Synergistic effect of two combinations of antituberculous drugs against Mycobacterium tuberculosis

Tuberculosis
Emma Rey-JuradoJulian González-Martín

Abstract

Fluoroquinolones such as ofloxacin are promising drugs to treat drug-resistant tuberculosis (TB) and have been proposed for shortening the treatment of TB. The objectives were to study the synergistic effect of the combinations of three drugs and to evaluate the in vitro interactions of the following combinations against Mycobacterium tuberculosis: A) isoniazid, rifampicin, and ethambutol and B) ofloxacin, rifampicin, and ethambutol using an adaptation of the two-dimensional chequerboard assay. A total of 12 isolates resistant to isoniazid or to isoniazid-streptomycin and 11 drug-susceptible isolates were tested. The fractional inhibitory concentration (FICI) was calculated as follows: FICI = FIC(A) + FICB + FIC(C) = A/MIC(A) + B/MIC(B) + C/MIC(C) where A, B and C were the MICs of each antibiotic in combination and MIC(A), MIC(B) and MIC(C) were the individual MICs. The FICI was interpreted as synergism when the value was ≤0.75. In combination A, 11 drug-susceptible isolates decreased the individual MIC one to three dilutions, showing indifferent activity in 81.8% (FICI = 0.88-1.6) and synergistic activity in 18.1% (FICI = 0.6). In combination B, 21 out of the 23 isolates studied (91.3%) showed synergism (FICI = 0.31-0.62). In ...Continue Reading

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Citations

Jan 15, 2013·International Journal of Antimicrobial Agents·Emma Rey-JuradoJulian González-Martín
Oct 1, 2015·International Journal of Antimicrobial Agents·Alexandre López-GavínJulian Gonzalez-Martín
Oct 3, 2013·Tuberculosis·Katiany R Caleffi-FerracioliRosilene F Cardoso
Jan 19, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elwira SieniawskaEwa Augustynowicz-Kopec
Sep 17, 2014·Antimicrobial Agents and Chemotherapy·Ana Requena-MéndezDavid A J Moore
Nov 10, 2018·The Journal of Antimicrobial Chemotherapy·Ana Requena-MéndezDavid A J Moore
Nov 23, 2019·European Journal of Medicinal Chemistry·Daniel SzulczykMarta Struga

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