RT Journal Article
SR Electronic
T1 Fluoroquinolones and isoniazid resistant TB: implications for the 2018 WHO guidance
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1900982
DO 10.1183/13993003.00982-2019
A1 Helen R. Stagg
A1 Graham H. Bothamley
A1 Jennifer A. Davidson
A1 Heinke Kunst
A1 Maeve K. Lalor
A1 Marc C. Lipman
A1 Miranda G. Loutet
A1 Stefan Lozewicz
A1 Tehreem Mohiyuddin
A1 Aula Abbara
A1 Eliza Alexander
A1 Helen Booth
A1 Dean D. Creer
A1 Ross J. Harris
A1 Onn Min Kon
A1 Michael R. Loebinger
A1 Timothy D. McHugh
A1 Heather J. Milburn
A1 Paramita Palchaudhuri
A1 Patrick P.J. Phillips
A1 Erik Schmok
A1 Lucy Taylor
A1 Ibrahim Abubakar
A1 Lucy V. Baker
A1 Jessica C. Barrett
A1 Helen Burgess
A1 Catherine Cosgrove
A1 Anne Dunleavy
A1 Marie Francis
A1 Urmi Gupta
A1 Shahid Hamid
A1 Brigitte M. Haselden
A1 Emma Holden
A1 Vanessa Kahr
A1 William Lynn
A1 Felicity M. Perrin
A1 Ananna Rahman
A1 Mohammad R. Soobratty
A1 ,
YR 2019
UL http://erj.ersjournals.com/content/early/2019/07/03/13993003.00982-2019.abstract
AB 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, 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% confidence interval 0.60–1.82], p-value 0.87; cluster NHS Trust). Results varied minimally in a multivariable model. This odds ratio dropped (0.57 [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 TB with or without a Fq. This regimen may result in fewer adverse events than the WHO recommendations.FootnotesThis manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.Conflict of interest: Dr. Stagg reports grants from National Institute for Health Research, UK, during the conduct of the study; grants from Medical Research Council, UK and Korea Health Industry Development Institute, outside the submitted work.Conflict of interest: Prof. Bothamley has nothing to disclose.Conflict of interest: Ms Davidson has nothing to disclose.Conflict of interest: Dr. Kunst has nothing to disclose.Conflict of interest: Dr. Lalor has nothing to disclose.Conflict of interest: Dr. Lipman has nothing to disclose.Conflict of interest: Ms. Loutet has nothing to disclose.Conflict of interest: Dr. Lozewicz has nothing to disclose.Conflict of interest: Ms. Mohiyuddin has nothing to disclose.Conflict of interest: Dr. Abbara has nothing to disclose.Conflict of interest: Dr. Alexander reports personal fees from Insmed, outside the submitted work.Conflict of interest: Dr. Booth has nothing to disclose.Conflict of interest: Dr. Creer has nothing to disclose.Conflict of interest: Mr. Harris has nothing to disclose.Conflict of interest: Dr. Kon has nothing to disclose.Conflict of interest: Dr. Loebinger has nothing to disclose.Conflict of interest: Dr. McHugh has nothing to disclose.Conflict of interest: Prof Milburn has nothing to disclose.Conflict of interest: Dr. Palchaudhuri has nothing to disclose.Conflict of interest: Dr. Phillips has nothing to disclose.Conflict of interest: Dr. Schmok has nothing to disclose.Conflict of interest: Lucy Taylor has nothing to disclose.Conflict of interest: Dr. Abubakar reports grants from NIHR, grants from MRC, outside the submitted work.Conflict of interest: Dr. Baker has nothing to disclose.Conflict of interest: Dr. Barrett has nothing to disclose.Conflict of interest: Dr. Burgess has nothing to disclose.Conflict of interest: Dr. Cosgrove has nothing to disclose.Conflict of interest: Dr. Dunleavy has nothing to disclose.Conflict of interest: Ms. Francis reports grants from Clinical Research Network, UK, during the conduct of the study.Conflict of interest: Dr. Gupta has nothing to disclose.Conflict of interest: Dr. Hamid has nothing to disclose.Conflict of interest: Dr. Haselden has nothing to disclose.Conflict of interest: Dr. Holden has nothing to disclose.Conflict of interest: Dr. Kahr has nothing to disclose.Conflict of interest: Dr. Lynn has nothing to disclose.Conflict of interest: Dr. Perrin has nothing to disclose.Conflict of interest: Dr. Rahman has nothing to disclose.Conflict of interest: Mr. Soobratty has nothing to disclose.