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dc.contributor.authorFregonese, Federica
dc.contributor.authorAhuja, Shama D
dc.contributor.authorAkkerman, Onno W
dc.contributor.authorArakaki-Sanchez, Denise
dc.contributor.authorAyakaka, Irene
dc.contributor.authorBaghaei, Parvaneh
dc.contributor.authorBang, Didi
dc.contributor.authorBastos, Mayara
dc.contributor.authorBenedetti, Andrea
dc.contributor.authorBonnet, Maryline
dc.contributor.authorCattamanchi, Adithya
dc.contributor.authorCegielski, Peter
dc.contributor.authorChien, Jung-Yien
dc.contributor.authorCox, Helen
dc.contributor.authorDedicoat, Martin
dc.contributor.authorErkens, Connie
dc.contributor.authorEscalante, Patricio
dc.contributor.authorFalzon, Dennis
dc.contributor.authorGarcia-Prats, Anthony J
dc.contributor.authorGegia, Medea
dc.contributor.authorGillespie, Stephen H
dc.contributor.authorGlynn, Judith R
dc.contributor.authorGoldberg, Stefan
dc.contributor.authorGriffith, David
dc.contributor.authorJacobson, Karen R
dc.contributor.authorJohnston, James C
dc.contributor.authorJones-López, Edward C
dc.contributor.authorKhan, Awal
dc.contributor.authorKoh, Won-Jung
dc.contributor.authorKritski, Afranio
dc.contributor.authorLan, Zhi Yi
dc.contributor.authorLee, Jae Ho
dc.contributor.authorLi, Pei Zhi
dc.contributor.authorMaciel, Ethel L
dc.contributor.authorGalliez, Rafael Mello
dc.contributor.authorMerle, Corinne S C
dc.contributor.authorMunang, Melinda
dc.contributor.authorNarendran, Gopalan
dc.contributor.authorNguyen, Viet Nhung
dc.contributor.authorNunn, Andrew
dc.contributor.authorOhkado, Akihiro
dc.contributor.authorPark, Jong Sun
dc.contributor.authorPhillips, Patrick P J
dc.contributor.authorPonnuraja, Chinnaiyan
dc.contributor.authorReves, Randall
dc.contributor.authorRomanowski, Kamila
dc.contributor.authorSeung, Kwonjune
dc.contributor.authorSchaaf, H Simon
dc.contributor.authorSkrahina, Alena
dc.contributor.authorSoolingen, Dick van
dc.contributor.authorTabarsi, Payam
dc.contributor.authorTrajman, Anete
dc.contributor.authorTrieu, Lisa
dc.contributor.authorBanurekha, Velayutham V
dc.contributor.authorViiklepp, Piret
dc.contributor.authorWang, Jann-Yuan
dc.contributor.authorYoshiyama, Takashi
dc.contributor.authorMenzies, Dick
dc.identifier.citationFregonese , F , Ahuja , S D , Akkerman , O W , Arakaki-Sanchez , D , Ayakaka , I , Baghaei , P , Bang , D , Bastos , M , Benedetti , A , Bonnet , M , Cattamanchi , A , Cegielski , P , Chien , J-Y , Cox , H , Dedicoat , M , Erkens , C , Escalante , P , Falzon , D , Garcia-Prats , A J , Gegia , M , Gillespie , S H , Glynn , J R , Goldberg , S , Griffith , D , Jacobson , K R , Johnston , J C , Jones-López , E C , Khan , A , Koh , W-J , Kritski , A , Lan , Z Y , Lee , J H , Li , P Z , Maciel , E L , Galliez , R M , Merle , C S C , Munang , M , Narendran , G , Nguyen , V N , Nunn , A , Ohkado , A , Park , J S , Phillips , P P J , Ponnuraja , C , Reves , R , Romanowski , K , Seung , K , Schaaf , H S , Skrahina , A , Soolingen , D V , Tabarsi , P , Trajman , A , Trieu , L , Banurekha , V V , Viiklepp , P , Wang , J-Y , Yoshiyama , T & Menzies , D 2018 , ' Comparison of different treatments for isoniazid-resistant tuberculosis : an individual patient data meta-analysis ' , The Lancet Respiratory Medicine , vol. 6 , no. 4 , pp. 265-275 .
