Activity of clofazimine against clinical isolates of Mycobacterium tuberculosis with different spectrum of drug resistance to anti-tuberculosis drugs

Due to the widespread drug resistance of M. tuberculosis (MTB), it is necessary to assess the possibility of using drugs with antimycobacterial activity previously used in other pathologies, e.g. clofazimine, in anti-tuberculosis chemotherapy regimens. The aim was to determine the phenotypic sensitivity to clofazimine of clinical strains of MTB with different spectrum of drug resistance. Methods . Clofazimine sensitivity was studied for 75 MTB clinical strains by serial microdilutions in Middlebrook 7H9 liquid medium (50 were drug-susceptible, 25 have MDR and pre-XDR), with estimation of MIC50, MIC90 and epidemiologic cut-off value of MIC (ECOFF). Results . The growth of most MTB strains (76%) was suppressed by clofazimine concentrations ranging from 0.06 to 0.125 μg/ml. The growth of 50% (MIC50) and 90% (MIC90) of drug-sensitive strains was inhibited by clofazimine concentrations of 0.125 and 0.25 μg/ml, respectively, while the growth of drug-resistant strains was inhibited by 0.125 and 0.5 μg/ml, respectively. The ECOFF value was 0.25 μg/ml. Conclusion . Clofazimine even in low concentrations inhibits the growth of MTB clinical strains regardless of sensitivity to other antimycobacterial drugs. The obtained data serve as an additional basis for the use of clofazimine in the complex treatment of tuberculosis, including MDR and XDR pathogens.