Which aminoglycoside or fluoroquinolone is more active against Mycobacterium tuberculosis in mice?

Abstract

To identify the most active aminoglycoside or fluoroquinolone for the treatment of tuberculosis, the in vivo activities of four different aminoglycosides and three different fluoroquinolones were compared with that of isoniazid (INH) in a murine tuberculosis model. Mice were each inoculated intravenously with 2.3 x 10(7) CFU of Mycobacterium tuberculosis H37Rv. Treatment began the next day (D1) after inoculation and continued for 4 weeks, at the frequency of six times weekly with one of the following regimens: INH, 25 mg/kg; ofloxacin, 200 mg/kg; levofloxacin, 100 or 200 mg/kg; sparfloxacin (SPFX), 50 mg/kg; and streptomycin, kanamycin, amikacin (AMIKA), and isepamicin, all at 200 mg/kg. The dosages of the treatments were presumably equivalent to their clinically tolerated dosages. The severity of infection and effectiveness of the treatment were assessed by the survival rate, spleen weights, gross lung lesions, and the numbers of CFU in the spleens. The results indicate that INH is more bactericidal than any of the aminoglycosides or fluoroquinolones tested, that AMIKA is the most active aminoglycoside, and that SPFX at 50 mg/kg is far more bactericidal than the treatment with other fluoroquinolones.