Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis

Mayara L. Bastos; Hamidah Hussain; Karin Weyer; Lourdes Garcia-Garcia; Vaira Leimane; Chi Chiu Leung; Masahiro Narita; Jose M. Penã; Alfredo Ponce-De-Leon; Kwonjune J. Seung; Karen Shean; José Sifuentes-Osornio; M. Van Der Walt; Tjip S. Van Der Werf; Wing Wai Yew; Dick Menzies; S. D. Ahuja; D. Ashkin; M. Avendano; R. Banerjee; M. Bauer; J. N. Bayona; M. C. Becerra; A. Benedetti; M. Burgos; R. Centis; E. D. Chan; C. Y. Chiang; H. Cox; L. D'Ambrosio; K. Deriemer; N. H. Dung; D. Enarson; D. Falzon; K. Flanagan; J. Flood; M. L. Garcia-Garcia; N. Gandhi; R. M. Granich; M. G. Hollm-Delgado; T. H. Holtz; M. D. Iseman; L. G. Jarlsberg; S. Keshavjee; H. R. Kim; W. J. Koh; J. Lancaster; C. Lange; W. C M De Lange; V. Leimane; C. C. Leung; J. Li; D. Menzies; G. B. Migliori; S. P. Mishustin; C. D. Mitnick; M. Narita; P. O'Riordan; M. Pai; D. Palmero; S. K. Park; G. Pasvol; J. Pena; C. Pérez-Guzmán; M. I D Quelapio; A. Ponce-De-leon; V. Riekstina; J. Robert; S. Royce; H. S. Schaaf; K. J. Seung; L. Shah; T. S. Shim; S. S. Shin; Y. Shiraishi; J. Sifuentes-Osornio; G. Sotgiu; M. J. Strand; P. Tabarsi; T. E. Tupasi; R. Van Altena; T. S. Van Der Werf; M. H. Vargas; P. Viiklepp; J. Westenhouse; W. W. Yew; J. J. Yim

doi:10.1093/cid/ciu619

Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis

Mayara L. Bastos, Hamidah Hussain, Karin Weyer, Lourdes Garcia-Garcia, Vaira Leimane, Chi Chiu Leung, Masahiro Narita, Jose M. Penã, Alfredo Ponce-De-Leon, Kwonjune J. Seung, Karen Shean, José Sifuentes-Osornio, M. Van Der Walt, Tjip S. Van Der Werf, Wing Wai Yew, Dick Menzies, S. D. Ahuja, D. Ashkin, M. Avendano, R. BanerjeeM. Bauer, J. N. Bayona, M. C. Becerra, A. Benedetti, M. Burgos, R. Centis, E. D. Chan, C. Y. Chiang, H. Cox, L. D'Ambrosio, K. Deriemer, N. H. Dung, D. Enarson, D. Falzon, K. Flanagan, J. Flood, M. L. Garcia-Garcia, N. Gandhi, R. M. Granich, M. G. Hollm-Delgado, T. H. Holtz, M. D. Iseman, L. G. Jarlsberg, S. Keshavjee, H. R. Kim, W. J. Koh, J. Lancaster, C. Lange, W. C M De Lange, V. Leimane, C. C. Leung, J. Li, D. Menzies, G. B. Migliori, S. P. Mishustin, C. D. Mitnick, M. Narita, P. O'Riordan, M. Pai, D. Palmero, S. K. Park, G. Pasvol, J. Pena, C. Pérez-Guzmán, M. I D Quelapio, A. Ponce-De-leon, V. Riekstina, J. Robert, S. Royce, H. S. Schaaf, K. J. Seung, L. Shah, T. S. Shim, S. S. Shin, Y. Shiraishi, J. Sifuentes-Osornio, G. Sotgiu, M. J. Strand, P. Tabarsi, T. E. Tupasi, R. Van Altena, T. S. Van Der Werf, M. H. Vargas, P. Viiklepp, J. Westenhouse, W. W. Yew, J. J. Yim

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

96 Scopus citations

Abstract

Background: Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drugresistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis.

