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Free Content Phenotypic and genotypic diversity in a multinational sample of drug-resistant Mycobacterium tuberculosis isolates

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OBJECTIVE: To develop and evaluate rapid, molecular-based drug susceptibility testing (DST) for extensively drug-resistant tuberculosis (XDR-TB), we assembled a phenotypically and genotypically diverse collection of Mycobacterium tuberculosis isolates from patients evaluated for drug resistance in four high-burden countries.

METHODS: M. tuberculosis isolates from India (n = 111), Moldova (n = 90), the Philippines (n = 96), and South Africa (n = 103) were selected from existing regional and national repositories to maximize phenotypic diversity for resistance to isoniazid, rifampin (RMP), moxifloxacin, ofloxacin, amikacin, kanamycin, and capreomycin. MGIT™ 960 was performed on viable isolates in one laboratory using standardized procedures and drug concentrations. Genetic diversity within drug resistance phenotypes was assessed.

RESULTS: Nineteen distinct phenotypes were observed among 400 isolates with complete DST results. Diversity was greatest in the Philippines (14 phenotypes), and least in South Africa (9 phenotypes). Nearly all phenotypes included multiple genotypes. All sites provided isolates resistant to injectables but susceptible to fluoroquinolones. Many patients were taking drugs to which their disease was resistant.

DISCUSSION: Diverse phenotypes for XDR-TB-defining drugs, including resistance to fluoroquinolones and/or injectable drugs in RMP-susceptible isolates, indicate that RMP susceptibility does not ensure effectiveness of a standard four-drug regimen. Rapid, low-cost DST assays for first- and second-line drugs are thus needed.
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Keywords: diagnostics; drug susceptibility testing; epidemiology; genotype; repository

Document Type: Research Article

Affiliations: 1: Department of Medicine, University of California, San Diego, California, USA 2: University of Arkansas, Department of Biological Sciences, Fayetteville, Arkansas, USA 3: Department of Family Medicine and Public Health, University of California, San Diego, California, USA 4: Tropical Disease Foundation, Inc, Philippine Institute of Tuberculosis Building, Makati City, Philippines 5: Hinduja National Hospital, Mumbai, India 6: Microbiology and Morphology Laboratory, Institute of Phthisiopneumology, Chisinau, Moldova 7: California Department of Public Health, Richmond, California, USA 8: Department of Biomedical Sciences, Stellenbosch University, Cape Town, South Africa 9: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA 10: Department of Microbiology, University of Hawaii, Honolulu, Hawaii, USA

Publication date: April 1, 2015

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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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