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Free Content Wild-type distributions of seven oral second-line drugs against Mycobacterium tuberculosis

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OBJECTIVES: To determine wild-type minimum inhibitory concentration (MIC) distributions for Mycobacterium tuberculosis, as the background data for defining susceptibility breakpoints are limited.

METHODS: We determined wild-type MIC distributions of M. tuberculosis using a 96-stick replicator in Middlebrook 7H10 (7H10) medium for ethionamide (ETH), prothionamide, thiacetazone, cycloserine, rifabutin (RFB), clofazimine and linezolid in consecutive susceptible clinical isolates (n = 78).

RESULTS: Tentative epidemiological wild-type cut-offs (ECOFF) were determined for all investigated drugs where World Health Organization recommended critical concentrations for 7H10 are lacking, except for ETH. As the ECOFF was closely related to the non-wild-type strains for ETH and thiacetazone, the use of an intermediary (I) category in drug susceptibility testing could increase reproducibility. The cross-resistance between ETH and isoniazid was 21%. Applying 0.5 mg/l as a breakpoint for RFB classified two non-wild type and rpoB mutated isolates as susceptible for RFB and resistant against rifampicin.

CONCLUSIONS: We propose that wild-type MIC distributions should be used as a tool to define clinical breakpoints against second-line drugs. This is increasingly important considering the rapid emergence of drug resistance.

Keywords: MIC susceptibility testing; ethionamide; linezolid; pharmacokinetics; second-line drugs

Document Type: Regular Paper


Affiliations: 1: Department of Clinical Microbiology, Kalmar County Hospital, Kalmar, Sweden 2: Department of Bacteriology, Swedish Institute of Disease Control (SMI), Stockholm, Sweden 3: Department of Clinical Microbiology, Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden 4: Medical Microbiology, Department of Laboratory Medicine, Lund University, Malmö, Sweden 5: Department of Clinical Microbiology, Växjö Hospital, Växjö, Sweden; and Department of Medical Sciences, Uppsala University, Uppsala, Sweden

Publication date: April 1, 2011

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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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