Bedaquiline, Delamanid, Linezolid, and Clofazimine for Treatment of Pre-extensively Drug-Resistant Tuberculosis
Chandrasekaran Padmapriyadarsini, Vikram Vohra, Anuj Bhatnagar, Rajesh Solanki, Rathinam Sridhar, Lalitkumar Anande, M Muthuvijaylakshmi, Meera Bhatia Rana, Bharathi Jeyadeepa, Gaurav Taneja, S Balaji, Prashant Shah, N Saravanan, Vijay Chavan, Hemanth Kumar, Chinnayin Ponnuraja, Viktoriya Livchits, Monica Bahl, Umesh Alavadi, Kishmita Sachdeva, Soumya Swaminathan, for the BEAT India Team, Chandrasekaran Padmapriyadarsini, Bharathi Jeyadeepa, Lakshana, Nabila Akbar, Edwin Arulraj, Muthukumar, Muthukumar, Tamizharasan, S Balaji, Shri Vijay Bala Yogendra Shivakumar, M Muthuvijayalakshmi, Gayathri, C Ponnuraja, Hemanth Kumar, N Saravanan, Rajeswari Sridhar, Ramesh Kumar, Ramesh, Vikram Vohra, Meera Bhatia Rana, Neeta Singla, Vithal Prasad Myneedu, Ananiya Lawrence, Dipti Kushwaha, Deepak Kheraliya Shivam, Rohit Sarin, Anuj Bhatnagar, Gaurav Taneja, Alok Rawat, M Haniff, Rahul, Padma Rai, Savita Saini, Krishan Kumar Mathur, Rajesh Solanki, Pranav G Patel, Vaidehi Prajapati, Bhavesh Parmar, Kajal Wadkar, Prashant Shah, Snehal Parmar, Palak Vyas, Krupa Mistri, Lalitkumar Anade, Vijay Chavan, Namrata Kaur Bhui, Pranita Tipre, Daksha Shah, Surendra K Patwa, Anis Nhavakar, Audrey Brito, Kiran Keny, Vijaykumar Karanjkar, Kuntal Pal, Komal Godam, Madri Huje, Sanjana Ghadge, Madhuri Udmalle, Vivek Vijay Posture, Jaipal Bansode, Monica Bhal, Ranjan, Divya Pillai, Supriya Semwal, Shirali Labroo Viktoriya Livchits, Umesh Alavadi, Reuben Swamikan, Dorothy Nanzala Nasubo, Mallik Parmar, S. Sahu, YaDiul Mukadi, Soumya Swaminathan
Abstract
BACKGROUND: Treatment success rates for multidrug-resistant tuberculosis (MDR-TB) remain low globally. Availability of newer drugs has given scope to develop regimens that can be patient-friendly, less toxic, with improved outcomes. We proposed to determine the effectiveness of an entirely oral, short-course regimen with Bedaquiline and Delamanid in treating MDR-TB with additional resistance to fluoroquinolones (MDR-TBFQ+) or second-line injectable (MDR-TBSLI+). METHODS: We prospectively determined the effectiveness and safety of combining two new drugs with two repurposed drugs - Bedaquiline, Delamanid, Linezolid, and Clofazimine for 24-36 weeks in adults with pulmonary MDR-TBFQ+ or/and MDR-TBSLI+. The primary outcome was a favorable response at end of treatment, defined as two consecutive negative cultures taken four weeks apart. The unfavorable outcomes included bacteriologic or clinical failure during treatment period. RESULTS: Of the 165 participants enrolled, 158 had MDR-TBFQ+. At the end of treatment, after excluding 12 patients due to baseline drug susceptibility and culture negatives, 139 of 153 patients (91%) had a favorable outcome. Fourteen patients (9%) had unfavorable outcomes: four deaths, seven treatment changes, two bacteriological failures, and one withdrawal. During treatment, 85 patients (52%) developed myelosuppression, 69 (42%) reported peripheral neuropathy, and none had QTc(F) prolongation >500msec. At 48 weeks of follow-up, 131 patients showed sustained treatment success with the resolution of adverse events in the majority. CONCLUSION: After 24-36 weeks of treatment, this regimen resulted in a satisfactory favorable outcome in pulmonary MDR-TB patients with additional drug resistance. Cardiotoxicity was minimal, and myelosuppression, while common, was detected early and treated successfully.