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.

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.

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.

Dry-powder pulmonary insufflation in the mouse for application to vaccine or drug studies.

Pulmonary delivery of substances in small animal models is often useful for experimental testing of various vaccine and drug candidates. One of the most challenging elements to such protocols is the efficient disposition of test materials in the lungs of mice. Herein we detail a means to deliver dry powders of an inhalant live-attenuated Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine against Mycobacterium tuberculosis to the lungs of mice.

Immunization by a bacterial aerosol.

By manufacturing a single-particle system in two particulate forms (i.e., micrometer size and nanometer size), we have designed a bacterial vaccine form that exhibits improved efficacy of immunization.

Drying a tuberculosis vaccine without freezing.

With the increasing incidence of tuberculosis and drug resistant disease in developing countries due to HIV/AIDS, there is a need for vaccines that are more effective than the present bacillus Calmette-Guérin (BCG) vaccine. We demonstrate that BCG vaccine can be dried without traditional freezing and maintained with remarkable refrigerated and room-temperature stability for months through spray drying. Studies with a model Mycobacterium (Mycobacterium smegmatis) revealed that by removing salts and cryoprotectant (e.