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, Martie 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, M. Van Der Walt, T. S. Van Der Werf, M. H. Vargas, P. Viiklepp, J. Westenhouse, W. W. Yew, J. J. Yim

Research output: Contribution to journalArticle

83 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1364-1374
Number of pages11
JournalClinical Infectious Diseases
Volume59
Issue number10
DOIs
StatePublished - Nov 15 2014
Externally publishedYes

Fingerprint

Extensively Drug-Resistant Tuberculosis
Meta-Analysis
Pyrazinamide
Pharmaceutical Preparations
Ethambutol
Multidrug-Resistant Tuberculosis
Tuberculosis
Therapeutics
Fluoroquinolones
Drug Resistance

Keywords

  • Drug susceptibility test
  • Meta-analysis
  • Multidrug resistant
  • Treatment outcomes
  • Tuberculosis

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

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

In: Clinical Infectious Diseases, Vol. 59, No. 10, 15.11.2014, p. 1364-1374.

Research output: Contribution to journalArticle

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 Walt, M, 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, Mayara L. ; Hussain, Hamidah ; Weyer, Karin ; Garcia-Garcia, Lourdes ; Leimane, Vaira ; Leung, Chi Chiu ; Narita, Masahiro ; Penã, Jose M. ; Ponce-De-Leon, Alfredo ; Seung, Kwonjune J. ; Shean, Karen ; Sifuentes-Osornio, José ; Van Der Walt, Martie ; Van Der Werf, Tjip S. ; Yew, Wing Wai ; Menzies, Dick ; Ahuja, S. D. ; Ashkin, D. ; Avendano, M. ; Banerjee, R. ; Bauer, M. ; Bayona, J. N. ; Becerra, M. C. ; Benedetti, A. ; Burgos, M. ; Centis, R. ; Chan, E. D. ; Chiang, C. Y. ; Cox, H. ; D'Ambrosio, L. ; Deriemer, K. ; Dung, N. H. ; Enarson, D. ; Falzon, D. ; Flanagan, K. ; Flood, J. ; Garcia-Garcia, M. L. ; Gandhi, N. ; Granich, R. M. ; Hollm-Delgado, M. G. ; Holtz, T. H. ; Iseman, M. D. ; Jarlsberg, L. G. ; Keshavjee, S. ; Kim, H. R. ; Koh, W. J. ; Lancaster, J. ; Lange, C. ; De Lange, W. C M ; Leimane, V. ; Leung, C. C. ; Li, J. ; Menzies, D. ; Migliori, G. B. ; Mishustin, S. P. ; Mitnick, C. D. ; Narita, M. ; O'Riordan, P. ; Pai, M. ; Palmero, D. ; Park, S. K. ; Pasvol, G. ; Pena, J. ; Pérez-Guzmán, C. ; Quelapio, M. I D ; Ponce-De-leon, A. ; Riekstina, V. ; Robert, J. ; Royce, S. ; Schaaf, H. S. ; Seung, K. J. ; Shah, L. ; Shim, T. S. ; Shin, S. S. ; Shiraishi, Y. ; Sifuentes-Osornio, J. ; Sotgiu, G. ; Strand, M. J. ; Tabarsi, P. ; Tupasi, T. E. ; Van Altena, R. ; Van Der Walt, M. ; Van Der Werf, T. S. ; Vargas, M. H. ; Viiklepp, P. ; Westenhouse, J. ; Yew, W. W. ; Yim, J. J. / 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. In: Clinical Infectious Diseases. 2014 ; Vol. 59, No. 10. pp. 1364-1374.
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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.",
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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, Martie

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 Walt, M.

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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UR - http://www.scopus.com/inward/citedby.url?scp=84918817893&partnerID=8YFLogxK

U2 - 10.1093/cid/ciu619

DO - 10.1093/cid/ciu619

M3 - Article

C2 - 25097082

AN - SCOPUS:84918817893

VL - 59

SP - 1364

EP - 1374

JO - Clinical Infectious Diseases

JF - Clinical Infectious Diseases

SN - 1058-4838

IS - 10

ER -