Clomiphene Citrate Shows Effective and Sustained Antimicrobial Activity against Mycobacterium abscessus

Int J Mol Sci. 2021 Oct 13;22(20):11029. doi: 10.3390/ijms222011029.

Abstract

Mycobacterium abscessus (M. abscessus) causes chronic pulmonary infections and is the most difficult non-tuberculous mycobacteria (NTM) to treat due to its resistance to current antimicrobial drugs, with a treatment success rate of 45.6%. Thus, novel treatment drugs are needed, of which we identified the drug clomiphene citrate (CC), known to treat infertility in women, to exhibit inhibitory activity against M. abscessus. To assess the potential of CC as a treatment for M. abscessus pulmonary diseases, we measured its efficacy in vitro and established the intracellular activity of CC against M. abscessus in human macrophages. CC significantly inhibited the growth of not only wild-type M. abscessus strains but also clinical isolate strains and clarithromycin (CLR)-resistant strains of M. abscessus. CC's drug efficacy did not have cytotoxicity in the infected macrophages. Furthermore, CC worked in anaerobic non-replicating conditions as well as in the presence of biofilm. The results of this in vitro study on M. abscessus activity suggest the possibility of using CC to develop new drug hypotheses for the treatment of M. abscessus infections.

Keywords: Mycobacterium abscessus; clomiphene citrate; drug repurposing; drug resistance; non-tuberculosis mycobacteria.

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Anti-Bacterial Agents / therapeutic use
  • Clomiphene / pharmacology*
  • Clomiphene / therapeutic use
  • Drug Repositioning
  • Humans
  • Macrophages*
  • Mycobacterium Infections, Nontuberculous / drug therapy*
  • Mycobacterium abscessus / drug effects*
  • THP-1 Cells

Substances

  • Anti-Bacterial Agents
  • Clomiphene