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Title
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Initial resistance to companion drugs should not be considered an exclusion criterion for the shorter multidrug-resistant tuberculosis treatment regimen
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Author
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Abstract
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| 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/rifampicin-resistant (RR) 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 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. (C) 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. |
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Language
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English
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Source (journal)
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International journal of infectious diseases / International Society for Infectious Diseases. - Hamilton, Ont.
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Publication
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Hamilton, Ont.
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2020
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ISSN
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1201-9712
1878-3511
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DOI
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10.1016/J.IJID.2020.08.042
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Volume/pages
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100
(2020)
, p. 357-365
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ISI
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000612537700062
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Pubmed ID
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32829049
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Full text (Publisher's DOI)
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Full text (open access)
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