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Free Content Determination of critical concentrations of second-line anti-tuberculosis drugs with clinical and microbiological relevance

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BACKGROUND: Reliable DST against second-line anti-tuberculosis drugs (SLDs) is crucial for the management of the increasing burden of patients affected by multidrug- and extensively drug-resistant TB.

METHODS: This study utilizes 252 clinical isolates of Mycobacterium tuberculosis from five countries (Hong Kong Special Administrative Region, Korea, Latvia, Peru, Philippines) with documented treatment histories to establish clinically and microbiologically relevant critical concentrations (CCs) of six SLDs for three routine testing methods: the absolute concentration method using Löwenstein-Jensen (LJ) medium, the 1% proportion method using Middlebrook 7H10 agar medium, and the radiometric BACTEC™ 460 system.

FINDINGS: In LJ medium, CCs of capreomycin, ethionamide, kanamycin, ofloxacin, ρ-aminosalicylic acid and cycloserine (CS) were respectively 40.0, 40.0, 30.0, 3.0, 1.0 and 30.0 mg/l. In 7H10 agar medium, the respective CCs for the first five antibiotics (except CS) were 8.0, 2.0–3.0, 3.0–5.0, 1.0–1.5 and 0.5–1.0 mg/l. In BACTEC 460 broth, the respective CCs were 1.5–2.0, 1.0–1.5, 2.0–3.0, 0.5–1.0 and 0.5–1.0 mg/l. Precautions in DST interpretation was also discussed.

INTERPRETATION: By adopting this set of CCs as a global standard to define second-line drug susceptibility and resistance, as well as precautions in result interpretation, the screening, diagnosis and management of patients with drug-resistant TB can be greatly improved.
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Keywords: critical concentration; second-line drugs; susceptibility testing; tuberculosis

Document Type: Regular Paper

Affiliations: 1: Tuberculosis Reference Laboratory, Hong Kong SAR, China 2: TB Laboratory, Massachusetts State Laboratory Institute, Boston, Massachusetts, USA 3: Partners in Health, Harvard Medical School, Boston, Massachusetts, USA 4: Stop TB Department, World Health Organization, Geneva, Switzerland 5: Stop TB Partnership, World Health Organization, Geneva, Switzerland 6: International Tuberculosis Research Center, Masan, Korea

Publication date: 01 March 2010

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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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