Methods: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis.We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center.

Results: DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for secondline injectables and fluoroquinolones, odds ranged from 2.4 to 4.6.

Conclusions: DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.

Original language	English (US)
Pages (from-to)	1364-1374
Number of pages	11
Journal	Clinical Infectious Diseases
Volume	59
Issue number	10
DOIs	https://doi.org/10.1093/cid/ciu619
State	Published - Nov 15 2014
Externally published	Yes

Keywords

Drug susceptibility test
Meta-analysis
Multidrug resistant
Treatment outcomes
Tuberculosis

ASJC Scopus subject areas

Infectious Diseases
Microbiology (medical)

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Bastos, M. L., Hussain, H., Weyer, K., Garcia-Garcia, L., Leimane, V., Leung, C. C., Narita, M., Penã, J. M., Ponce-De-Leon, A., Seung, K. J., Shean, K., Sifuentes-Osornio, J., Van Der Walt, M., Van Der Werf, T. S., Yew, W. W., Menzies, D., Ahuja, S. D., Ashkin, D., Avendano, M., ... Yim, J. J. (2014). Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis. Clinical Infectious Diseases, 59(10), 1364-1374. https://doi.org/10.1093/cid/ciu619

Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis. / Bastos, Mayara L.; Hussain, Hamidah; Weyer, Karin et al.
In: Clinical Infectious Diseases, Vol. 59, No. 10, 15.11.2014, p. 1364-1374.

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

Bastos, ML, Hussain, H, Weyer, K, Garcia-Garcia, L, Leimane, V, Leung, CC, Narita, M, Penã, JM, Ponce-De-Leon, A, Seung, KJ, Shean, K, Sifuentes-Osornio, J, Van Der Walt, M, Van Der Werf, TS, Yew, WW, Menzies, D, Ahuja, SD, Ashkin, D, Avendano, M, Banerjee, R, Bauer, M, Bayona, JN, Becerra, MC, Benedetti, A, Burgos, M, Centis, R, Chan, ED, Chiang, CY, Cox, H, D'Ambrosio, L, Deriemer, K, Dung, NH, Enarson, D, Falzon, D, Flanagan, K, Flood, J, Garcia-Garcia, ML, Gandhi, N, Granich, RM, Hollm-Delgado, MG, Holtz, TH, Iseman, MD, Jarlsberg, LG, Keshavjee, S, Kim, HR, Koh, WJ, Lancaster, J, Lange, C, De Lange, WCM, Leimane, V, Leung, CC, Li, J, Menzies, D, Migliori, GB, Mishustin, SP, Mitnick, CD, Narita, M, O'Riordan, P, Pai, M, Palmero, D, Park, SK, Pasvol, G, Pena, J, Pérez-Guzmán, C, Quelapio, MID, Ponce-De-leon, A, Riekstina, V, Robert, J, Royce, S, Schaaf, HS, Seung, KJ, Shah, L, Shim, TS, Shin, SS, Shiraishi, Y, Sifuentes-Osornio, J, Sotgiu, G, Strand, MJ, Tabarsi, P, Tupasi, TE, Van Altena, R, Van Der Werf, TS, Vargas, MH, Viiklepp, P, Westenhouse, J, Yew, WW & Yim, JJ 2014, 'Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis', Clinical Infectious Diseases, vol. 59, no. 10, pp. 1364-1374. https://doi.org/10.1093/cid/ciu619

Bastos ML, Hussain H, Weyer K, Garcia-Garcia L, Leimane V, Leung CC et al. Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis. Clinical Infectious Diseases. 2014 Nov 15;59(10):1364-1374. doi: 10.1093/cid/ciu619

