.


1. Goodall RL, Meredith SK, Nunn AJ, Bayissa A, Bhatnagar AK, Bronson G, et al. Evaluation of two short standardised regimens for the treatment of rifampicin-resistant tuberculosis (Stream Stage 2):An open-label, multicentre, randomised, non-inferiority trial. Lancet 2022;400:1858–68.
2. WHO. Global tuberculosis report 2022 Available from:https://www.who.int/teams/global-tuberculosis-programme/tb-reports/global-tuberculosis-report-2022.
3. Agrawal D, Udwadia ZF, Rodriguez C, Mehta A. Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in Mumbai, India. Int J Tuberc Lung Dis 2009;13:79–83.
4. Line probe assays for detection of drug-resistant tuberculosis:interpretation and reporting manual for laboratory staff and clinicians Geneva World Health Organization 2022 Licence:CC BY-NC-SA 3.0 IGO.
5. Kaniga K, Hasan R, Jou R, Vasiliauskienė E, Chuchottaworn C, Ismail N, et al. Bedaquiline drug resistance emergence assessment in multidrug-resistant tuberculosis (MDR-TB):A 5-year prospective in vitro surveillance study of Bedaquiline and other second-line drug susceptibility testing in MDR-TB isolates. J Clin Microbiol 2022;60:e0291920 doi:10.1128/JCM.02919-20.
6. Udwadia ZF, Tornheim JA, Ganatra S, DeLuca A, Rodrigues CS, Gupta A. Few eligible for the newly recommended short course MDR-TB regimen at a large Mumbai Private Clinic. BMC Infect Dis 2019;19:94.
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