Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study

doi:10.1016/S0140-6736(94)91338-2

The Lancet

Volume 344, Issue 8918, 30 July 1994, Pages 293-298

https://doi.org/10.1016/S0140-6736(94)91338-2 Get rights and content

Abstract

Summary

Tuberculosis-control programmes are compromised by the increased frequency of multidrug-resistant strains of Mycobacterium tuberculosis. We used the polymerase chain reaction (PCR) and single-strand conformation polymorphism (SSCP) analysis techniques to establish the molecular basis of resistance in 37 drug-resistant isolates of M tuberculosis, and correlated these findings with clinical and antibiotic-sensitivity data.

Resistance to isoniazid was found in 36 strains, 16 of which were also resistant to ethionamide. Of the 36 isoniazid- resistant strains, 23 had mutations in the katG gene, and 5 of these also had mutations in the inhA gene. A further 5 strains had alterations in the inhA locus without the katG gene being mutated. Rifampicin resistance was less frequent (13 strains) and usually associated with isoniazid resistance (11 of 13 strains). Mutations in the rpoB gene were detected for all these rifampicin-resistant isolates. Mutations in the rpsL and rrs genes, associated with streptomycin resistance, were found in 13 of 25 and 2 of 25 streptomycin-resistant strains, respectively. The same chromosomal mutations, or combinations of mutations, were found in strains displaying single or multidrug resistance, from cases of both primary and secondary resistance, and from patients infected with human immunodeficiency virus.

Thus, multidrug resistance is not dur to a novel machanism and tuberculosis chemotherapy is not subject to a new threat. Lancet1994; 344: 293–98

See Editorial page 277

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ArticlesImplications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study

Abstract

Tuberculosis in patients with immunodeficiency virus infection

N Engl J Med

Tuberculosis: commentary on a reemergent killer

Science

The new tuberculosis

N Engl J Med

The emergence of drug-resistant tuberculosis in New York City

N Engl J Med

Treatment of multidrug-resistant tuberculosis

N Engl J Med

Resurgent tuberculosis in New York city: human immunodeficiency virus, homelessness, and the decline of tuberculosis control programs

Am Rev Respir Dis

Nosocomial transmission of multidrug-resistant tuberculosis among HIV-infected persons-Florida and New York; 1988-1991

MMWR

Nosocomial transmission of tuberculosis in a hospital unit for HIV-infected patients

JAMA

The catalase-peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis

Nature

inhA, a gene encoding a target for isoniazid and ethionamide in Mycobacterium tuberculosis

Science

Detection of rifampicin- resistance mutations in Mycobacterium tuberculosis

Lancet

Streptomycin resistance in mycobacteria

Antimicrob Agents Chemother

Molecular basis of streptomycin resistance in Mycobacterium tuberculosis: alterations of the ribosomal protein S12 gene and point mutations within a functional 16S ribosomal RNA pseudoknot

Mol Microbiol

The rpsL gene and streptomycin resistance in single and multiple drug-resistant strains of Mycobacterium tuberculosis

Mol Microbiol

Articles
Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis: a molecular study