ArticlePloS one2020
The perceived impact of isoniazid resistance on outcome of first-line rifampicin-throughout regimens is largely due to missed rifampicin resistance.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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12 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- Effectiveness and safety of Levofloxacin containing regimen in the treatment of Isoniazid mono-resistant pulmonary Tuberculosis: a systematic review.Frontiers in medicine · 2023Pooled it
- Prevalence ofJournal of clinical tuberculosis and other mycobacterial diseases · 2023Article
- Continuous surveillance of drug-resistant TB burden in Rwanda: a retrospective cross-sectional study.International health · 2023Article
- Multidrug-resistant tuberculosis control in Rwanda overcomes a successful clone that causes most disease over a quarter century.Journal of clinical tuberculosis and other mycobacterial diseases · 2022Review
- Acquired rifampicin resistance during first TB treatment: magnitude, relative importance, risk factors and keys to control in low-income settings.JAC-antimicrobial resistance · 2022Article
- Tuberculosis Phenotypic and Genotypic Drug Susceptibility Testing and Immunodiagnostics: A Review.Frontiers in immunology · 2022Review
- Thin-Layer-Agar-Based Direct Phenotypic Drug Susceptibility Testing on Sputum in Eswatini Rapidly Detects Mycobacterium tuberculosis Growth and Rifampicin Resistance Otherwise Missed by WHO-Endorsed Diagnostic Tests.Antimicrobial agents and chemotherapy · 2021Article
- Comparison of first-line tuberculosis treatment outcomes between previously treated and new patients: a retrospective study in Machakos subcounty, Kenya.International health · 2021Article
- On the Consequences of Poorly Defined Breakpoints for Rifampin Susceptibility Testing of Mycobacterium tuberculosis Complex.Journal of clinical microbiology · 2021Article
- Case Report: Therapeutic Threshold for Rifampicin-Resistant Tuberculosis in a Patient from Maputo, Mozambique.The American journal of tropical medicine and hygiene · 2021Article
- Article
- Heteroresistance to rifampicin & isoniazid in clinical samples of patients with presumptive drug-resistant tuberculosis in Central India.The Indian journal of medical researchArticle
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMeta-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.
methodsRetrospective 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.
resultsInitial 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.
conclusionsOur 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.
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