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Initial resistance to companion drugs should not be considered an exclusion criterion for the multidrug-resistant tuberculosis shorter treatment regimen
Lempens, P. Decroo, T. Aung, K.J.M. Hossain, M.A. Rigouts, L. Meehan, Conor J. Van Deun, A. de Jong, B.C.
Lempens, P.
Decroo, T.
Aung, K.J.M.
Hossain, M.A.
Rigouts, L.
Meehan, Conor J.
Van Deun, A.
de Jong, B.C.
Publication Date
2020-08
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© 2020 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)
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openAccess
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16/08/2020
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Abstract
We investigated whether companion drug resistance was associated with adverse outcome of the shorter MDR-TB regimen in Bangladesh, after adjusting for fluoroquinolone resistance.
MDR/RR-TB patients registered for treatment with a standardized gatifloxacin-based shorter MDR-TB regimen were selected for the study. Drug resistance was determined using the proportion method, gatifloxacin and isoniazid minimum inhibitory concentration testing for selected isolates, and whole genome sequencing.
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 TB, non-eligibility to the shorter MDR-TB regimen (initial resistance to either pyrazinamide, ethionamide, or ethambutol) was not associated with adverse outcome (aOR 1.01; 95%CI 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 TB.
Our results suggest that resistance to companion drugs of the shorter MDR-TB 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, and possibly kanamycin resistance.
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Citation
Lempens P, Decroo T, Aung KJM et al (2020) Initial resistance to companion drugs should not be considered an exclusion criterion for the multidrug-resistant tuberculosis shorter treatment regimen. International Journal Of Infectious Diseases. 100: 357-365.
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