Microscopic-observation drug-susceptibility assay for the diagnosis of TB

David A.J. Moore, Carlton A.W. Evans, Robert H. Gilman, Luz Caviedes, Jorge Coronel, Aldo Vivar, Eduardo Sanchez, Yvette Piñedo, Juan Carlos Saravia, Cayo Salazar, Richard Oberhelman, Maria Graciela Hollm-Delgado, Doris LaChira, A. Roderick Escombe, Jon S. Friedland

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Abstract

BACKGROUND: New diagnostic tools are urgently needed to interrupt the transmission of tuberculosis and multidrug-resistant tuberculosis. Rapid, sensitive detection of tuberculosis and multidrug-resistant tuberculosis in sputum has been demonstrated in proof-of-principle studies of the microscopic-observation drug-susceptibility (MODS) assay, in which broth cultures are examined microscopically to detect characteristic growth. METHODS: In an operational setting in Peru, we investigated the performance of the MODS assay for culture and drug-susceptibility testing in three target groups: unselected patients with suspected tuberculosis, prescreened patients at high risk for tuberculosis or multidrug-resistant tuberculosis, and unselected hospitalized patients infected with the human immunodeficiency virus. We compared the MODS assay head-tohead with two reference methods: automated mycobacterial culture and culture on Löwenstein-Jensen medium with the proportion method. RESULTS: Of 3760 sputum samples, 401 (10.7%) yielded cultures positive for Mycobacterium tuberculosis. Sensitivity of detection was 97.8% for MODS culture, 89.0% for automated mycobacterial culture, and 84.0% for Löwenstein-Jensen culture (P<0.001); the median time to culture positivity was 7 days, 13 days, and 26 days, respectively (P<0.001), and the median time to the results of susceptibility tests was 7 days, 22 days, and 68 days, respectively. The incremental benefit of a second MODS culture was minimal, particularly in patients at high risk for tuberculosis or multidrug-resistant tuberculosis. Agreement between MODS and the reference standard for susceptibility was 100% for rifampin, 97% for isoniazid, 99% for rifampin and isoniazid (combined results for multidrug resistance), 95% for ethambutol, and 92% for streptomycin (kappa values, 1.0, 0.89, 0.93, 0.71, and 0.72, respectively). CONCLUSIONS: A single MODS culture of a sputum sample offers more rapid and sensitive detection of tuberculosis and multidrug-resistant tuberculosis than the existing gold-standard methods used.

Original languageEnglish (US)
Pages (from-to)1539-1550
Number of pages12
JournalNew England Journal of Medicine
Volume355
Issue number15
DOIs
StatePublished - Oct 12 2006

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ASJC Scopus subject areas

  • Medicine(all)

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Moore, D. A. J., Evans, C. A. W., Gilman, R. H., Caviedes, L., Coronel, J., Vivar, A., Sanchez, E., Piñedo, Y., Saravia, J. C., Salazar, C., Oberhelman, R., Hollm-Delgado, M. G., LaChira, D., Escombe, A. R., & Friedland, J. S. (2006). Microscopic-observation drug-susceptibility assay for the diagnosis of TB. New England Journal of Medicine, 355(15), 1539-1550. https://doi.org/10.1056/NEJMoa055524