Fluoroquinolones and isoniazid resistant TB: implications for the 2018 WHO guidance

Autor: Stagg, HR, Bothamley, GH, Davidson, JA, Kunst, H, Lalor, MK, Lipman, MC, Loutet, MG, Lozewicz, S, Mohiyuddin, T, Abbara, A, Alexander, E, Booth, H, Creer, DD, Harris, RJ, Kon, OM, Loebinger, MR, McHugh, TD, Milburn, HJ, Palchaudhuri, P, Phillips, PPJ, Schmok, E, Taylor, L, Abubakar, I, on behalf of the London INH-R TB study group
Jazyk: angličtina
Rok vydání: 2019
Zdroj: Stagg, HR, Bothamley, GH, Davidson, JA, Kunst, H, Lalor, MK, Lipman, MC, Loutet, MG, Lozewicz, S, Mohiyuddin, T, Abbara, A, Alexander, E, Booth, H, Creer, DD, Harris, RJ, Kon, OM, Loebinger, MR, McHugh, TD, Milburn, HJ, Palchaudhuri, P, Phillips, PPJ, Schmok, E, Taylor, L, Abubakar, I & on behalf of the London INH-R TB study group 2019, ' Fluoroquinolones and isoniazid resistant TB: implications for the 2018 WHO guidance ', European Respiratory Journal . https://doi.org/10.1183/13993003.00982-2019
DOI: 10.1183/13993003.00982-2019
Popis: 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.
Databáze: OpenAIRE