Impact of heteroresistance on treatment outcomes of people with drug-resistant TB
BACKGROUND: Poor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown. MET...
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International Union Against Tuberculosis and Lung Disease (The Union)
2024-10-01
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| author | R. Crowder M. Kato-Maeda B. Schwem A. dela Tonga D.M. Geocaniga-Gaviola E. Lopez C.L. Valdez A.R. Lim N. Hunat A.G. Sedusta C.A. Sacopon G.A.M. Atienza E. Bulag D. Lim J. Bascuña K. Shah R.P. Basillio C.A. Berger M.C.D.P. Lopez S. Sen C. Allender M. Folkerts U. Karaoz E. Brodie S. Mitarai A.M.C. Garfin M.C. Ama D.M. Engelthaler A. Cattamanchi R. Destura |
| author_facet | R. Crowder M. Kato-Maeda B. Schwem A. dela Tonga D.M. Geocaniga-Gaviola E. Lopez C.L. Valdez A.R. Lim N. Hunat A.G. Sedusta C.A. Sacopon G.A.M. Atienza E. Bulag D. Lim J. Bascuña K. Shah R.P. Basillio C.A. Berger M.C.D.P. Lopez S. Sen C. Allender M. Folkerts U. Karaoz E. Brodie S. Mitarai A.M.C. Garfin M.C. Ama D.M. Engelthaler A. Cattamanchi R. Destura |
| author_sort | R. Crowder |
| collection | DOAJ |
| description | BACKGROUND: Poor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown. METHODS: We used targeted deep sequencing to identify mutations associated with DR-TB and heteroresistance in culture samples of 624 people with DR-TB. We evaluated the association between heteroresistance and time to unfavorable treatment outcome using Cox proportional hazards regression. RESULTS: The proportion of drug-resistant isolates with a known mutation conferring resistance was lower for streptomycin (45.2%) and second-line injectables (79.1%) than for fluoroquinolones (86.7%), isoniazid (93.2%) and rifampin (96.5%). Fifty-two (8.3%) had heteroresistance, and it was more common for fluoroquinolones (4.6%) than rifampin (2.2%), second-line injectables (1.4%), streptomycin (1.7%), or isoniazid (1.3%). There was no association between heteroresistance and time to unfavorable outcome among people with multidrug-resistant TB (adjusted hazard ratio [aHR] 1.74, 95% CI 0.39–7.72) or pre-extensively DR-TB (aHR 0.65, 95% CI 0.24–1.72). CONCLUSIONS: Heteroresistance was relatively common (8.3%) among people with DR-TB in the Philippines. However, we found insufficient evidence to demonstrate an impact on unfavorable treatment outcomes. |
| format | Article |
| id | doaj-art-45e46d6976b24385948ce2fce25ff42b |
| institution | Kabale University |
| issn | 3005-7590 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | International Union Against Tuberculosis and Lung Disease (The Union) |
| record_format | Article |
| series | IJTLD Open |
| spelling | doaj-art-45e46d6976b24385948ce2fce25ff42b2025-01-23T13:28:38ZengInternational Union Against Tuberculosis and Lung Disease (The Union)IJTLD Open3005-75902024-10-0111046647210.5588/ijtldopen.24.03437Impact of heteroresistance on treatment outcomes of people with drug-resistant TBR. Crowder0M. Kato-Maeda1B. Schwem2A. dela Tonga3D.M. Geocaniga-Gaviola4E. Lopez5C.L. Valdez6A.R. Lim7N. Hunat8A.G. Sedusta9C.A. Sacopon10G.A.M. Atienza11E. Bulag12D. Lim13J. Bascuña14K. Shah15R.P. Basillio16C.A. Berger17M.C.D.P. Lopez18S. Sen19C. Allender20M. Folkerts21U. Karaoz22E. Brodie23S. Mitarai24A.M.C. Garfin25M.C. Ama26D.M. Engelthaler27A. Cattamanchi28R. Destura29Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA;Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA;University of the Philippines, National Institutes of Health, Manila, Philippines;University of the Philippines, National Institutes of Health, Manila, Philippines;Philippines Department of Health, Manila, Philippines;Philippines Department of Health, Manila, Philippines;Philippines Department of Health, Manila, Philippines;Philippines Department of Health, Manila, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA;University of the Philippines, National