The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2020-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0233500 |
| _version_ | 1818678020252106752 |
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| author | Armand Van Deun Tom Decroo Aung Kya Jai Maug Mohamed Anwar Hossain Murid Gumusboga Wim Mulders Nimer Ortuño-Gutiérrez Lutgarde Lynen Bouke C de Jong Hans L Rieder |
| author_facet | Armand Van Deun Tom Decroo Aung Kya Jai Maug Mohamed Anwar Hossain Murid Gumusboga Wim Mulders Nimer Ortuño-Gutiérrez Lutgarde Lynen Bouke C de Jong Hans L Rieder |
| author_sort | Armand Van Deun |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-17T09:08:37Z |
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| id | doaj.art-31f1fb6a08e74fa3b5a40a8e7044cd3f |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-17T09:08:37Z |
| publishDate | 2020-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-31f1fb6a08e74fa3b5a40a8e7044cd3f2022-12-21T21:55:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-01155e023350010.1371/journal.pone.0233500The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance.Armand Van DeunTom DecrooAung Kya Jai MaugMohamed Anwar HossainMurid GumusbogaWim MuldersNimer Ortuño-GutiérrezLutgarde LynenBouke C de JongHans L RiederBACKGROUND: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.https://doi.org/10.1371/journal.pone.0233500 |
| spellingShingle | Armand Van Deun Tom Decroo Aung Kya Jai Maug Mohamed Anwar Hossain Murid Gumusboga Wim Mulders Nimer Ortuño-Gutiérrez Lutgarde Lynen Bouke C de Jong Hans L Rieder The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance. PLoS ONE |
| title | The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance. |
| title_full | The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance. |
| title_fullStr | The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance. |
| title_full_unstemmed | The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance. |
| title_short | The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance. |
| title_sort | perceived impact of isoniazid resistance on outcome of first line rifampicin throughout regimens is largely due to missed rifampicin resistance |
| url | https://doi.org/10.1371/journal.pone.0233500 |
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