Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the MODS assay.


Trollip, AP; Moore, D; Coronel, J; Caviedes, L; Klages, S; Victor, T; Romancenco, E; Crudu, V; Ajbani, K; Vineet, VP; Rodrigues, C; Jackson, RL; Eisenach, K; Garfein, RS; Rodwell, TC; Desmond, E; Groessl, EJ; Ganiats, TG; Catanzaro, A; (2014) Second-line drug susceptibility breakpoints for Mycobacterium tuberculosis using the MODS assay. The international journal of tuberculosis and lung disease, 18 (2). pp. 227-32. ISSN 1027-3719 DOI: https://doi.org/10.5588/ijtld.13.0229

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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.

Item Type: Article
Faculty and Department: Faculty of Infectious and Tropical Diseases > Dept of Clinical Research
Research Centre: HIV Research Group
TB Centre
PubMed ID: 24429318
Web of Science ID: 330155500018
URI: http://researchonline.lshtm.ac.uk/id/eprint/1472187

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