In vitro, ex-vivo and in vivo activities of ethambutol and sparfloxacin alone and in combination against mycobacteria

The MIC of ethambutol and sparfloxacin for Mycobacterium smegmatis and M. avium was determined using a broth dilution method. The MICs of sparfloxacin and ethambutol were lower for M. smegmatis than M. avium. The combination of ethambutol and sparfloxacin was additive against M. smegmatis but synergistic for M. avium. The effect of these drugs alone and in combination used at C(max) levels was screened against M. avium and M. tuberculosis H(37)Rv growing intracellularly in murine macrophage cell lines. In vivo studies using this combination given at 100 mg/kg of body weight once weekly showed greater activity than the drugs used singly. These results suggest that combination of ethambutol and sparfloxacin has significant activity intracellularly and in animal models against M. avium and M. tuberculosis.