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Eur Respir J. 2019 Oct 10;54(4). pii: 1900982. doi: 10.1183/13993003.00982-2019. Print 2019 Oct.

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

Author information

1
Institute for Global Health, University College London, London, UK helen.stagg@ed.ac.uk.
2
Usher Institute of Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
3
Respiratory Medicine, Homerton University Hospital, London, UK.
4
These authors contributed equally to this manuscript and are presented alphabetically.
5
Tuberculosis Unit, National Infection Service, Public Health England, London, UK.
6
Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
7
Institute for Global Health, University College London, London, UK.
8
Respiratory Medicine, Royal Free Hospital, London, UK.
9
UCL Respiratory, Division of Medicine, University College London.
10
Respiratory Medicine, North Middlesex University Hospital, London, UK.
11
Infectious Diseases, London North West University Healthcare NHS Trust, London, UK.
12
National Mycobacterial Reference Service South, Public Health England, London, UK.
13
Tuberculosis Service, University College London Hospitals/Whittington Health, London, UK.
14
Respiratory Medicine, Barnet General Hospital, Royal Free London NHS Foundation Trust, London, UK.
15
Statistics, Modelling and Economics Department, Public Health England, London, UK.
16
TB Service, Imperial College Healthcare, London, UK.
17
Respiratory Medicine, Chelsea and Westminster Hospital, London, UK.
18
Centre for Clinical Microbiology, University College London, London, UK.
19
Respiratory Medicine, Guy's and St Thomas' Hospital, London, UK.
20
Respiratory Services, Queen Elizabeth Hospital, London, UK.
21
Dept of Medicine and Dept of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.

Abstract

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.

Conflict of interest statement

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. Conflict of interest: G.H. Bothamley has nothing to disclose. Conflict of interest: J.A. Davidson has nothing to disclose. Conflict of interest: H. Kunst has nothing to disclose. Conflict of interest: M.K. Lalor has nothing to disclose. Conflict of interest: M.C. Lipman has nothing to disclose. Conflict of interest: M.G. Loutet has nothing to disclose. Conflict of interest: S. Lozewicz has nothing to disclose. Conflict of interest: T. Mohiyuddin has nothing to disclose. Conflict of interest: A. Abbara has nothing to disclose. Conflict of interest: E. Alexander reports personal fees for advisory board work from Insmed, outside the submitted work. Conflict of interest: H. Booth has nothing to disclose. Conflict of interest: D.D. Creer has nothing to disclose. Conflict of interest: R.J. Harris has nothing to disclose. Conflict of interest: O.M. Kon has nothing to disclose. Conflict of interest: M.R. Loebinger has nothing to disclose. Conflict of interest: T.D. McHugh has nothing to disclose. Conflict of interest: H.J. Milburn has nothing to disclose. Conflict of interest: P. Palchaudhuri has nothing to disclose. Conflict of interest: P.P.J. Phillips has nothing to disclose. Conflict of interest: E. Schmok has nothing to disclose. Conflict of interest: L. Taylor has nothing to disclose. Conflict of interest: I. Abubakar reports grants from NIHR and MRC, outside the submitted work.

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