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

  • Author(s): 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
  • et al.
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]) u sing 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 secondline drug susceptibility testing (DST) as an indirect test was compared to MGITTMDST (n = 89). In the third (n = 30) and fourth (n = 156) phases, we determined the reproducibility and concordance of MODS secondline 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. © 2014 The Union.

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