Fluoroquinolones and isoniazid-resistant tuberculosis: Implications for the 2018 WHO guidance

Helen R. Stagg*, Graham H. Bothamley, Jennifer A. Davidson, Heinke Kunst, Maeve Lalor, Marc C. Lipman, Miranda G. Loutet, Stefan Lozewicz, Tehreem Mohiyuddin, Aula Abbara, Eliza Alexander, Helen Booth, Dean D. Creer, Ross J. Harris, Onn Min Kon, Michael R. Loebinger, Timothy D. McHugh, Heather J. Milburn, Paramita Palchaudhuri, Patrick P.J. PhillipsErik Schmok, Lucy Taylor, Ibrahim Abubakar

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

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Introduction: 2018 World Health Organization (WHO) guidelines for the treatment of isoniazid (H)-resistant (Hr) tuberculosis recommend a four-drug regimen: Rifampicin (R), ethambutol (E), pyrazinamide (Z) and levofloxacin (Lfx), with or without H ([H]RZE-Lfx). This is used once Hr is known, such that patients complete 6 months of Lfx (≫6[H]RZE-6Lfx). This cohort study assessed the impact of fluoroquinolones (Fq) on treatment effectiveness, accounting for Hr mutations and degree of phenotypic resistance. Methods: This was a retrospective cohort study of 626 Hr tuberculosis patients notified in London, 2009- 2013. Regimens were described and logistic regression undertaken of the association between regimen and negative regimen-specific outcomes (broadly, death due to tuberculosis, treatment failure or disease recurrence). Results: Of 594 individuals with regimen information, 330 (55.6%) were treated with (H)RfZE (Rf=rifamycins) and 211 (35.5%) with (H)RfZE-Fq. The median overall treatment period was 11.9 months and median Z duration 2.1 months. In a univariable logistic regression model comparing (H)RfZE with and without Fqs, there was no difference in the odds of a negative regimen-specific outcome (baseline (H) RfZE, cluster-specific odds ratio 1.05 (95% CI 0.60-1.82), p=0.87; cluster NHS trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57, 95% CI 0.14-2.28) when Hr genotype was included, but this analysis lacked power ( p=0.42). Conclusions: In a high-income setting, we found a 12-month (H)RfZE regimen with a short Z duration to be similarly effective for Hr tuberculosis with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.

Original languageEnglish
Article number1900982
JournalEuropean Respiratory Journal
Issue number4
Publication statusPublished - 1 Oct 2019

Bibliographical note

Funding Information:
Conflict of interest: H.R. Stagg reports grants from National Institute for Health Research, UK (PDF-2014-07-008), during the conduct of the study; grants from Medical Research Council, UK (MC_PC_17101) and Korea Health Industry Development Institute, outside the submitted work. G.H. Bothamley has nothing to disclose. J.A. Davidson has nothing to disclose. H. Kunst has nothing to disclose. M.K. Lalor has nothing to disclose. M.C. Lipman has nothing to disclose. M.G. Loutet has nothing to disclose. S. Lozewicz has nothing to disclose. T. Mohiyuddin has nothing to disclose. A. Abbara has nothing to disclose. E. Alexander reports personal fees for advisory board work from Insmed, outside the submitted work. H. Booth has nothing to disclose. D.D. Creer has nothing to disclose. R.J. Harris has nothing to disclose. O.M. Kon has nothing to disclose. M.R. Loebinger has nothing to disclose. T.D. McHugh has nothing to disclose. H.J. Milburn has nothing to disclose. P. Palchaudhuri has nothing to disclose. P.P.J. Phillips has nothing to disclose. E. Schmok has nothing to disclose. L. Taylor has nothing to disclose. I. Abubakar reports grants from NIHR and MRC, outside the submitted work.

Funding Information:
Support statement: This report is independent research supported by the National Institute for Health Research (Post Doctoral Fellowship, Helen R. Stagg, PDF-2014-07-008). The views expressed in this publication are those of the author (s) and not necessarily those of the NHS, the National Institute for Health Research or the Department of Health. The sponsors had no role in the study design; collection, analysis and interpretation of the data; writing of the report; and in the decision to submit the paper for publication. Funding information for this article has been deposited with the Crossref Funder Registry.

Publisher Copyright:
© ERS 2019.


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