S Oelofse1, A Esmail1, A H Diacon2, F Conradie3, O Olayanju1, N Ngubane4, P Howell3, D Everitt5, A M Crook6, C M Mendel5, G H Wills6, M Olugbosi7, A Del Parigi5, E Sun5, A Calatroni8, M Spigelman5, K Dheda9. 1. Centre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town (UCT), Cape Town, South Africa. 2. Task Applied Science and Stellenbosch University, Cape Town, South Africa. 3. Clinical HIV Research Unit, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa, Sizwe Tropical Disease Hospital, Sandringham, South Africa. 4. Task Applied Science and Stellenbosch University, Cape Town, South Africa, King DinuZulu Hospital Complex, Durban, South Africa. 5. TB Alliance, New York, NY, USA. 6. Institute of Clinical Trials and Methodology, University College London, London, UK. 7. TB Alliance, Pretoria, South Africa. 8. Rho Federal Systems Division, Inc., Durham, NC, USA. 9. Centre for Lung Infection and Immunity, Division of Pulmonology and UCT Lung Institute, Department of Medicine, University of Cape Town (UCT), Cape Town, South Africa, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, UK.
Abstract
BACKGROUND: There are no data comparing the 6-9 month oral three-drug Nix regimen (bedaquiline, pretomanid and linezolid [BPaL]) to conventional regimens containing bedaquiline (B, BDQ) and linezolid (L, LZD). METHODS: Six-month post end-of-treatment outcomes were compared between Nix-TB (n = 109) and 102 prospectively recruited extensively drug-resistant TB patients who received an ˜18-month BDQ-based regimen (median of 8 drugs). A subset of patients received BDQ and LZD (n = 86), and a subgroup of these (n = 75) served as individually matched controls in a pairwise comparison to determine differences in regimen efficacy. RESULTS: Favourable outcomes (%) were significantly better with BPaL than with the B-L-based combination regimen (98/109, 89.9% vs. 56/86, 65.1%; adjusted relative risk ratio [aRRR] 1.35; P < 0.001) and in the matched pairwise analysis (67/75, 89.3% vs. 48/75, 64.0%; aRRR 1.39; P = 0.001), despite significantly higher baseline bacterial load and prior second-line drug exposure in the BPaL cohort. Time to culture conversion (P < 0.001), time to unfavourable outcome (P < 0.01) and time to death (P < 0.03) were significantly better or lower with BPaL than the B-L-based combinations. CONCLUSION: The BPaL regimen (and hence substitution of multiple other drugs by pretomanid and/or higher starting-dose LZD) may improve outcomes in drug-resistant TB patients with poor prognostic features. However, prospective controlled studies are required to definitively answer this question.
BACKGROUND: There are no data comparing the 6-9 month oral three-drug Nix regimen (bedaquiline, pretomanid and linezolid [BPaL]) to conventional regimens containing bedaquiline (B, BDQ) and linezolid (L, LZD). METHODS: Six-month post end-of-treatment outcomes were compared between Nix-TB (n = 109) and 102 prospectively recruited extensively drug-resistant TBpatients who received an ˜18-month BDQ-based regimen (median of 8 drugs). A subset of patients received BDQ and LZD (n = 86), and a subgroup of these (n = 75) served as individually matched controls in a pairwise comparison to determine differences in regimen efficacy. RESULTS: Favourable outcomes (%) were significantly better with BPaL than with the B-L-based combination regimen (98/109, 89.9% vs. 56/86, 65.1%; adjusted relative risk ratio [aRRR] 1.35; P < 0.001) and in the matched pairwise analysis (67/75, 89.3% vs. 48/75, 64.0%; aRRR 1.39; P = 0.001), despite significantly higher baseline bacterial load and prior second-line drug exposure in the BPaL cohort. Time to culture conversion (P < 0.001), time to unfavourable outcome (P < 0.01) and time to death (P < 0.03) were significantly better or lower with BPaL than the B-L-based combinations. CONCLUSION: The BPaL regimen (and hence substitution of multiple other drugs by pretomanid and/or higher starting-dose LZD) may improve outcomes in drug-resistant TBpatients with poor prognostic features. However, prospective controlled studies are required to definitively answer this question.
Authors: Sara Occhineri; Tommaso Matucci; Laura Rindi; Giusy Tiseo; Marco Falcone; Niccolò Riccardi; Giorgio Besozzi Journal: Curr Res Pharmacol Drug Discov Date: 2022-09-09