1. Fluoroquinolones and isoniazid-resistant tuberculosis: implications for the 2018 WHO guidance
- Author
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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, and Soobratty, Mohammad R
- Subjects
Biomedical and Clinical Sciences ,Clinical Sciences ,Tuberculosis ,Rare Diseases ,Antimicrobial Resistance ,Clinical Research ,Infectious Diseases ,Orphan Drug ,Infection ,Good Health and Well Being ,Adolescent ,Adult ,Aged ,Antitubercular Agents ,Drug Therapy ,Combination ,Duration of Therapy ,Ethambutol ,Female ,Fluoroquinolones ,Humans ,Isoniazid ,Levofloxacin ,Logistic Models ,London ,Male ,Middle Aged ,Practice Guidelines as Topic ,Pyrazinamide ,Recurrence ,Retrospective Studies ,Rifampin ,Treatment Failure ,Tuberculosis ,Multidrug-Resistant ,World Health Organization ,Young Adult ,London INH-R TB study group ,Medical and Health Sciences ,Respiratory System ,Cardiovascular medicine and haematology - 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.
- Published
- 2019