Determination of critical concentrations of second-line anti-tuberculosis drugs with clinical and microbiological relevance
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.
Document Type: Regular Paper
Tuberculosis Reference Laboratory, Hong Kong SAR, China
TB Laboratory, Massachusetts State Laboratory Institute, Boston, Massachusetts, USA
Partners in Health, Harvard Medical School, Boston, Massachusetts, USA
Stop TB Department, World Health Organization, Geneva, Switzerland
Stop TB Partnership, World Health Organization, Geneva, Switzerland
International Tuberculosis Research Center, Masan, Korea
Publication date: March 1, 2010
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