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

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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.

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

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Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Microbiology (medical)

Cite this

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