Effectiveness and Safety of Standardised Shorter Regimens for Multidrug-Resistant Tuberculosis: Individual Patient Data and Aggregate Data Meta-Analyses
AuthorsAhmad Khan, F
du Cros, P
MetadataShow full item record
JournalThe European Respiratory Journal
AbstractWe assessed the effectiveness and safety of standardised, shorter multidrug-resistant tuberculosis (MDR-TB) regimens by pooling data from observational studies.Published studies were identified from medical databases; unpublished studies were identified from expert consultation. We conducted aggregate data meta-analyses to estimate pooled proportions of treatment outcomes and individual patient data (IPD) meta-regression to identify risk factors for unsuccessful treatment in patients treated with 9- to 12-month MDR-TB regimens composed of a second-line injectable, gatifloxacin/moxifloxacin, prothionamide, clofazimine, isoniazid, pyrazinamide and ethambutol.We included five studies in which 796 out of 1279 (62.2%) individuals with confirmed MDR-TB (98.4%) or rifampin-resistant TB (1.6%), and not previously exposed to second-line drugs, were eligible for shorter regimens. 669 out of 796 participants were successfully treated (83.0%, 95% CI 71.9-90.3%). In IPD meta-regression (three studies, n=497), failure/relapse was associated with fluoroquinolone resistance (crude OR 46, 95% CI 8-273), pyrazinamide resistance (OR 8, 95% CI 2-38) and no culture conversion by month 2 of treatment (OR 7, 95% CI 3-202). Two participants acquired extensive drug resistance. Four studies reported grade 3 or 4 adverse events in 55 out of 304 (18.1%) participants.Shorter regimens were effective in treating MDR-TB; however, there is uncertainty surrounding the generalisability of the high rate of treatment success to less selected populations, to programmatic settings and in the absence of drug susceptibility tests to key component drugs.
PublisherEuropean Respiratory Society
DescriptionWe regret that this article is behind a paywall.
- Delamanid, linezolid, levofloxacin, and pyrazinamide for the treatment of patients with fluoroquinolone-sensitive multidrug-resistant tuberculosis (Treatment Shortening of MDR-TB Using Existing and New Drugs, MDR-END): study protocol for a phase II/III, multicenter, randomized, open-label clinical trial.
- Authors: Lee M, Mok J, Kim DK, Shim TS, Koh WJ, Jeon D, Lee T, Lee SH, Kim JS, Park JS, Lee JY, Kim SY, Lee JH, Jo KW, Jhun BW, Kang YA, Ahn JH, Kim CK, Shin S, Song T, Shin SJ, Kim YR, Ahn H, Hahn S, Won HJ, Jang JY, Cho SN, Yim JJ
- Issue date: 2019 Jan 16
- Pyrazinamide may improve fluoroquinolone-based treatment of multidrug-resistant tuberculosis.
- Authors: Chang KC, Leung CC, Yew WW, Leung EC, Leung WM, Tam CM, Zhang Y
- Issue date: 2012 Nov
- Effectiveness and safety of clofazimine in multidrug-resistant tuberculosis: a nationwide report from Brazil.
- Authors: Dalcolmo M, Gayoso R, Sotgiu G, D'Ambrosio L, Rocha JL, Borga L, Fandinho F, Braga JU, Galesi VM, Barreira D, Sanchez DA, Dockhorn F, Centis R, Caminero JA, Migliori GB
- Issue date: 2017 Mar
- High effectiveness of a 12-month regimen for MDR-TB patients in Cameroon.
- Authors: Kuaban C, Noeske J, Rieder HL, Aït-Khaled N, Abena Foe JL, Trébucq A
- Issue date: 2015 May
- Treatment and outcomes in children with multidrug-resistant tuberculosis: A systematic review and individual patient data meta-analysis.
- Authors: Harausz EP, Garcia-Prats AJ, Law S, Schaaf HS, Kredo T, Seddon JA, Menzies D, Turkova A, Achar J, Amanullah F, Barry P, Becerra M, Chan ED, Chan PC, Ioana Chiotan D, Crossa A, Drobac PC, Fairlie L, Falzon D, Flood J, Gegia M, Hicks RM, Isaakidis P, Kadri SM, Kampmann B, Madhi SA, Marais E, Mariandyshev A, Méndez-Echevarría A, Moore BK, Nargiza P, Ozere I, Padayatchi N, Ur-Rehman S, Rybak N, Santiago-Garcia B, Shah NS, Sharma S, Shim TS, Skrahina A, Soriano-Arandes A, van den Boom M, van der Werf MJ, van der Werf TS, Williams B, Yablokova E, Yim JJ, Furin J, Hesseling AC, Collaborative Group for Meta-Analysis of Paediatric Individual Patient Data in MDR-TB.
- Issue date: 2018 Jul