Center for Health Policy and Research (CHPR) Publications


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

UMMS Affiliation

Massachusetts Supranational TB Reference Laboratory; Center for Health Policy and Research

Publication Date


Document Type



Antitubercular Agents; Extensively Drug-Resistant Tuberculosis; therapy; Humans; Microbial Sensitivity Tests; Mycobacterium tuberculosis; Tuberculosis, Multidrug-Resistant


Health Services Administration | Health Services Research | Public Health


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 Lowenstein-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, rho-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.


Int J Tuberc Lung Dis. 2010 Mar;14(3):282-8. Link to article on publisher's website

Journal/Book/Conference Title

The international journal of tuberculosis and lung disease : the official journal of the International Union against Tuberculosis and Lung Disease

Related Resources

Link to Article in PubMed