In vitro and in vivo activities of sparfloxacin (AT-4140) against Mycobacterium tuberculosis

Ji, B.; Truffot-Pernot, C.; Grosset, J.

Tubercle 72(3): 181-186


ISSN/ISBN: 0041-3879
PMID: 1663283
DOI: 10.1016/0041-3879(91)90004-c
Accession: 040388524

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The in vitro and in vivo activities of sparfloxacin (AT-4140) against M. tuberculosis are reported. The MICs of sparfloxacin for 50% and 90% of 18 clinical isolates were, respectively, 0.25 and 0.5 mg/l, one or two dilutions lower than that of ciprofloxacin and ofloxacin. In mice infected intravenously with 0.1 mg M. tuberculosis H37Rv strain, the minimal effective dosage of sparfloxacin, as assessed by survival rate, spleen enlargement and gross lung lesions, was 12.5 mg/kg. The activities of various regimens were in the following rank order: INH 25 mg/kg = sparfloxacin 50-100 mg/kg greater than ofloxacin 300 mg/kg greater than (or =) sparfloxacin 25 mg/kg greater than sparfloxacin 12.5 mg/kg greater than (or =) ofloxacin 200 mg/kg greater than ofloxacin 100 mg/kg greater than (or =) negative control. Therefore, on a weight to weight basis, sparfloxacin was six to eight-fold more active against M. tuberculosis infection in mice than ofloxacin. In addition, WIN 57273, a new broad-spectrum fluoroquinolone, at a dosage of 100 mg/kg daily, was inactive against M. tuberculosis infection.