Fluoroquinolone resistance in Mycobacterium tuberculosis: an assessment of MGIT 960, MODS and nitrate reductase assay and fluoroquinolone cross-resistance.

OBJECTIVES The aim of this study was to assess the sensitivity, specificity and time to results of mycobacterial growth indicator tube (MGIT) 960, microscopic observation drug susceptibility (MODS) assay and nitrate reductase assay (NRA) compared with the gold standard agar proportion method (PM), and to determine whether there is cross-resistance between older-generation fluoroquinolones and moxifloxacin. METHODS Mycobacterium tuberculosis isolates from culture-confirmed tuberculosis patients from 2002 to 2007 were tested for ofloxacin (2 mg/L) resistance by PM and MGIT 960. All isolates from 2005 and 2006 were also tested by MODS and NRA. Ofloxacin-resistant isolates by PM were further tested by all four methods using ciprofloxacin, levofloxacin and moxifloxacin. For each ofloxacin-resistant isolate, two ofloxacin-susceptible isolates were tested against all three fluoroquinolones using all four methods. RESULTS Of the 797 M. tuberculosis isolates, 19 (2.4%) were ofloxacin-resistant by PM. MGIT 960 had 100% sensitivity (95% CI, 83%-100%) and specificity (95% CI, 99.5%-100%). Of the 797 isolates, 239 were from 2005 to 2006 and 6 of these (2.5%) were resistant by PM. MODS had 100% sensitivity (95% CI, 61%-100%) and specificity (95% CI, 98%-100%). NRA had 100% sensitivity (95% CI, 61%-100%) and 98.7% specificity (95% CI, 96%-99.6%). The median time to results was shorter using MGIT 960 (8 days), MODS (6 days) or NRA (9 days) compared with PM (21 days) (P < 0.001). All 19 ofloxacin-resistant isolates were resistant to ciprofloxacin, levofloxacin and moxifloxacin by PM. CONCLUSIONS MGIT 960, MODS and NRA are sensitive and specific and more rapid than PM for identifying fluoroquinolone resistance in M. tuberculosis. Ofloxacin resistance was associated with cross-resistance to ciprofloxacin, levofloxacin and moxifloxacin.