Antibacterial activity of disulfiram and its metabolites

J Appl Microbiol. 2019 Jan;126(1):79-86. doi: 10.1111/jam.14094. Epub 2018 Oct 11.

Abstract

Aims: Disulfiram (Antabuse™) and its metabolites formed in vivo were evaluated as antibacterial agents against thirty species of Gram-positive and Gram-negative bacteria. The synergistic potential of disulfiram (DSF) and metabolite diethyldithiocarbamate (DDTC) with approved antibiotics were also compared by isobologram (checkerboard) analysis.

Methods and results: Standard microdilution susceptibility testing showed that most DSF metabolites did not possess appreciable antibacterial activity except for DDTC in Bacillus anthracis. Checkerboard studies revealed similarities between the combination drug effects of DSF and DDTC with standard antibiotics.

Conclusions: It was concluded from the susceptibility data that the metabolites would not extend the antibacterial spectrum of DSF in vivo. The data also suggest that the DDTC by-product of DSF metabolism potentiates the antibacterial activity of DSF as both a standalone and combination agent.

Significance and impact of the study: The study provides a greater understanding of the antibacterial effects of Antabuse and its metabolites. This research also demonstrates the potential application of DSF as an antibiotic adjuvant for the treatment of resistant staph infections.

Keywords: Bacillus; antibiotics; antimicrobials; disulfiram; metabolism; staphylococci.

MeSH terms

  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / metabolism
  • Anti-Bacterial Agents / pharmacology*
  • Disulfiram / chemistry
  • Disulfiram / metabolism
  • Disulfiram / pharmacology*
  • Ditiocarb / chemistry
  • Ditiocarb / metabolism
  • Ditiocarb / pharmacology*
  • Gram-Negative Bacteria / drug effects
  • Gram-Negative Bacteria / growth & development
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / growth & development

Substances

  • Anti-Bacterial Agents
  • Ditiocarb
  • Disulfiram