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Free Content Association of streptomycin resistance mutations with level of drug resistance and Mycobacterium tuberculosis genotypes

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OBJECTIVES: To determine 1) the relationship between specific streptomycin (SM) resistance mutations and the minimum inhibitory concentration (MIC), and 2) whether these mutations are preferentially associated with the Beijing genotype in Viet Nam.

METHODS: A total of 131 consecutive Mycobacterium tuberculosis isolates resistant to either isoniazid (INH) or rifampicin (RMP), collected previously, were tested for SM resistance, spoligotyped and sequenced in the rpsL, rrs and gidB genes. The MIC for 50 mutants was also determined.

RESULTS: Overall, 116/131 isolates were SM-resistant. The three most frequently occurring mutation sites in rpsL and rrs were at codon 43 of rpsL (72/116, 62.1%), rpsL88 (22/116, 18.9%) and rrs514 (8/116, 6.9%). Mutations in the rrs910 region were found in two isolates (1.7%), and three isolates had mutations in both rpsL and rrs (2.6%). gidB mutations were found in both resistant and susceptible strains. Among SM-resistant isolates resistant to INH/RMP, the Beijing genotype was strongly associated with rpsL43 mutation (aOR 23.6, 95%CI 2.9–193.4, P = 0.002). The median MIC for each mutation was as follows: rpsL43 = 256 μg/ml, rpsL88 = 16 μg/ml, 515 loop = 4 μg/ml, 910 region = 8 μg/ml, and double mutation = 256 μg/ml. We found a strong association between rpsL43 and high drug resistance levels, with all rpsL43 mutants having an MIC >256 μg/ml (P < 0.001).
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Keywords: Beijing genotype; drug resistance; streptomycin; tuberculosis

Document Type: Research Article

Affiliations: 1: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam 2: Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases, Ho Chi Minh City, Viet Nam 3: Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam 4: Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Viet Nam; Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Oxford, UK

Publication date: 01 April 2012

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  • The International Journal of Tuberculosis and Lung Disease publishes articles on all aspects of lung health, including public health-related issues such as training programmes, cost-benefit analysis, legislation, epidemiology, intervention studies and health systems research. The IJTLD is dedicated to the continuing education of physicians and health personnel and the dissemination of information on tuberculosis and lung health world-wide.

    Certain IJTLD articles are selected for translation into French, Spanish, Chinese or Russian. They are available on the Union website

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