Rapid in vivo screening of experimental drugs for tuberculosis using gamma interferon gene-disrupted mice

Abstract

We have developed a rapid new in vivo method for screening experimental drugs for their activity against Mycobacterium tuberculosis by using the gamma interferon gene-disrupted (GKO) C57BL/6 mouse. Due to the rapid growth of the infection, statistical differences indicating positive efficacy of active compounds can be seen after only 8 days of treatment. To validate this model, several fluoroquinolones, including ciprofloxacin, levofloxacin, moxifloxacin, and gatifloxacin, were tested in parallel.

FIG. 1.

Numbers of viable M. tuberculosis organisms in lungs (A) and spleens (B) of infected mice after once-daily treatment with fluoroquinolones at 100 (•), 200 (□), and 400 mg/kg (▪) or INH at 25 mg/kg (○) for 8 treatment days. Infected untreated mice from control groups (⊡) were sacrificed at the start and end of the treatment period. The results are means ± standard deviations of data from five mice per group. Results were statistically significant relative to results for the untreated controls for levofloxacin, moxifloxacin, gatifloxacin, and INH in spleens and lungs for all concentrations tested (P < 0.01); ciprofloxacin showed a statistically significant result only in spleen at 400 mg/kg (P < 0.01).