Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the 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.
Keywords: MODS; aminoglycosides; drug susceptibility testing; fluoroquinolones; tuberculosis
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: 01 February 2014
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