TY - JOUR
T1 - Implications of multidrug resistance for the future of short-course chemotherapy of tuberculosis
T2 - a molecular study
AU - Heym, B.
AU - Honoré, N.
AU - Schurra, C.
AU - Cole, S. T.
AU - Heym, B.
AU - Truffot-Pernot, C.
AU - Grosset, J. H.
AU - Banerjee, A.
AU - Jacobs, W. R.
AU - van Embden, J. D.A.
PY - 1994/7/30
Y1 - 1994/7/30
N2 - 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.
AB - 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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U2 - 10.1016/S0140-6736(94)91338-2
DO - 10.1016/S0140-6736(94)91338-2
M3 - Article
C2 - 7914261
AN - SCOPUS:0028365052
SN - 0140-6736
VL - 344
SP - 293
EP - 298
JO - The Lancet
JF - The Lancet
IS - 8918
ER -