In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis

Abstract

On 10% oleic acid-albumin-dextrose-catalase-enriched 7H11 agar medium, the MIC at which 90% of the isolates are inhibited for 20 strains of Mycobacterium tuberculosis was 0.5 microg of sparfloxacin (SPFX) or moxifloxacin (MXFX) per ml and 1.0 microg of clinafloxacin (CNFX) per ml, indicating that the in vitro activities of SPFX and MXFX were virtually identical and were slightly greater than that of CNFX. However, the in vivo activities of these drugs in a murine tuberculosis model differed considerably. Female Swiss mice were infected intravenously with 6.2 x 10(6) CFU of the H37Rv strain and treated for 4 weeks, beginning the next day after infection, with isoniazid (INH) serving as the positive control. By the criteria of 30-day survival rate, spleen weight, gross lung lesion, and mean number of CFU in the spleen, treatment with CNFX at up to 100 mg/kg of body weight six times weekly displayed no measurable effect against M. tuberculosis, whereas both SPFX and MXFX were effective; administration six times weekly of either of the latter two drugs demonstrated dosage-dependent bactericidal effects, as measured by enumeration of CFU in the spleens, and MXFX appeared more bactericidal than the same dosage of SPFX. Of the three fluoroquinolones, only MXFX at 100 mg/kg six times weekly appeared as bactericidal as INH at 25 mg/kg six times weekly. Thus, MXFX may be an important component of the newer combined regimens for treatment of tuberculosis.

FIG. 1

Survival rate of mice for 30 days after intravenous infection with 6.2 × 10⁶ CFU of M. tuberculosis H37Rv. By the time (day 1) the treatment began, there were 30 mice in each group. Drugs were given by gavage six times weekly, except for one group to which SPFX was given once weekly. The numbers after the abbreviations for the various drugs indicate the milligrams per kilogram per dose.

FIG. 2

Mean spleen weights for mice surviving at 30 days after intravenous infection with H37Rv. The control D1 bar represents the mean spleen weight for mice sacrificed the next day after infection. Error bars represent standard deviations. The numbers after the abbreviations for the various drugs indicate the milligrams per kilogram per dose.

FIG. 3

Mean numbers of CFU in the spleens of mice surviving at 30 days. Mice were infected intravenously with 6.2 × 10⁶ CFU of M. tuberculosis H37Rv, and treatment was begun the next day after infection. Error bars represent standard deviations. The numbers after abbreviations for the various drugs indicate the milligrams per kilogram per dose.