Antibacterial activity of disulfiram and its metabolites

• Published in: Journal of applied microbiology Vol. 126; no. 1; pp. 79 - 86
• Main Authors: Frazier, K.R., Moore, J.A., Long, T.E.
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01-01-2019
• Subjects: Antibacterial activity; Antibacterial agents; Antibiotics; antimicrobials; Bacillus; Data processing; Disulfiram; Gram-negative bacteria; In vivo methods and tests; Metabolism; Metabolites; staphylococci; staphylococci; disulfiram; metabolism; antimicrobials; antibiotics; Bacillus
• ISSN: 1364-5072; 1365-2672
• DOI: 10.1111/jam.14094

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.