Date of Award

2023

Degree Name

Pharmaceutical Sciences

College

School of Pharmacy

Type of Degree

M.S.

Document Type

Thesis

First Advisor

Dr. Timothy Long, Committee Chairperson

Second Advisor

Dr. Jeremy McAleer, Committee Member

Third Advisor

Dr. Michael Hambuchen, Committee Member

Abstract

Disulfiram (Antabuse®) is an oral prescription drug used to treat alcohol abuse disorder (AUD). Disulfiram (DSF) and its metabolites act on the body by inhibiting multiple enzymes involved in alcohol metabolism. This study aims to understand the pharmacology of disulfiram as an antibacterial medication. Previous studies on DSF showed antibiotic activity against multidrug-resistant Staphylococcus aureus strains (MRSA). The initial aim of this study was to decipher the mechanisms involved in inhibiting bacterial growth by DSF, which was done by performing biochemical studies. The studies revealed that DSF had antagonistic effects on redox buffering and energy production. Another aim of this study was to evaluate the in vitro pharmacodynamics of DSF in combination with vancomycin (VAN) against S. aureus strains with intermediate levels of susceptibility. The data showed that DSF had synergistic potential with VAN, significantly antagonizing the growth of S. aureus when combined. Overall, this study established that DSF has significant antibacterial activity against S. aureus individually. Moreover, it could be used as an antibiotic adjuvant with VAN against several S. aureus strains with intermediate levels of VAN susceptibility.

Subject(s)

Antibiotics – Research.

Disulfiram – Research.

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