Group 5 drugs for multidrug-resistant tuberculosis: Individual patient data meta-analysis

Greg J. Fox; Andrea Benedetti; Helen Cox; Won Jung Koh; Piret Viiklepp; Shama Ahuja; Geoffrey Pasvol; Dick Menzies; S. Ahuja; D. Ashkin; M. Avendaño; R. Banerjee; M. Bauer; M. G. Hollm-Delgado; M. Pai; L. Shah; J. N. Bayona; M. Becerra; M. Burgos; R. Centis; L. D'Ambrosio; G. B. Migliori; E. D. Chan; C. Y. Chiang; W. C M De Lange; R. Van Altena; T. S. Van Der Werf; K. De Riemer; N. H. Dung; D. Enarson; D. Falzon; R. M. Granich; K. Flanagan; J. Flood; N. Gandhi; L. Garcia-Garcia; T. H. Holtz; M. Iseman; M. J. Strand; L. G. Jarlsberg; S. Royce; S. Keshavjee; H. R. Kim; C. D. Mitnick; J. Lancaster; M. Van Der Walt; C. Lange; V. Leimane; V. Riekstina; C. C. Leung; J. Li; M. Narita; P. O'Riordan; D. Palmero; S. K. Park; J. Pena; C. Pérez-Guzmán; A. Ponce-De-Leon; J. Sifuentes-Osornio; M. I D Quelapio; T. E. Tupasi; J. Robert; H. S. Schaaf; K. J. Seung; S. S. Shin; T. S. Shim; Y. Shiraishi; G. Sotgiu; P. Tabarsi; M. H. Vargas; J. Westenhouse; W. W. Yew; J. J. Yim

doi:10.1183/13993003.00993-2016

Group 5 drugs for multidrug-resistant tuberculosis: Individual patient data meta-analysis

Greg J. Fox, Andrea Benedetti, Helen Cox, Won Jung Koh, Piret Viiklepp, Shama Ahuja, Geoffrey Pasvol, Dick Menzies, S. Ahuja, D. Ashkin, M. Avendaño, R. Banerjee, M. Bauer, M. G. Hollm-Delgado, M. Pai, L. Shah, J. N. Bayona, M. Becerra, M. Burgos, R. CentisL. D'Ambrosio, G. B. Migliori, E. D. Chan, C. Y. Chiang, W. C M De Lange, R. Van Altena, T. S. Van Der Werf, K. De Riemer, N. H. Dung, D. Enarson, D. Falzon, R. M. Granich, K. Flanagan, J. Flood, N. Gandhi, L. Garcia-Garcia, T. H. Holtz, M. Iseman, M. J. Strand, L. G. Jarlsberg, S. Royce, S. Keshavjee, H. R. Kim, C. D. Mitnick, J. Lancaster, M. Van Der Walt, C. Lange, V. Leimane, V. Riekstina, C. C. Leung, J. Li, M. Narita, P. O'Riordan, D. Palmero, S. K. Park, J. Pena, C. Pérez-Guzmán, A. Ponce-De-Leon, J. Sifuentes-Osornio, M. I D Quelapio, T. E. Tupasi, J. Robert, H. S. Schaaf, K. J. Seung, S. S. Shin, T. S. Shim, Y. Shiraishi, G. Sotgiu, P. Tabarsi, M. H. Vargas, J. Westenhouse, W. W. Yew, J. J. Yim

Research output: Contribution to journal › Article › peer-review

15 Citations (Scopus)

Abstract

The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB. Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death. Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study. The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

Original language	English
Article number	1600993
Journal	European Respiratory Journal
Volume	49
Issue number	1
DOIs	https://doi.org/10.1183/13993003.00993-2016
Publication status	Published - Jan 1 2017

ASJC Scopus subject areas

Pulmonary and Respiratory Medicine

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10.1183/13993003.00993-2016

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Fox, G. J., Benedetti, A., Cox, H., Koh, W. J., Viiklepp, P., Ahuja, S., Pasvol, G., Menzies, D., Ahuja, S., Ashkin, D., Avendaño, M., Banerjee, R., Bauer, M., Hollm-Delgado, M. G., Pai, M., Shah, L., Bayona, J. N., Becerra, M., Burgos, M., ... Yim, J. J. (2017). Group 5 drugs for multidrug-resistant tuberculosis: Individual patient data meta-analysis. European Respiratory Journal, 49(1), [1600993]. https://doi.org/10.1183/13993003.00993-2016

