In vitro and in vivo antibacterial activity of pravibismane against Mycobacteroides abscessus.

The increasing prevalence of non-tuberculous mycobacterial lung infection represents a global challenge. Infections caused by Mycobacteroides abscessus commonly occur in individuals with underlying predisposing lung diseases such as cystic fibrosis (CF), non-CF-bronchiectasis, chronic obstructive pulmonary disease (COPD), and tuberculosis (TB). The unmet need in the treatment of M. abscessus pulmonary infection is driven by multidrug-resistance, ability to form biofilms, lengthy treatment, and drug-related side effects. Pravibismane was evaluated for its potential to reduce M. abscessus burden in vitro and in vivo. Pravibismane exhibited significantly lower (16- to 32-fold) minimum inhibitory concentrations (MICs) compared to amikacin. Treatment of THP-1 M. abscessus-infected macrophages with pravibismane led to a rapid reduction in intracellular M. abscessus while maintaining the viability of the THP-1 macrophages. Pravibismane demonstrated to be well-tolerated and efficacious in a chronic mouse M. abscessus lung infection model in which 28-day treatment with inhaled pravibismane substantially reduced the burden of M. abscessus in murine lung tissues. Overall, pravibismane exhibited promising efficacy by reducing intracellular M. abscessus levels in vitro and in a chronic mouse infection model. These preclinical results warrant investigation of pravibismane's ability to treat M. abscessus lung infection in relevant patient populations.