Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study
Abstract Background Bedaquiline (BDQ) is a core drug for rifampicin-resistant tuberculosis (RR-TB) treatment. Accurate prediction of a BDQ-resistant phenotype from genomic data is not yet possible. A Bayesian method to predict BDQ resistance probability from next-generation sequencing data has been...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2022-11-01
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| Series: | BMC Infectious Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12879-022-07865-7 |
| _version_ | 1811210881806106624 |
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| author | Pham Hien Trang Tu Degefaye Zelalem Anlay Anzaan Dippenaar Emilyn Costa Conceição Jasna Loos Annelies Van Rie |
| author_facet | Pham Hien Trang Tu Degefaye Zelalem Anlay Anzaan Dippenaar Emilyn Costa Conceição Jasna Loos Annelies Van Rie |
| author_sort | Pham Hien Trang Tu |
| collection | DOAJ |
| description | Abstract Background Bedaquiline (BDQ) is a core drug for rifampicin-resistant tuberculosis (RR-TB) treatment. Accurate prediction of a BDQ-resistant phenotype from genomic data is not yet possible. A Bayesian method to predict BDQ resistance probability from next-generation sequencing data has been proposed as an alternative. Methods We performed a qualitative study to investigate the decision-making of physicians when facing different levels of BDQ resistance probability. Fourteen semi-structured interviews were conducted with physicians experienced in treating RR-TB, sampled purposefully from eight countries with varying income levels and burden of RR-TB. Five simulated patient scenarios were used as a trigger for discussion. Factors influencing the decision of physicians to prescribe BDQ at macro-, meso- and micro levels were explored using thematic analysis. Results The perception and interpretation of BDQ resistance probability values varied widely between physicians. The limited availability of other RR-TB drugs and the high cost of BDQ hindered physicians from altering the BDQ-containing regimen and incorporating BDQ resistance probability in their decision-making. The little experience with BDQ susceptibility testing and whole-genome sequencing results, and the discordance between phenotypic susceptibility and resistance probability were other barriers for physicians to interpret the resistance probability estimates. Especially for BDQ resistance probabilities between 25% and 70%, physicians interpreted the resistance probability value dynamically, and other factors such as clinical and bacteriological treatment response, history of exposure to BDQ, and resistance profile were often considered more important than the BDQ probability value for the decision to continue or stop BDQ. In this grey zone, some physicians opted to continue BDQ but added other drugs to strengthen the regimen. Conclusions This study highlights the complexity of physicians' decision-making regarding the use of BDQ in RR-TB regimens for different levels of BDQ resistance probability.. Ensuring sufficient access to BDQ and companion drugs, improving knowledge of the genotype–phenotype association for BDQ resistance, availability of a rapid molecular test, building next-generation sequencing capacity, and developing a clinical decision support system incorporating BDQ resistance probability will all be essential to facilitate the implementation of BDQ resistance probability in personalizing treatment for patients with RR-TB. |
| first_indexed | 2024-04-12T05:02:11Z |
| format | Article |
| id | doaj.art-13bff74b96504de396da7ada8ae260be |
| institution | Directory Open Access Journal |
| issn | 1471-2334 |
| language | English |
| last_indexed | 2024-04-12T05:02:11Z |
| publishDate | 2022-11-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Infectious Diseases |
| spelling | doaj.art-13bff74b96504de396da7ada8ae260be2022-12-22T03:46:57ZengBMCBMC Infectious Diseases1471-23342022-11-0122111210.1186/s12879-022-07865-7Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative studyPham Hien Trang Tu0Degefaye Zelalem Anlay1Anzaan Dippenaar2Emilyn Costa Conceição3Jasna Loos4Annelies Van Rie5Department of Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of AntwerpDepartment of Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of AntwerpDepartment of Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of AntwerpDepartment of Science and Innovation, National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, South African Medical Research Council Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch UniversityDean’s Office, Faculty of Medicine and Health Sciences, University of AntwerpDepartment of Family Medicine and Population Health, Faculty of Medicine and Health Sciences, University of AntwerpAbstract Background Bedaquiline (BDQ) is a core drug for rifampicin-resistant tuberculosis (RR-TB) treatment. Accurate prediction of a BDQ-resistant phenotype from genomic data is not yet possible. A Bayesian method to predict BDQ resistance probability from next-generation sequencing data has been proposed as an alternative. Methods We performed a qualitative study to investigate the decision-making of physicians when facing different levels of BDQ resistance probability. Fourteen semi-structured interviews were conducted with physicians experienced in treating RR-TB, sampled purposefully from eight countries with varying income levels and burden of RR-TB. Five simulated patient scenarios were used as a trigger for discussion. Factors influencing the decision of physicians to prescribe BDQ at macro-, meso- and micro levels were explored using thematic analysis. Results The perception and interpretation of BDQ resistance probability values varied widely between physicians. The limited availability of other RR-TB drugs and the high cost of BDQ hindered physicians from altering the BDQ-containing regimen and incorporating BDQ resistance probability in their decision-making. The little experience with BDQ susceptibility testing and whole-genome sequencing results, and the discordance between phenotypic susceptibility and resistance probability were other barriers for physicians to interpret the resistance probability estimates. Especially for BDQ resistance probabilities between 25% and 70%, physicians interpreted the resistance probability value dynamically, and other factors such as clinical and bacteriological treatment response, history of exposure to BDQ, and resistance profile were often considered more important than the BDQ probability value for the decision to continue or stop BDQ. In this grey zone, some physicians opted to continue BDQ but added other drugs to strengthen the regimen. Conclusions This study highlights the complexity of physicians' decision-making regarding the use of BDQ in RR-TB regimens for different levels of BDQ resistance probability.. Ensuring sufficient access to BDQ and companion drugs, improving knowledge of the genotype–phenotype association for BDQ resistance, availability of a rapid molecular test, building next-generation sequencing capacity, and developing a clinical decision support system incorporating BDQ resistance probability will all be essential to facilitate the implementation of BDQ resistance probability in personalizing treatment for patients with RR-TB.https://doi.org/10.1186/s12879-022-07865-7Rifampicin-resistant tuberculosisBedaqulineResistance probabilityTreatment decision |
| spellingShingle | Pham Hien Trang Tu Degefaye Zelalem Anlay Anzaan Dippenaar Emilyn Costa Conceição Jasna Loos Annelies Van Rie Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study BMC Infectious Diseases Rifampicin-resistant tuberculosis Bedaquline Resistance probability Treatment decision |
| title | Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study |
| title_full | Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study |
| title_fullStr | Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study |
| title_full_unstemmed | Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study |
| title_short | Bedaquiline resistance probability to guide treatment decision making for rifampicin-resistant tuberculosis: insights from a qualitative study |
| title_sort | bedaquiline resistance probability to guide treatment decision making for rifampicin resistant tuberculosis insights from a qualitative study |
| topic | Rifampicin-resistant tuberculosis Bedaquline Resistance probability Treatment decision |
| url | https://doi.org/10.1186/s12879-022-07865-7 |
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