학술논문
Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance
Document Type
article
Author
Stagg, Helen R; Bothamley, Graham H; Davidson, Jennifer A; Kunst, Heinke; Lalor, Maeve K; Lipman, Marc C; Loutet, Miranda G; Lozewicz, Stefan; Mohiyuddin, Tehreem; Abbara, Aula; Alexander, Eliza; Booth, Helen; Creer, Dean D; Harris, Ross J; Kon, Onn Min; Loebinger, Michael R; McHugh, Timothy D; Milburn, Heather J; Palchaudhuri, Paramita; Phillips, Patrick PJ; Schmok, Erik; Taylor, Lucy; Abubakar, Ibrahim; Baker, Lucy V; Barrett, Jessica C; Burgess, Helen; Cosgrove, Catherine; Dunleavy, Anne; Francis, Marie; Gupta, Urmi; Hamid, Shahid; Haselden, Brigitte M; Holden, Emma; Kahr, Vanessa; Lynn, William; Perrin, Felicity M; Rahman, Ananna; Soobratty, Mohammad R
Source
European Respiratory Journal. 54(4)
Subject
Language
Abstract
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. 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). 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). 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.