Tuberculosis (Edinburgh, Scotland) · 2018
Combinatory activity of linezolid and levofloxacin with antituberculosis drugs in Mycobacterium tuberculosis.
Сравнительное исследованиеСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Santos Nathally Claudiane de Souza, Scodro Regiane Bertin de Lima, de Almeida Aryadne Larissa, Baldin Vanessa Pietrowski, Nakamura de Vasconcelos Sandra Sayuri, Siqueira Vera Lucia Dias, Caleffi-Ferracioli Katiany Rizzieri, Campanerut-Sá Paula Aline Zanetti, Cardoso Rosilene Fressatti
Аннотация
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 H37Rv, 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 H37Rv 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.
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 H37Rv, 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 H37Rv 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.