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title = "Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis",

abstract = "Background: Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drugresistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis.Methods: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis.We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center.Results: DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for secondline injectables and fluoroquinolones, odds ranged from 2.4 to 4.6.Conclusions: DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.",

keywords = "Drug susceptibility test, Meta-analysis, Multidrug resistant, Treatment outcomes, Tuberculosis",

author = "Bastos, {Mayara L.} and Hamidah Hussain and Karin Weyer and Lourdes Garcia-Garcia and Vaira Leimane and Leung, {Chi Chiu} and Masahiro Narita and Pen{\~a}, {Jose M.} and Alfredo Ponce-De-Leon and Seung, {Kwonjune J.} and Karen Shean and Jos{\'e} Sifuentes-Osornio and {Van Der Walt}, M. and {Van Der Werf}, {Tjip S.} and Yew, {Wing Wai} and Dick Menzies and Ahuja, {S. D.} and D. Ashkin and M. Avendano and R. Banerjee and M. Bauer and Bayona, {J. N.} and Becerra, {M. C.} and A. Benedetti and M. Burgos and R. Centis and Chan, {E. D.} and Chiang, {C. Y.} and H. Cox and L. D'Ambrosio and K. Deriemer and Dung, {N. H.} and D. Enarson and D. Falzon and K. Flanagan and J. Flood and Garcia-Garcia, {M. L.} and N. Gandhi and Granich, {R. M.} and Hollm-Delgado, {M. G.} and Holtz, {T. H.} and Iseman, {M. D.} and Jarlsberg, {L. G.} and S. Keshavjee and Kim, {H. R.} and Koh, {W. J.} and J. Lancaster and C. Lange and {De Lange}, {W. C M} and V. Leimane and Leung, {C. C.} and J. Li and D. Menzies and Migliori, {G. B.} and Mishustin, {S. P.} and Mitnick, {C. D.} and M. Narita and P. O'Riordan and M. Pai and D. Palmero and Park, {S. K.} and G. Pasvol and J. Pena and C. P{\'e}rez-Guzm{\'a}n and Quelapio, {M. I D} and A. Ponce-De-leon and V. Riekstina and J. Robert and S. Royce and Schaaf, {H. S.} and Seung, {K. J.} and L. Shah and Shim, {T. S.} and Shin, {S. S.} and Y. Shiraishi and J. Sifuentes-Osornio and G. Sotgiu and Strand, {M. J.} and P. Tabarsi and Tupasi, {T. E.} and {Van Altena}, R. and {Van Der Werf}, {T. S.} and Vargas, {M. H.} and P. Viiklepp and J. Westenhouse and Yew, {W. W.} and Yim, {J. J.}",

year = "2014",

month = nov,

day = "15",

doi = "10.1093/cid/ciu619",

language = "English (US)",

volume = "59",

pages = "1364--1374",

journal = "Clinical Infectious Diseases",

issn = "1058-4838",

publisher = "Oxford University Press",

number = "10",

}

TY - JOUR

T1 - Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs

T2 - An individual patient data meta-analysis

AU - Bastos, Mayara L.

AU - Hussain, Hamidah

AU - Weyer, Karin

AU - Garcia-Garcia, Lourdes

AU - Leimane, Vaira

AU - Leung, Chi Chiu

AU - Narita, Masahiro

AU - Penã, Jose M.

AU - Ponce-De-Leon, Alfredo

AU - Seung, Kwonjune J.

AU - Shean, Karen

AU - Sifuentes-Osornio, José

AU - Van Der Walt, M.

AU - Van Der Werf, Tjip S.

AU - Yew, Wing Wai

AU - Menzies, Dick

AU - Ahuja, S. D.

AU - Ashkin, D.

AU - Avendano, M.

AU - Banerjee, R.

AU - Bauer, M.

AU - Bayona, J. N.

AU - Becerra, M. C.

AU - Benedetti, A.

AU - Burgos, M.

AU - Centis, R.

AU - Chan, E. D.

AU - Chiang, C. Y.

AU - Cox, H.

AU - D'Ambrosio, L.

AU - Deriemer, K.

AU - Dung, N. H.

AU - Enarson, D.

AU - Falzon, D.

AU - Flanagan, K.

