Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the MODS assay
Abstract:OBJECTIVE: To establish breakpoint concentrations for the fluoroquinolones (moxifloxacin [MFX] and ofloxacin [OFX]) and injectable second-line drugs (amikacin [AMK], kanamycin [KM] and capreomycin [CPM]) using the microscopic observation drug susceptibility (MODS) assay.
SETTING: A multinational study conducted between February 2011 and August 2012 in Peru, India, Moldova and South Africa.
DESIGN: In the first phase, breakpoints for the fluoroquinolones and injectable second-line drugs (n = 58) were determined. In the second phase, MODS second-line drug susceptibility testing (DST) as an indirect test was compared to MGIT™ DST (n = 89). In the third (n = 30) and fourth (n = 156) phases, we determined the reproducibility and concordance of MODS second-line DST directly from sputum.
RESULTS: Breakpoints for MFX (0.5 μg/ml), OFX (1 μg/ml), AMK (2 μg/ml), KM (5 μg/ml) and CPM (2.5 μg/ml) were determined. In all phases, MODS results were highly concordant with MGIT DST. The few discrepancies suggest that the MODS breakpoint concentrations for some drugs may be too low.
CONCLUSION: MODS second-line DST yielded comparable results to MGIT second-line DST, and is thus a promising alternative. Further studies are needed to confirm the accuracy of the drug breakpoints and the reliability of MODS second-line DST as a direct test.
Document Type: Research Article
Affiliations: 1: Biomedical Sciences, Department of Science and Technology/National Research Foundation Centre of Excellence for Biomedical Tuberculosis Research, Medical Research Council Centre for Molecular and Cellular Biology, Stellenbosch University, Cape Town, South Africa 2: TB Centre and Department of Clinical Research, London School of Hygiene & Tropical Medicine, London, UK; Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru 3: Laboratorio de Investigación de Enfermedades Infecciosas, Universidad Peruana Cayetano Heredia, Lima, Peru 4: Microbiology and Morphology Laboratory, Phthisiopneumology Institute, Chisinau, Moldova 5: Department of Microbiology, Parmanand Deepchand Hinduja National Hospital and Medical Research Centre Tertiary Care Hospital, Mumbai, India 6: University of California San Diego School of Medicine, La Jolla, California, USA 7: Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA 8: Division of Global Public Health, University of California San Diego School of Medicine, La Jolla, California, USA 9: Mycobacteriology and Mycology Section, Microbial Diseases Laboratory, California Department of Public Health, Richmond, California, USA 10: University of California San Diego, Veterans' Affairs San Diego Healthcare System, La Jolla, California, USA 11: University of California San Diego Health Services Research Center, UCSD, La Jolla, California, USA
Publication date: February 1, 2014
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.
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