[A study on the activity of clofazimine with antituberculous drugs against Mycobacterium tuberculosis]

To explore the role of clofazimine in combination with other antituberculous drugs against Mycobacterium tuberculosis.

The minimal inhibitory concentration (MIC) of each drug and the drugs in combination against M. tuberculosis H₃₇Rv were determined, and the synergetic activities according to the fractional inhibitory concentration (FIC) formula was calculated. Female BALB/C mice were infected intravenously with 0.2 mg/L portions containing 5 × 10⁵ CFU of the MDR clinical isolate 2931. One day after the infection, 6 mice were sacrificed and the numbers of CFU in the lungs and spleens were determined. The remaining mice were allocated either to untreated group or to drug-treated groups (6 mice per group). Thirty days post-infection, both untreated and treated mice were sacrificed and the CFU counted.

Clofazimine in combination with the 10 antituberculosis drugs resulted in two- to eight fold reduction in MIC. The FIC of clofazimine (Cfz) in combination with p-aminosalicylic acid (PAS), protionamide (Pto), clarithromycin (Clr), and capreomycin were less than 0.5, suggesting a synergic interaction against M. tuberculosis H₃₇Rv. All the drug treatments reduced the numbers of CFU in the lungs and spleens compared with the numbers in the untreated controls. Of the individual drugs, Cfz was the most effective on day 30, with a mean CFU count decrease of 1.82 and 2.32 lg₁₀, in comparison with that of the untreated control. The Cfz-Clr (clarithromycin) combination showed significantly greater activity than the control or Clr alone, with a mean CFU count decrease of 1.30 and 1.91 lg, in comparison with that of the Clr treatment. Cfz-Clr was slightly more active than Cfz alone, but not at a statistically significant level.

The activity of clofazimine was enhanced by the addition of clarithromycin. These observations are important for the therapy of multidrug-resistant tuberculosis.