Evaluation of Disulfiram Drug Combinations and Identification of Other More Effective Combinations Against Stationary Phase

Overview

Journal Antibiotics (Basel)

Specialty Pharmacology

Date 2020 Aug 30

PMID 32858987

Citations 8

Authors

Hector S Alvarez-Manzo

Yumin Zhang

Wanliang Shi

Ying Zhang

Affiliations

Soon will be listed here.

Abstract

Lyme disease, caused by , is the most common vector-borne disease in USA, and 10-20% of patients will develop persistent symptoms despite treatment ("post-treatment Lyme disease syndrome"). persisters, which are not killed by the current antibiotics for Lyme disease, are considered one possible cause. Disulfiram has shown to be active against , but its activity against persistent forms is not well characterized. We assessed disulfiram as single drug and in combinations against stationary-phase culture enriched with persisters. Disulfiram was not very effective in the drug exposure experiment (survival rate (SR) 46.3%) or in combinations. Clarithromycin (SR 41.1%) and nitroxoline (SR 37.5%) were equally effective when compared to the current Lyme antibiotic cefuroxime (SR 36.8%) and more active than disulfiram. Cefuroxime + clarithromycin (SR 25.9%) and cefuroxime + nitroxoline (SR 27.5%) were significantly more active than cefuroxime + disulfiram (SR 41.7%). When replacing disulfiram with clarithromycin or nitroxoline in three-drug combinations, bacterial viability decreased significantly and subculture studies showed that combinations with these two drugs (cefuroxime + clarithromycin/nitroxoline + furazolidone/nitazoxanide) inhibited the regrowth, while disulfiram combinations did not (cefuroxime + disulfiram + furazolidone/nitazoxanide). Thus, clarithromycin and nitroxoline should be further assessed to determine their role as potential treatment alternatives in the future.

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