Polymorphisms associated with resistance and cross-resistance to aminoglycosides and capreomycin in Mycobacterium tuberculosis isolates from south Korean patients with drug-resistant tuberculosis

Laura E. Via, Sang Nae Cho, Soohee Hwang, Hyeeun Bang, Seung Kyu Park, Hyung Seok Kang, Doosoo Jeon, Seon Yeong Min, Taegwon Oh, Yeun Kim, Young Mi Kim, Vignesh Rajan, Sharon Y. Wong, Isdore Chola Shamputa, Matthew Carroll, Lisa Goldfeder, Song A. Lee, Steven M. Holland, Seokyong Eum, Hyeyoung LeeClifton E. Barry

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Abstract

The aminoglycosides streptomycin, amikacin, and kanamycin and the cyclic polypeptide capreomycin are all widely used in second-line therapy for patients who develop multidrug-resistant tuberculosis. We have characterized a set of 106 clinical isolates of Mycobacterium tuberculosis using phenotypic drug susceptibility testing (DST) to determine the extent of resistance to each agent and cross-resistance between agents. These results were compared with polymorphisms in the DNA sequences of ribosome-associated genes previously implicated in resistance and with the clinical outcomes of subjects from whom these isolates were obtained. Thirty-six (34%) of these isolates displayed resistance to one or more of these agents, and the majority of these (20 of 36) showed cross-resistance to one or more agents. Most (33 of 36) of the resistant isolates showed polymorphisms in the 16S ribosome components RpsL and rrs. Three resistant strains (3 of 36) were identified that had no known polymorphisms in ribosomal constituents. For kanamycin and streptomycin, molecular DST significantly outperformed phenotypic DST using the absolute concentration method for predicting 4-month sputum conversion (likelihood ratios of 4.0 and 2.0, respectively) and was equivalent to phenotypic DST using the National Committee for Clinical Laboratory Standards (NCCLS)-approved agar proportion method for estimating MIC (likelihood ratio, 4.0). These results offer insight into mechanisms of resistance and crossresistance among these agents and suggest that the development of rapid molecular tests to distinguish polymorphisms would significantly enhance clinical utility of this important class of second-line antituberculosis drugs.

Original languageEnglish
Pages (from-to)402-411
Number of pages10
JournalJournal of Clinical Microbiology
Volume48
Issue number2
DOIs
Publication statusPublished - 2010 Feb

All Science Journal Classification (ASJC) codes

  • Microbiology (medical)

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    Via, L. E., Cho, S. N., Hwang, S., Bang, H., Park, S. K., Kang, H. S., Jeon, D., Min, S. Y., Oh, T., Kim, Y., Kim, Y. M., Rajan, V., Wong, S. Y., Shamputa, I. C., Carroll, M., Goldfeder, L., Lee, S. A., Holland, S. M., Eum, S., ... Barry, C. E. (2010). Polymorphisms associated with resistance and cross-resistance to aminoglycosides and capreomycin in Mycobacterium tuberculosis isolates from south Korean patients with drug-resistant tuberculosis. Journal of Clinical Microbiology, 48(2), 402-411. https://doi.org/10.1128/JCM.01476-09