Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam
Background: The World health organization (WHO) recently recommended standardized all-oral shorter regimens for rifampicin resistant Tuberculosis (RR-TB). For highly resistant Tuberculosis patients such as pre-XDR-TB: RR-TB plus additional resistance to fluoroquinolones (FQ), the 6–9-months bedaquil...
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| Format: | Article |
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Frontiers Media S.A.
2022-10-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2022.1023704/full |
| _version_ | 1811339363941875712 |
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| author | Thi Mai Phuong Nguyen Binh Hoa Nguyen Thi Thanh Thuy Hoang Hoang Anh Nguyen Dinh Hoa Vu Mai Hoa Nguyen Bao Ngoc Nguyen Tom Decroo Viet Nhung Nguyen |
| author_facet | Thi Mai Phuong Nguyen Binh Hoa Nguyen Thi Thanh Thuy Hoang Hoang Anh Nguyen Dinh Hoa Vu Mai Hoa Nguyen Bao Ngoc Nguyen Tom Decroo Viet Nhung Nguyen |
| author_sort | Thi Mai Phuong Nguyen |
| collection | DOAJ |
| description | Background: The World health organization (WHO) recently recommended standardized all-oral shorter regimens for rifampicin resistant Tuberculosis (RR-TB). For highly resistant Tuberculosis patients such as pre-XDR-TB: RR-TB plus additional resistance to fluoroquinolones (FQ), the 6–9-months bedaquiline (bedaquiline)-based regimens or BDQ-based long regimens are recommended. The role of second-line injectable (SLI) drugs in the treatment of drug resistant TB is restricted because of safety concerns. Nevertheless, it is not well-known how all-oral long regimens (BDQ-long) perform compared to SLI-containing long regimens (BDQ/SLI-long) in terms of safety and effectiveness among patients with highly resistant TB.Method: A prospective observational cohort of patients with RR-TB additionally resistant to fluoroquinolones and/or second-line injectable, treated with either BDQ-long or BDQ/SLI-long regimens according to the guidance of the National Tuberculosis Program of Vietnam, enrolled between December 2015 and June 2017.Results: Of 99 patients enrolled, 42 (42%) patients were treated with BDQ-long and 57 (57%) with BDQ/SLI-long. More than 85% of patients were previously exposed to both FQ and SLI. FQ and SLI resistance were confirmed in 28 (67%) and 41 (98%) in the BDQ-long cohort and 48 (84%) and 17 (30%) in the BDQ/SLI-long cohort, respectively. Treatment success was achieved among 29 (69%) and 46 (81%) patients on the BDQ-long and BDQ/SLI-long regimen, respectively (p = 0.2). For both regimens, median time to first smear/culture sputum conversion was 2 months. All patients experienced at least one adverse event (AE) and 85% of them had at least one severe Adverse events. The median time to a first severe adverse event was 2 months. Among patients treated with BDQ-long a higher proportion of patients had three QT-prolonging drugs in the regimen (26.2% versus 7.0%; p = 0.009). The severe prolonged QTcF was observed in 22 (52.4%) and 22 (38.6%) patients on BDQ-long and BDQ/SLI-long, respectively. Overall, 30 (30%) patients had to either temporary or permanently discontinued or more TB drugs due to AEs.Conclusion: Treatment success was similar for both all-oral and SLI-containing BDQ-based long regimens in highly resistant TB patients. Both regimens had a similar high frequency of AEs. For both BDQ-long and BDQ/SLI-long regimens active AEs monitoring is essential. |
| first_indexed | 2024-04-13T18:25:29Z |
| format | Article |
| id | doaj.art-3f67da2310a34d6f89e1bb78d6074faf |
| institution | Directory Open Access Journal |
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| language | English |
| last_indexed | 2024-04-13T18:25:29Z |
| publishDate | 2022-10-01 |
