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The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance

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dc.contributor.author Van Deun, A. en_US
dc.contributor.author Decroo, T. en_US
dc.contributor.author Kya Jai Maug, A. en_US
dc.contributor.author Hossain, M. A. en_US
dc.contributor.author Gumusboga, M. en_US
dc.contributor.author Mulders, W. en_US
dc.contributor.author Ortuno-Gutierrez, N. en_US
dc.contributor.author Lynen, L. en_US
dc.contributor.author de Jong, B. C. en_US
dc.contributor.author Rieder, H. L. en_US
dc.date.accessioned 2020-08-25T09:38:15Z
dc.date.available 2020-08-25T09:38:15Z
dc.date.issued 2020 en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.doi http://dx.doi.org/10.1371/journal.pone.0233500 en_US
dc.identifier.other ITG-B1A; ITG-C2A; ITG-B5A; ITG-C8A; ITG-B9A; MULTI; DBM; U-MYCOB; CLINIC; U-INFDIS; JIF; DOI; CPDF; PMC; Abstract; ITMPUB; DSPACE68 en_US
dc.identifier.uri http://hdl.handle.net/10390/10895
dc.description.abstract BACKGROUND: Meta-analyses on impact of isoniazid-resistant tuberculosis informed the World Health Organization recommendation of a levofloxacin-strengthened rifampicin-based regimen. We estimated the effect of initial rifampicin resistance (Rr) and/or isoniazid resistance (Hr) on treatment failure or relapse. We also determined the frequency of missed initial and acquired Rr to estimate the impact of true Hr. METHODS: Retrospective analysis of 7291 treatment episodes with known initial isoniazid and rifampicin status obtained from individual patient databases maintained by the Damien Foundation Bangladesh over 20 years. Drug susceptibility test results were confirmed by the programme's designated supra-national tuberculosis laboratory. To detect missed Rr among isolates routinely classified as Hr, rpoB gene sequencing was done randomly and on a sample selected for suspected missed Rr. RESULTS: Initial Hr caused a large recurrence excess after the 8-month regimen for new cases (rifampicin for two months), but had little impact on rifampicin-throughout regimens: (6 months, new cases; 3.8%; OR 0.8, 95%CI:0.3,2.8; 8 months, retreatment cases: 7.3%, OR 1.8; 95%CI:1.3,2.6). Rr was missed in 7.6% of randomly selected "Hr" strains. Acquired Rr was frequent among recurrences on rifampicin-throughout regimens, particularly after the retreatment regimen (31.9%). It was higher in mono-Hr (29.3%; aOR 3.5, 95%CI:1.5,8.5) and poly-Hr (53.3%; aOR 10.2, 95%CI 4.4,23.7) than in susceptible tuberculosis, but virtually absent after the 8-month new case regimen. Comparing Bangladesh (low Rr prevalence) with a high Rr prevalence setting,true Hr corrected for missed Rr caused only 2-3 treatment failures per 1000 TB cases (of whom 27% were retreatments) in both. CONCLUSIONS: Our analysis reveals a non-negligible extent of misclassifying as isoniazid resistance of what is actually missed multidrug-resistant tuberculosis. Recommending for such cases a "strengthened" regimen containing a fluoroquinolone provokes a direct route to extensive resistance while offering little benefit against the minor role of true Hr tuberculosis in rifampicin-throughout first-line regimen. en_US
dc.language English en_US
dc.relation.uri http://www.ncbi.nlm.nih.gov/pubmed/32421749 en_US
dc.subject Tuberculosis en_US
dc.subject Bacterial diseases en_US
dc.subject Treatment en_US
dc.subject Rifampicin en_US
dc.subject Isoniazid en_US
dc.subject Drug resistance en_US
dc.subject Bangladesh en_US
dc.subject Asia-South en_US
dc.title The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance en_US
dc.type Article-E en_US
dc.citation.issue 5 en_US
dc.citation.jtitle PLoS ONE en_US
dc.citation.volume 15 en_US
dc.citation.pages e0233500 en_US
dc.citation.abbreviation PLoS ONE en_US


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