Clofazimine inhalation suspension for the aerosol treatment of pulmonary nontuberculous mycobacterial infections

Brandon Banaschewski, Deepshikha Verma, Lian J. Pennings, Matthew Zimmerman, Qihua Ye, Jake Gadawa, Veronique Dartois, Diane Ordway, Jakko van Ingen, Stefan Ufer, Kevin Stapleton, Thomas Hofmann

Research output: Contribution to journalArticlepeer-review

35 Scopus citations


Background: Nontuberculous mycobacteria are recognized as a concern for cystic fibrosis (CF) patients due to increasing disease prevalence and the potential for detrimental effects on pulmonary function and mortality. Current standard of care involves prolonged systemic antibiotics, which often leads to severe side effects and poor treatment outcomes. In this study, we investigated the tolerability and efficacy of a novel inhaled therapeutic in various mouse models of NTM disease. Methods: We developed clofazimine inhalation suspension (CIS), a novel formulation of clofazimine developed for inhaled administration. To determine the efficacy, minimum inhibitory concentrations were evaluated in vitro, and tolerability of CIS was determined in naïve mouse models over various durations. After establishing tolerability, CIS efficacy was tested in in vivo infection models of both Mycobacterium avium and M. abscessus. Lung and plasma clofazimine levels after chronic treatments were evaluated. Results: Clofazimine inhalation suspension demonstrated antimycobacterial activity in vitro, with MIC values between 0.125 and 2 μg/ml for M. avium complex and M. abscessus. Administration into naïve mice showed that CIS was well tolerated at doses up to 28 mg/kg over 28 consecutive treatments. In vivo, CIS was shown to significantly improve bacterial elimination from the lungs of both acute and chronic NTM-infected mouse models compared to negative controls and oral clofazimine administration. Clofazimine concentrations in lung tissue were approximately four times higher than the concentrations achieved by oral dosing. Conclusion: Clofazimine inhalation suspension is a well tolerated and effective novel therapeutic candidate for the treatment of NTM infections in mouse models.

Original languageEnglish (US)
Pages (from-to)714-720
Number of pages7
JournalJournal of Cystic Fibrosis
Issue number5
StatePublished - Sep 2019

All Science Journal Classification (ASJC) codes

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine


  • Clofazimine
  • Cystic fibrosis
  • Inhalation
  • Nontuberculous mycobacteria


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