Effects of clofazimine on planktonic and biofilm growth of Mycobacterium tuberculosis and Mycobacterium smegmatis.

Mycobacteria form lipid-rich biofilms that restrict the efficacy of antimicrobial chemotherapy, possibly necessitating the use of lipophilic antibiotics. In the current study, the activity of one such agent, clofazimine, against Mycobacterium tuberculosis and Mycobacterium smegmatis planktonic cells and biofilms was investigated. Minimum inhibitory concentrations (MICs) of clofazimine were determined for planktonic cultures, whilst minimum bactericidal concentrations (MBCs) were determined for planktonic, biofilm-producing and biofilm-encased organisms using standard bacteriological procedures. The effects of clofazimine on biofilm formation and the stability of pre-formed biofilm were measured using a crystal violet-based spectrophotometric procedure. In the case of M. smegmatis, clofazimine was found to be active against planktonic phase (MICs and MBCs of 2.5mg/L and >20mg/L, respectively) and biofilm-producing organisms (MBC of 2.5mg/L); clofazimine demonstrated greater activity against M. tuberculosis, corresponding values of 0.06, 5 and 0.3mg/L. Although clofazimine inhibited biofilm production both by M. tuberculosis and M. smegmatis (P<0.05 at ≥0.07mg/L and ≥0.3mg/L, respectively) and appeared to reduce the pre-formed M. tuberculosis biofilm, addition of antimicrobial agent to pre-existing biofilm matrices failed to kill biofilm-encased organisms. In conclusion, clofazimine is more effective against M. tuberculosis than against M. smegmatis, exhibiting bactericidal activity both for actively growing and slowly replicating bacilli but not for non-replicating organisms of both species.

Inhaled microparticles containing clofazimine are efficacious in treatment of experimental tuberculosis in mice.

Inhalable clofazimine-containing dry powder microparticles (CFM-DPI) and native clofazimine (CFM) were evaluated for activity against Mycobacterium tuberculosis in human monocyte-derived macrophage cultures and in mice infected with a low-dose aerosol. Both formulations resulted in 99% killing at 2.5 µg/ml in vitro. In mice, 480 µg and 720 µg CFM-DPI inhaled twice per week over 4 weeks reduced numbers of CFU in the lung by as much as log(10) 2.6; 500 µg oral CFM achieved a log(10) 0.7 reduction.

Clofazimine: current status and future prospects.

Clofazimine, a lipophilic riminophenazine antibiotic, possesses both antimycobacterial and anti-inflammatory activities. However, its efficacy has been demonstrated only in the treatment of leprosy, not in human tuberculosis, despite the fact that this agent is impressively active in vitro against multidrug-resistant strains of Mycobacterium tuberculosis. Recent insights into novel targets and mechanisms of antimicrobial and anti-inflammatory activity coupled with the acquisition of innovative drug delivery technologies have, however, rekindled interest in clofazimine as a potential therapy for multidrug- and extensively multidrug-resistant tuberculosis in particular, as well as several autoimmune diseases. The primary objective of this review is to critically evaluate these recent developments and to assess their potential impact on improving the therapeutic efficacy and versatility of clofazimine.