Initial resistance to companion drugs should not be considered an exclusion criterion for the shorter multidrug-resistant tuberculosis treatment regimen
Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved..
OBJECTIVES: We investigated whether companion drug resistance was associated with adverse outcomes of the shorter multidrug-resistant tuberculosis (MDR-TB) treatment regimen in Bangladesh after adjustment for fluoroquinolone resistance.
METHODS: MDR-TB/rifampicin-resistant tuberculosis patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB treatment regimen were selected for the study. Drug resistance was determined by the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole-genome sequencing.
RESULTS: Low-level fluoroquinolone resistance and high-level fluoroquinolone resistance were the most important predictors of adverse outcomes, with pyrazinamide resistance having a significant yet lower impact. In patients with fluoroquinolone-/second-line-injectable-susceptible tuberculosis, non-eligibility for the shorter MDR-TB treatment regimen (initial resistance to pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (adjusted odds ratio 1.01; 95% confidence interval 0.4-2.8). Kanamycin resistance was uncommon (1.3%). Increasing levels of resistance to isoniazid predicted treatment failure, also in a subgroup of patients with high-level fluoroquinolone-resistant tuberculosis.
CONCLUSIONS: Our results suggest that resistance to companion drugs in the shorter MDR-TB treatment regimen, except kanamycin resistance, is of no clinical importance as long as fluoroquinolone susceptibility is preserved. Hence, contrary to current WHO guidelines, exclusions to the standard regimen are justified only in the case of fluoroquinolone resistance. and possibly kanamycin resistance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:100 |
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| Enthalten in: |
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases - 100(2020) vom: 28. Nov., Seite 357-365 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Lempens, Pauline [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 26.01.2021 Date Revised 10.11.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.ijid.2020.08.042 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM314026819 |
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| 100 | 1 | |a Lempens, Pauline |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Initial resistance to companion drugs should not be considered an exclusion criterion for the shorter multidrug-resistant tuberculosis treatment regimen |
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| 500 | |a Date Completed 26.01.2021 | ||
| 500 | |a Date Revised 10.11.2021 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved. | ||
| 520 | |a OBJECTIVES: We investigated whether companion drug resistance was associated with adverse outcomes of the shorter multidrug-resistant tuberculosis (MDR-TB) treatment regimen in Bangladesh after adjustment for fluoroquinolone resistance | ||
| 520 | |a METHODS: MDR-TB/rifampicin-resistant tuberculosis patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB treatment regimen were selected for the study. Drug resistance was determined by the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole-genome sequencing | ||
| 520 | |a RESULTS: Low-level fluoroquinolone resistance and high-level fluoroquinolone resistance were the most important predictors of adverse outcomes, with pyrazinamide resistance having a significant yet lower impact. In patients with fluoroquinolone-/second-line-injectable-susceptible tuberculosis, non-eligibility for the shorter MDR-TB treatment regimen (initial resistance to pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (adjusted odds ratio 1.01; 95% confidence interval 0.4-2.8). Kanamycin resistance was uncommon (1.3%). Increasing levels of resistance to isoniazid predicted treatment failure, also in a subgroup of patients with high-level fluoroquinolone-resistant tuberculosis | ||
| 520 | |a CONCLUSIONS: Our results suggest that resistance to companion drugs in the shorter MDR-TB treatment regimen, except kanamycin resistance, is of no clinical importance as long as fluoroquinolone susceptibility is preserved. Hence, contrary to current WHO guidelines, exclusions to the standard regimen are justified only in the case of fluoroquinolone resistance. and possibly kanamycin resistance | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Antimicrobial resistance | |
| 650 | 4 | |a Fluoroquinolones | |
| 650 | 4 | |a High-dose isoniazid | |
| 650 | 4 | |a Multidrug-resistant tuberculosis | |
| 650 | 4 | |a Shorter treatment regimen | |
| 650 | 4 | |a Whole-genome sequencing | |
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| 700 | 1 | |a Decroo, Tom |e verfasserin |4 aut | |
| 700 | 1 | |a Aung, Kya J M |e verfasserin |4 aut | |
| 700 | 1 | |a Hossain, Mohammad A |e verfasserin |4 aut | |
| 700 | 1 | |a Rigouts, Leen |e verfasserin |4 aut | |
| 700 | 1 | |a Meehan, Conor J |e verfasserin |4 aut | |
| 700 | 1 | |a Van Deun, Armand |e verfasserin |4 aut | |
| 700 | 1 | |a de Jong, Bouke C |e verfasserin |4 aut | |
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