Department of Pharmaceutical Science and Research, School of Pharmacy, Marshall University, Huntington, WV, USA.
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, USA.
J Appl Microbiol. 2019 Jan;126(1):79-86. doi: 10.1111/jam.14094. Epub 2018 Oct 11.
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.
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.
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.
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.
评估体内形成的戒酒硫（安塔布司）及其代谢物作为抗革兰氏阳性和革兰氏阴性菌的 30 种抗生素。通过棋盘分析（棋盘）比较戒酒硫（DSF）及其代谢物二乙基二硫代氨基甲酸盐（DDTC）与批准抗生素的协同潜力。
标准微量稀释药敏试验表明，除炭疽芽孢杆菌中的 DDTC 外，大多数 DSF 代谢物没有明显的抗菌活性。棋盘研究表明，DSF 和 DDTC 与标准抗生素的联合药物作用具有相似性。
从药敏数据得出结论，代谢物不会在体内扩大 DSF 的抗菌谱。数据还表明，DDTC 是 DSF 代谢的副产物，增强了 DSF 作为独立和联合药物的抗菌活性。
该研究加深了对安塔布司及其代谢物的抗菌作用的理解。这项研究还表明，DSF 作为治疗耐药葡萄球菌感染的抗生素佐剂具有潜在的应用。