Group 5 drugs for multidrug-resistant tuberculosis : Individual patient data meta-analysis. / Fox, Greg J.; Benedetti, Andrea; Cox, Helen; Koh, Won Jung; Viiklepp, Piret; Ahuja, Shama; Pasvol, Geoffrey; Menzies, Dick; Ahuja, S.; Ashkin, D.; Avendaño, M.; Banerjee, R.; Bauer, M.; Hollm-Delgado, M. G.; Pai, M.; Shah, L.; Bayona, J. N.; Becerra, M.; Burgos, M.; Centis, R.; D'Ambrosio, L.; Migliori, G. B.; Chan, E. D.; Chiang, C. Y.; De Lange, W. C M; Van Altena, R.; Van Der Werf, T. S.; De Riemer, K.; Dung, N. H.; Enarson, D.; Falzon, D.; Granich, R. M.; Flanagan, K.; Flood, J.; Gandhi, N.; Garcia-Garcia, L.; Holtz, T. H.; Iseman, M.; Strand, M. J.; Jarlsberg, L. G.; Royce, S.; Keshavjee, S.; Kim, H. R.; Mitnick, C. D.; Lancaster, J.; Van Der Walt, M.; Lange, C.; Leimane, V.; Riekstina, V.; Leung, C. C.; Li, J.; Narita, M.; O'Riordan, P.; Palmero, D.; Park, S. K.; Pena, J.; Pérez-Guzmán, C.; Ponce-De-Leon, A.; Sifuentes-Osornio, J.; Quelapio, M. I D; Tupasi, T. E.; Robert, J.; Schaaf, H. S.; Seung, K. J.; Shin, S. S.; Shim, T. S.; Shiraishi, Y.; Sotgiu, G.; Tabarsi, P.; Vargas, M. H.; Westenhouse, J.; Yew, W. W.; Yim, J. J.

In: European Respiratory Journal, Vol. 49, No. 1, 1600993, 01.01.2017.

Research output: Contribution to journal › Article › peer-review

Fox, GJ, Benedetti, A, Cox, H, Koh, WJ, Viiklepp, P, Ahuja, S, Pasvol, G, Menzies, D, Ahuja, S, Ashkin, D, Avendaño, M, Banerjee, R, Bauer, M, Hollm-Delgado, MG, Pai, M, Shah, L, Bayona, JN, Becerra, M, Burgos, M, Centis, R, D'Ambrosio, L, Migliori, GB, Chan, ED, Chiang, CY, De Lange, WCM, Van Altena, R, Van Der Werf, TS, De Riemer, K, Dung, NH, Enarson, D, Falzon, D, Granich, RM, Flanagan, K, Flood, J, Gandhi, N, Garcia-Garcia, L, Holtz, TH, Iseman, M, Strand, MJ, Jarlsberg, LG, Royce, S, Keshavjee, S, Kim, HR, Mitnick, CD, Lancaster, J, Van Der Walt, M, Lange, C, Leimane, V, Riekstina, V, Leung, CC, Li, J, Narita, M, O'Riordan, P, Palmero, D, Park, SK, Pena, J, Pérez-Guzmán, C, Ponce-De-Leon, A, Sifuentes-Osornio, J, Quelapio, MID, Tupasi, TE, Robert, J, Schaaf, HS, Seung, KJ, Shin, SS, Shim, TS, Shiraishi, Y, Sotgiu, G, Tabarsi, P, Vargas, MH, Westenhouse, J, Yew, WW & Yim, JJ 2017, 'Group 5 drugs for multidrug-resistant tuberculosis: Individual patient data meta-analysis', European Respiratory Journal, vol. 49, no. 1, 1600993. https://doi.org/10.1183/13993003.00993-2016