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| spelling | doaj.art-3f67da2310a34d6f89e1bb78d6074faf2022-12-22T02:35:15ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122022-10-011310.3389/fphar.2022.10237041023704Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in VietnamThi Mai Phuong Nguyen0Binh Hoa Nguyen1Thi Thanh Thuy Hoang2Hoang Anh Nguyen3Dinh Hoa Vu4Mai Hoa Nguyen5Bao Ngoc Nguyen6Tom Decroo7Viet Nhung Nguyen8Vietnam National Lung Hospital, Hanoi, VietnamVietnam National Lung Hospital, Hanoi, VietnamVietnam National Lung Hospital, Hanoi, VietnamNational Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacy, Hanoi, VietnamNational Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacy, Hanoi, VietnamNational Drug Information and Adverse Drug Reaction Monitoring Centre, Hanoi University of Pharmacy, Hanoi, VietnamSchool of Pharmacy, Memorial University of Newfoundland, John’s, NL, CanadaInstitute of Tropical Medicine Antwerp, Antwerp, BelgiumVietnam National Lung Hospital, Hanoi, VietnamBackground: The World health organization (WHO) recently recommended standardized all-oral shorter regimens for rifampicin resistant Tuberculosis (RR-TB). For highly resistant Tuberculosis patients such as pre-XDR-TB: RR-TB plus additional resistance to fluoroquinolones (FQ), the 6–9-months bedaquiline (bedaquiline)-based regimens or BDQ-based long regimens are recommended. The role of second-line injectable (SLI) drugs in the treatment of drug resistant TB is restricted because of safety concerns. Nevertheless, it is not well-known how all-oral long regimens (BDQ-long) perform compared to SLI-containing long regimens (BDQ/SLI-long) in terms of safety and effectiveness among patients with highly resistant TB.Method: A prospective observational cohort of patients with RR-TB additionally resistant to fluoroquinolones and/or second-line injectable, treated with either BDQ-long or BDQ/SLI-long regimens according to the guidance of the National Tuberculosis Program of Vietnam, enrolled between December 2015 and June 2017.Results: Of 99 patients enrolled, 42 (42%) patients were treated with BDQ-long and 57 (57%) with BDQ/SLI-long. More than 85% of patients were previously exposed to both FQ and SLI. FQ and SLI resistance were confirmed in 28 (67%) and 41 (98%) in the BDQ-long cohort and 48 (84%) and 17 (30%) in the BDQ/SLI-long cohort, respectively. Treatment success was achieved among 29 (69%) and 46 (81%) patients on the BDQ-long and BDQ/SLI-long regimen, respectively (p = 0.2). For both regimens, median time to first smear/culture sputum conversion was 2 months. All patients experienced at least one adverse event (AE) and 85% of them had at least one severe Adverse events. The median time to a first severe adverse event was 2 months. Among patients treated with BDQ-long a higher proportion of patients had three QT-prolonging drugs in the regimen (26.2% versus 7.0%; p = 0.009). The severe prolonged QTcF was observed in 22 (52.4%) and 22 (38.6%) patients on BDQ-long and BDQ/SLI-long, respectively. Overall, 30 (30%) patients had to either temporary or permanently discontinued or more TB drugs due to AEs.Conclusion: Treatment success was similar for both all-oral and SLI-containing BDQ-based long regimens in highly resistant TB patients. Both regimens had a similar high frequency of AEs. For both BDQ-long and BDQ/SLI-long regimens active AEs monitoring is essential.https://www.frontiersin.org/articles/10.3389/fphar.2022.1023704/fullpre-XDR TB treatmentall oral regimeninjectable secondline drugQT prolongationbedaquline |
| spellingShingle | Thi Mai Phuong Nguyen Binh Hoa Nguyen Thi Thanh Thuy Hoang Hoang Anh Nguyen Dinh Hoa Vu Mai Hoa Nguyen Bao Ngoc Nguyen Tom Decroo Viet Nhung Nguyen Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam Frontiers in Pharmacology pre-XDR TB treatment all oral regimen injectable secondline drug QT prolongation bedaquline |
| title | Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam |
| title_full | Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam |
| title_fullStr | Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam |
| title_full_unstemmed | Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam |
| title_short | Safety and effectiveness of all-oral and injectable-containing, bedaquiline-based long treatment regimen for pre-XDR tuberculosis in Vietnam |
| title_sort | safety and effectiveness of all oral and injectable containing bedaquiline based long treatment regimen for pre xdr tuberculosis in vietnam |
| topic | pre-XDR TB treatment all oral regimen injectable secondline drug QT prolongation bedaquline |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2022.1023704/full |
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