Combinatory activity of linezolid and levofloxacin with antituberculosis drugs in Mycobacterium tuberculosis.

Setting: The increase of multidrug and extensively drug resistant Mycobacterium tuberculosis strains turns the search for new tuberculosis (TB) treatment options of paramount importance.

Objective: In this sense, the present study evaluates the in vitro activity of isoniazid (INH)/rifampicin (RIF)/levofloxacin (LVX) and INH/RIF/linezolid (LNZ) combinations in resistant M. tuberculosis.

Design: The activities of the combinations were evaluated with M. tuberculosis HRv, susceptible and 10 resistant clinical isolates by three-dimensional checkerboard. LVX and LNZ were used as the third drug at fixed ½ and ¼ minimum inhibitory concentration (MIC). INH and RIF were tested at concentrations ranging from 0.0009 μg/mL to 50 μg/mL and 0.0009 μg/mL to 800 μg/mL, respectively. The combinatorial effects were determined by the Fractional Inhibitory Concentration Index (FICI). FICI values ≤ 0.75, 0.75-4 and ≥4 were considered as synergism, indifferent and antagonism, respectively.

Results: MIC ranged from 0.03 - 6.25 μg/mL for INH, 0.008-100 μg/mL for RIF, 0.12-0.25 μg/mL for LVX and 0.25-0.5 μg/mL for LNZ in the HRv and all clinical isolates. INH/RIF/LVX and INH/RIF/LNZ synergisms were observed in 40 and 50% of the resistant M. tuberculosis clinical isolates and better observed for INH and RIF combined to LVX or LNZ at ¼ MIC.

Conclusion: The present study calls attention for the potential use of INH/RIF/LVX and INH/RIF/LNZ combinations in the treatment of resistant TB.