dc.identifier.otherPURE: 252624952
dc.identifier.otherPURE UUID: 81c56b8e-958d-4e86-8e53-846ff037f0f6
dc.identifier.otherRIS: urn:6EF2F691469D9CED5B1CB145DE05A6CA
dc.identifier.otherScopus: 85044150768
dc.identifier.otherORCID: /0000-0001-6537-7712/work/43149817
dc.identifier.otherWOS: 000428231000024
dc.descriptionFunding: World Health Organization and Canadian Institutes of Health Research.en
dc.description.abstractBackground: Isoniazid-resistant, rifampicin-susceptible (INH-R) tuberculosis is the most common form of drug resistance, and is associated with failure, relapse, and acquired rifampicin resistance if treated with first-line anti-tuberculosis drugs. The aim of the study was to compare success, mortality, and acquired rifampicin resistance in patients with INH-R pulmonary tuberculosis given different durations of rifampicin, ethambutol, and pyrazinamide (REZ); a fluoroquinolone plus 6 months or more of REZ; and streptomycin plus a core regimen of REZ. Methods: Studies with regimens and outcomes known for individual patients with INH-R tuberculosis were eligible, irrespective of the number of patients if randomised trials, or with at least 20 participants if a cohort study. Studies were identified from two relevant systematic reviews, an updated search of one of the systematic reviews (for papers published between April 1, 2015, and Feb 10, 2016), and personal communications. Individual patient data were obtained from authors of eligible studies. The individual patient data meta-analysis was performed with propensity score matched logistic regression to estimate adjusted odds ratios (aOR) and risk differences of treatment success (cure or treatment completion), death during treatment, and acquired rifampicin resistance. Outcomes were measured across different treatment regimens to assess the effects of: different durations of REZ (≤6 months vs >6 months); addition of a fluoroquinolone to REZ (fluoroquinolone plus 6 months or more of REZ vs 6 months or more of REZ); and addition of streptomycin to REZ (streptomycin plus 6 months of rifampicin and ethambutol and 1–3 months of pyrazinamide vs 6 months or more of REZ). The overall quality of the evidence was assessed using GRADE methodology. Findings: Individual patient data were requested for 57 cohort studies and 17 randomised trials including 8089 patients with INH-R tuberculosis. We received 33 datasets with 6424 patients, of which 3923 patients in 23 studies received regimens related to the study objectives. Compared with a daily regimen of 6 months of (H)REZ (REZ with or without isoniazid), extending the duration to 8–9 months had similar outcomes; as such, 6 months or more of (H)REZ was used for subsequent comparisons. Addition of a fluoroquinolone to 6 months or more of (H)REZ was associated with significantly greater treatment success (aOR 2·8, 95% CI 1·1–7·3), but no significant effect on mortality (aOR 0·7, 0·4–1·1) or acquired rifampicin resistance (aOR 0·1, 0·0–1·2). Compared with 6 months or more of (H)REZ, the standardised retreatment regimen (2 months of streptomycin, 3 months of pyrazinamide, and 8 months of isoniazid, rifampicin, and ethambutol) was associated with significantly worse treatment success (aOR 0·4, 0·2–0·7). The quality of the evidence was very low for all outcomes and treatment regimens assessed, owing to the observational nature of most of the data, the diverse settings, and the imprecision of estimates. Interpretation: In patients with INH-R tuberculosis, compared with treatment with at least 6 months of daily REZ, addition of a fluoroquinolone was associated with better treatment success, whereas addition of streptomycin was associated with less treatment success; however, the quality of the evidence was very low. These results support the conduct of randomised trials to identify the optimum regimen for this important and common form of drug-resistant tuberculosis. Funding World Health Organization and Canadian Institutes of Health Research.
dc.relation.ispartofThe Lancet Respiratory Medicineen
dc.rightsCopyright © 2018, World Health Organization. Published by Elsevier Ltd. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at
dc.subjectRA0421 Public health. Hygiene. Preventive Medicineen
dc.titleComparison of different treatments for isoniazid-resistant tuberculosis : an individual patient data meta-analysisen
dc.typeJournal articleen
dc.contributor.institutionUniversity of St Andrews.School of Medicineen
dc.contributor.institutionUniversity of St Andrews.Infection and Global Health Divisionen
dc.contributor.institutionUniversity of St Andrews.Global Health Implementation Groupen
dc.contributor.institutionUniversity of St Andrews.Gillespie Groupen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.contributor.institutionUniversity of St Andrews.Infection Groupen
dc.description.statusPeer revieweden

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