Genotypic assessment of isoniazid and rifampin resistance in Mycobacterium tuberculosis: a blind study at reference laboratory level

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Journal of Clinical Microbiology, Mar 1997, 719-723, Vol 35, No. 3
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Genotypic assessment of isoniazid and rifampin resistance in Mycobacterium tuberculosis: a blind study at reference laboratory level

A Telenti, N Honore, C Bernasconi, J March, A Ortega, B Heym, HE Takiff and ST Cole
Institut fur Medizinische Mikrobiologie, Universitat Bern, Switzerland. telenti@imm.unibe.ch

Progress in understanding the basis of resistance to isoniazid (INH) and rifampin (RMP) has allowed molecular tests for the detection of drug-resistant tuberculosis to be developed. Consecutive isolates (n = 95) of Mycobacterium tuberculosis, from a Spanish reference laboratory investigating outbreaks of multidrug-resistant tuberculosis, were coded and sent to two external laboratories for genotypic analysis of INH and RMP resistance by PCR-single-strand conformation polymorphism (SSCP) analysis of specific regions of four genes: part of the coding sequence of katG and the promoter regions of inhA and ahpC for INH and the RMP resistance region of rpoB. After correction for the presence of outbreak strains and multiple isolates from single patients, RMP resistance was detected successfully by PCR-SSCP in > 96% of the RMP- resistant strains. PCR-SSCP had a sensitivity of 87% for INH resistance detection, and mutations in katG, inhA, katG-inhA, ahpC, and katG-ahpC were identified in 36.8, 31.6, 2.6, 13.2, and 2.6%, respectively, of the unique strains. Specificity was 100%. Molecular detection of resistance to the two main antituberculous drugs, INH and RMP, can be accomplished accurately by using a strategy which limits analysis to four genetic regions. This may allow the expedient analysis of drug resistance by reference laboratories.

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Torres, M. J., Criado, A., Palomares, J. C., Aznar, J. (2000). Use of Real-Time PCR and Fluorimetry for Rapid Detection of Rifampin and Isoniazid Resistance-Associated Mutations in Mycobacterium tuberculosis. J. Clin. Microbiol. 38: 3194-3199 [Abstract] [Full Text]
Valim, A. R. M., Rossetti, M. L. R., Ribeiro, M. O., Zaha, A. (2000). Mutations in the rpoB Gene of Multidrug-Resistant Mycobacterium tuberculosis Isolates from Brazil. J. Clin. Microbiol. 38: 3119-3122 [Abstract] [Full Text]
Vilchèze, C., Morbidoni, H. R., Weisbrod, T. R., Iwamoto, H., Kuo, M., Sacchettini, J. C., Jacobs, W. R. Jr. (2000). Inactivation of the inhA-Encoded Fatty Acid Synthase II (FASII) Enoyl-Acyl Carrier Protein Reductase Induces Accumulation of the FASI End Products and Cell Lysis of Mycobacterium smegmatis. J. Bacteriol. 182: 4059-4067 [Abstract] [Full Text]
Piatek, A. S., Telenti, A., Murray, M. R., El-Hajj, H., Jacobs, W. R. Jr., Kramer, F. R., Alland, D. (2000). Genotypic Analysis of Mycobacterium tuberculosis in Two Distinct Populations Using Molecular Beacons: Implications for Rapid Susceptibility Testing. Antimicrob. Agents Chemother. 44: 103-110 [Abstract] [Full Text]
Scarpellini, P., Braglia, S., Carrera, P., Cedri, M., Cichero, P., Colombo, A., Crucianelli, R., Gori, A., Ferrari, M., Lazzarin, A. (1999). Detection of Rifampin Resistance in Mycobacterium tuberculosis by Double Gradient-Denaturing Gradient Gel Electrophoresis. Antimicrob. Agents Chemother. 43: 2550-2554 [Abstract] [Full Text]
Lee, A. S. G., Lim, I. H. K., Tang, L. L. H., Telenti, A., Wong, S. Y. (1999). Contribution of kasA Analysis to Detection of Isoniazid-Resistant Mycobacterium tuberculosis in Singapore. Antimicrob. Agents Chemother. 43: 2087-2089 [Abstract] [Full Text]
Rozwarski, D. A., Vilcheze, C., Sugantino, M., Bittman, R., Sacchettini, J. C. (1999). Crystal Structure of the Mycobacterium tuberculosis Enoyl-ACP Reductase, InhA, in Complex with NAD+ and a C16 Fatty Acyl Substrate. J. Biol. Chem. 274: 15582-15589 [Abstract] [Full Text]
Riska, P. F., Su, Y., Bardarov, S., Freundlich, L., Sarkis, G., Hatfull, G., Carrière, C., Kumar, V., Chan, J., Jacobs, W. R. Jr. (1999). Rapid Film-Based Determination of Antibiotic Susceptibilities of Mycobacterium tuberculosis Strains by Using a Luciferase Reporter Phage and the Bronx Box. J. Clin. Microbiol. 37: 1144-1149 [Abstract] [Full Text]
Cockerill, F. R. III (1999). Genetic Methods for Assessing Antimicrobial Resistance. Antimicrob. Agents Chemother. 43: 199-212 [Full Text]
Marttila, H. J., Soini, H., Eerola, E., Vyshnevskaya, E., Vyshnevskiy, B. I., Otten, T. F., Vasilyef, A. V., Viljanen, M. K. (1998). A Ser315Thr Substitution in KatG Is Predominant in Genetically Heterogeneous Multidrug-Resistant Mycobacterium tuberculosis Isolates Originating from the St. Petersburg Area in Russia. Antimicrob. Agents Chemother. 42: 2443-2445 [Abstract] [Full Text]
Telenti, A (1998). Genetics and pulmonary medicine bullet �5: Genetics of drug resistant tuberculosis. Thorax 53: 793-797 [Full Text]
Watterson, S. A., Wilson, S. M., Yates, M. D., Drobniewski, F. A. (1998). Comparison of Three Molecular Assays for Rapid Detection of Rifampin Resistance in Mycobacterium tuberculosis. J. Clin. Microbiol. 36: 1969-1973 [Abstract] [Full Text]
Miesel, L., Weisbrod, T. R., Marcinkeviciene, J. A., Bittman, R., Jacobs, W. R. Jr. (1998). NADH Dehydrogenase Defects Confer Isoniazid Resistance and Conditional Lethality in Mycobacterium smegmatis. J. Bacteriol. 180: 2459-2467 [Abstract] [Full Text]
Rozwarski, D. A., Grant, G. A., Barton, D. H., Jacobs Jr., W. R., Sacchettini, J. C. (1998). Modification of the NADH of the Isoniazid Target (InhA) from Mycobacterium tuberculosis. Science 279: 98-102 [Abstract] [Full Text]

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