Institutes of Health, Manila, Philippines;Department of Preventive Medicine, University of Tennessee Health Science Center, Memphis, TN, USA;Pathogen and Microbiome Division, Translational Genomics Research Institute, Flagstaff, AZ, USA;Pathogen and Microbiome Division, Translational Genomics Research Institute, Flagstaff, AZ, USA;Ecology Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA;Ecology Department, Lawrence Berkeley National Laboratory, Berkeley, CA, USA;Research Institute for Tuberculosis, Tokyo, Japan;Philippines Department of Health, Manila, Philippines;National Tuberculosis Reference Laboratory, Research Institute for Tropical Medicine, Muntinlupa, Philippines;Pathogen and Microbiome Division, Translational Genomics Research Institute, Flagstaff, AZ, USA;Division of Pulmonary and Critical Care Medicine, San Francisco General Hospital, University of California San Francisco, San Francisco, CA, USA;University of the Philippines, National Institutes of Health, Manila, Philippines;BACKGROUND: Poor treatment outcomes among people with drug-resistant TB (DR-TB) are a major concern. Heteroresistance (presence of susceptible and resistant Mycobacterium tuberculosis in the same sample) has been identified in some people with TB, but its impact on treatment outcomes is unknown. METHODS: We used targeted deep sequencing to identify mutations associated with DR-TB and heteroresistance in culture samples of 624 people with DR-TB. We evaluated the association between heteroresistance and time to unfavorable treatment outcome using Cox proportional hazards regression. RESULTS: The proportion of drug-resistant isolates with a known mutation conferring resistance was lower for streptomycin (45.2%) and second-line injectables (79.1%) than for fluoroquinolones (86.7%), isoniazid (93.2%) and rifampin (96.5%). Fifty-two (8.3%) had heteroresistance, and it was more common for fluoroquinolones (4.6%) than rifampin (2.2%), second-line injectables (1.4%), streptomycin (1.7%), or isoniazid (1.3%). There was no association between heteroresistance and time to unfavorable outcome among people with multidrug-resistant TB (adjusted hazard ratio [aHR] 1.74, 95% CI 0.39–7.72) or pre-extensively DR-TB (aHR 0.65, 95% CI 0.24–1.72). CONCLUSIONS: Heteroresistance was relatively common (8.3%) among people with DR-TB in the Philippines. However, we found insufficient evidence to demonstrate an impact on unfavorable treatment outcomes.https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000010/art00007drug resistance-associated mutationsdr-tbtuberculosis |
| spellingShingle | R. Crowder M. Kato-Maeda B. Schwem A. dela Tonga D.M. Geocaniga-Gaviola E. Lopez C.L. Valdez A.R. Lim N. Hunat A.G. Sedusta C.A. Sacopon G.A.M. Atienza E. Bulag D. Lim J. Bascuña K. Shah R.P. Basillio C.A. Berger M.C.D.P. Lopez S. Sen C. Allender M. Folkerts U. Karaoz E. Brodie S. Mitarai A.M.C. Garfin M.C. Ama D.M. Engelthaler A. Cattamanchi R. Destura Impact of heteroresistance on treatment outcomes of people with drug-resistant TB IJTLD Open drug resistance-associated mutations dr-tb tuberculosis |
| title | Impact of heteroresistance on treatment outcomes of people with drug-resistant TB |
| title_full | Impact of heteroresistance on treatment outcomes of people with drug-resistant TB |
| title_fullStr | Impact of heteroresistance on treatment outcomes of people with drug-resistant TB |
| title_full_unstemmed | Impact of heteroresistance on treatment outcomes of people with drug-resistant TB |
| title_short | Impact of heteroresistance on treatment outcomes of people with drug-resistant TB |
| title_sort | impact of heteroresistance on treatment outcomes of people with drug resistant tb |
| topic | drug resistance-associated mutations dr-tb tuberculosis |
| url | https://www.ingentaconnect.com/contentone/iuatld/ijtldo/2024/00000001/00000010/art00007 |
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