AU - Flood, J.

AU - Garcia-Garcia, M. L.

AU - Gandhi, N.

AU - Granich, R. M.

AU - Hollm-Delgado, M. G.

AU - Holtz, T. H.

AU - Iseman, M. D.

AU - Jarlsberg, L. G.

AU - Keshavjee, S.

AU - Kim, H. R.

AU - Koh, W. J.

AU - Lancaster, J.

AU - Lange, C.

AU - De Lange, W. C M

AU - Leimane, V.

AU - Leung, C. C.

AU - Li, J.

AU - Menzies, D.

AU - Migliori, G. B.

AU - Mishustin, S. P.

AU - Mitnick, C. D.

AU - Narita, M.

AU - O'Riordan, P.

AU - Pai, M.

AU - Palmero, D.

AU - Park, S. K.

AU - Pasvol, G.

AU - Pena, J.

AU - Pérez-Guzmán, C.

AU - Quelapio, M. I D

AU - Ponce-De-leon, A.

AU - Riekstina, V.

AU - Robert, J.

AU - Royce, S.

AU - Schaaf, H. S.

AU - Seung, K. J.

AU - Shah, L.

AU - Shim, T. S.

AU - Shin, S. S.

AU - Shiraishi, Y.

AU - Sifuentes-Osornio, J.

AU - Sotgiu, G.

AU - Strand, M. J.

AU - Tabarsi, P.

AU - Tupasi, T. E.

AU - Van Altena, R.

AU - Van Der Werf, T. S.

AU - Vargas, M. H.

AU - Viiklepp, P.

AU - Westenhouse, J.

AU - Yew, W. W.

AU - Yim, J. J.

PY - 2014/11/15

Y1 - 2014/11/15

N2 - Background: Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drugresistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis.Methods: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis.We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center.Results: DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for secondline injectables and fluoroquinolones, odds ranged from 2.4 to 4.6.Conclusions: DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.

AB - Background: Individualized treatment for multidrug-resistant (MDR) tuberculosis and extensively drugresistant (XDR) tuberculosis depends upon reliable and valid drug susceptibility testing (DST) for pyrazinamide, ethambutol, and second-line tuberculosis drugs. However, the reliability of these tests is uncertain, due to unresolved methodological issues. We estimated the association of DST results for pyrazinamide, ethambutol, and second-line drugs with treatment outcomes in patients with MDR tuberculosis and XDR tuberculosis.Methods: We conducted an analysis of individual patient data assembled from 31 previously published cohort studies of patients with MDR and XDR tuberculosis.We used data on patients' clinical characteristics including DST results, treatment received, outcomes, and laboratory methods in each center.Results: DST methods and treatment regimens used in different centers varied considerably. Among 8955 analyzed patients, in vitro susceptibility to individual drugs was consistently and significantly associated with higher odds of treatment success (compared with resistance to the drug), if that drug was used in the treatment regimen. Various adjusted and sensitivity analyses suggest that this was not explained by confounding. The adjusted odds of treatment success for ethambutol, pyrazinamide, and the group 4 drugs ranged from 1.7 to 2.3, whereas for secondline injectables and fluoroquinolones, odds ranged from 2.4 to 4.6.Conclusions: DST for ethambutol, pyrazinamide, and second-line tuberculosis drugs appears to provide clinically useful information to guide selection of treatment regimens for MDR and XDR tuberculosis.

KW - Drug susceptibility test

KW - Meta-analysis

KW - Multidrug resistant

KW - Treatment outcomes

KW - Tuberculosis

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U2 - 10.1093/cid/ciu619

DO - 10.1093/cid/ciu619

M3 - Article

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AN - SCOPUS:84918817893

SN - 1058-4838

VL - 59

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EP - 1374

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

IS - 10

ER -

Treatment outcomes of patients with multidrug-resistant and extensively drug-resistant tuberculosis according to drug susceptibility testing to first- and second-line drugs: An individual patient data meta-analysis

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