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Title
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Identifying isoniazid resistance markers to guide inclusion of high-dose isoniazid in tuberculosis treatment regimens
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Author
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Abstract
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| Objectives: Effective use of antibiotics is critical to control the global tuberculosis pandemic. High-dose isoniazid (INH) can be effective in the presence of low-level resistance. We performed a systematic literature review to improve our understanding of the differential impact of genomic Mycobacterium tuberculosis (Mtb) variants on the level of INH resistance. The following online databases were searched: PubMed, Web of Science and Embase. Articles reporting on clinical Mtb isolates with linked genotypic and phenotypic data and reporting INH resistance levels were eligible for inclusion. Methods: All genomic regions reported in the eligible studies were included in the analysis, including: katG, inhA, ahpC, oxyR-ahpC, furA, fabG1, kasA, rv1592c, iniA, iniB, iniC, rv0340, rv2242 and nat. The level of INH resistance was determined by MIC: low-level resistance was defined as 0.1-0.4 mu g/mL on liquid and 0.2-1.0 mu g/mL on solid media, high-level resistance as >0.4 mu g/mL on liquid and >1.0 mu g/mL on solid media. Results: A total of 1212 records were retrieved of which 46 were included. These 46 studies reported 1697 isolates of which 21% (n = 362) were INH susceptible, 17% (n = 287) had low-level, and 62% (n = 1048) high-level INH resistance. Overall, 24% (n = 402) of isolates were reported as wild type and 76% (n = 1295) had >= 1 relevant genetic variant. Among 1295 isolates with >= 1 variant, 78% (n = 1011) had a mutation in the katG gene. Of the 867 isolates with a katG mutation in codon 315, 93% (n = 810) had high-level INH resistance. In contrast, only 50% (n = 72) of the 144 isolates with a katG variant not in the 315-position had high-level resistance. Of the 284 isolates with >= 1 relevant genetic variant and wild type katG gene, 40% (n = 114) had high-level INH resistance. Conclusions: Presence of a variant in the katG gene is a good marker of high-level INH resistance only if located in codon 315. (C) 2020 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved. |
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Language
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English
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Source (journal)
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Clinical microbiology and infection / European Society of Clinical Microbiology and Infectious Diseases. - Oxford
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Publication
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Oxford
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Elsevier sci ltd
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2020
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ISSN
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1198-743X
[print]
1469-0691
[online]
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DOI
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10.1016/J.CMI.2020.07.004
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Volume/pages
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26
:10
(2020)
, p. 1332-1337
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ISI
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000573452600010
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Pubmed ID
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32653663
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Full text (Publisher's DOI)
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Full text (open access)
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