Fox, Greg J. ; Benedetti, Andrea ; Cox, Helen ; Koh, Won Jung ; Viiklepp, Piret ; Ahuja, Shama ; Pasvol, Geoffrey ; Menzies, Dick ; Ahuja, S. ; Ashkin, D. ; Avendaño, M. ; Banerjee, R. ; Bauer, M. ; Hollm-Delgado, M. G. ; Pai, M. ; Shah, L. ; Bayona, J. N. ; Becerra, M. ; Burgos, M. ; Centis, R. ; D'Ambrosio, L. ; Migliori, G. B. ; Chan, E. D. ; Chiang, C. Y. ; De Lange, W. C M ; Van Altena, R. ; Van Der Werf, T. S. ; De Riemer, K. ; Dung, N. H. ; Enarson, D. ; Falzon, D. ; Granich, R. M. ; Flanagan, K. ; Flood, J. ; Gandhi, N. ; Garcia-Garcia, L. ; Holtz, T. H. ; Iseman, M. ; Strand, M. J. ; Jarlsberg, L. G. ; Royce, S. ; Keshavjee, S. ; Kim, H. R. ; Mitnick, C. D. ; Lancaster, J. ; Van Der Walt, M. ; Lange, C. ; Leimane, V. ; Riekstina, V. ; Leung, C. C. ; Li, J. ; Narita, M. ; O'Riordan, P. ; Palmero, D. ; Park, S. K. ; Pena, J. ; Pérez-Guzmán, C. ; Ponce-De-Leon, A. ; Sifuentes-Osornio, J. ; Quelapio, M. I D ; Tupasi, T. E. ; Robert, J. ; Schaaf, H. S. ; Seung, K. J. ; Shin, S. S. ; Shim, T. S. ; Shiraishi, Y. ; Sotgiu, G. ; Tabarsi, P. ; Vargas, M. H. ; Westenhouse, J. ; Yew, W. W. ; Yim, J. J. / Group 5 drugs for multidrug-resistant tuberculosis : Individual patient data meta-analysis. In: European Respiratory Journal. 2017 ; Vol. 49, No. 1.

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abstract = "The role of so-called {"}group 5{"} second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB. Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death. Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study. The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.",

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AU - Benedetti, Andrea

AU - Cox, Helen

AU - Koh, Won Jung

AU - Viiklepp, Piret

AU - Ahuja, Shama

AU - Pasvol, Geoffrey

AU - Menzies, Dick

AU - Ahuja, S.

AU - Ashkin, D.

AU - Avendaño, M.

AU - Banerjee, R.

AU - Bauer, M.

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AU - Shah, L.

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AU - D'Ambrosio, L.

AU - Migliori, G. B.

AU - Chan, E. D.

AU - Chiang, C. Y.

AU - De Lange, W. C M

AU - Van Altena, R.

AU - Van Der Werf, T. S.

AU - De Riemer, K.

AU - Dung, N. H.

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AU - Falzon, D.

AU - Granich, R. M.

AU - Flanagan, K.

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AU - Gandhi, N.

AU - Garcia-Garcia, L.

AU - Holtz, T. H.

AU - Iseman, M.

AU - Strand, M. J.

AU - Jarlsberg, L. G.

AU - Royce, S.

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AU - Kim, H. R.

AU - Mitnick, C. D.

AU - Lancaster, J.

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AU - Lange, C.

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AU - Riekstina, V.

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AU - Park, S. K.

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AU - Pérez-Guzmán, C.

AU - Ponce-De-Leon, A.

AU - Sifuentes-Osornio, J.

AU - Quelapio, M. I D

AU - Tupasi, T. E.

AU - Robert, J.

AU - Schaaf, H. S.

AU - Seung, K. J.

AU - Shin, S. S.

AU - Shim, T. S.

AU - Shiraishi, Y.

AU - Sotgiu, G.

AU - Tabarsi, P.

AU - Vargas, M. H.

AU - Westenhouse, J.

AU - Yew, W. W.

AU - Yim, J. J.

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AB - The role of so-called "group 5" second-line drugs as a part of antibiotic therapy for multidrug-resistant tuberculosis (MDR-TB) is widely debated. We performed an individual patient data meta-analysis to evaluate the effectiveness of several group 5 drugs including amoxicillin/clavulanic acid, thioacetazone, the macrolide antibiotics, linezolid, clofazimine and terizidone for treatment of patients with MDR-TB. Detailed individual patient data were obtained from 31 published cohort studies of MDR-TB therapy. Pooled treatment outcomes for each group 5 drug were calculated using a random effects meta-analysis. Primary analyses compared treatment success to a combined outcome of failure, relapse or death. Among 9282 included patients, 2191 received at least one group 5 drug. We found no improvement in treatment success among patients taking clofazimine, amoxicillin/clavulanic acid or macrolide antibiotics, despite applying a number of statistical approaches to control confounding. Thioacetazone was associated with increased treatment success (OR 2.6, 95% CI 1.1-6.1) when matched controls were selected from studies in which the group 5 drugs were not used at all, although this result was heavily influenced by a single study. The development of more effective antibiotics to treat drug-resistant TB remains an urgent priority.

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