Graduate Program in Biosciences and Physiopathology, State University of Maringá, 87020-900, Maringá-PR, Brazil.
Graduate Program in Health Sciences, State University of Maringá, 87020-900, Maringá-PR, Brazil.
Int J Antimicrob Agents. 2022 May;59(5):106578. doi: 10.1016/j.ijantimicag.2022.106578. Epub 2022 Apr 1.
The objective of this systematic review was to retrieve and examine published studies related to in vitro and in vivo evaluation of disulfiram for the treatment of bacterial infections. Five scientific databases (PubMed, Embase, Scopus, Web of Science, and Latin American and Caribbean Health Sciences Literature) were searched to retrieve the maximum literature regarding the study's aim. The search strategy retrieved a total of 870 studies, of which 31 were included and 19 approached disulfiram as the primary aim and 12 included it as a secondary finding from other investigational objectives. The evidence pointed out five main aspects of pre-clinical testing regarding disulfiram antibacterial activity, namely spectrum of antimicrobial action, drug combinations, intracellular studies, animal studies and bacterial targets. Findings to emerge from this study are the observed potential of disulfiram as a non-antibiotic drug being proposed as a potential drug to contribute to the treatment of bacterial diseases usually with few treatment alternatives in the context of drug resistance. We evaluated the potency and selectivity of disulfiram, which indeed until now shows potential to be explored for use as an adjunctive chemical to antimicrobial ones. Even with the level of evidence being reserved, the potential of combining disulfiram with other drugs, already used or new to be used for the treatment of mycobacterial diseases, as well as its likely immunomodulatory effect, deserve to be further investigated. Furthermore, the copper-dependent mode of action in Gram-positive bacteria is an alternative to be explored in drug design or repurposing of chemicals.
本系统评价的目的是检索和检查有关体外和体内评估双硫仑治疗细菌感染的已发表研究。为了检索与研究目的相关的最大文献，我们在五个科学数据库（PubMed、Embase、Scopus、Web of Science 和拉丁美洲及加勒比健康科学文献）中进行了检索。该检索策略共检索到 870 项研究，其中 31 项被纳入，19 项将双硫仑作为主要目标，12 项将其作为其他研究目标的次要发现纳入。证据指出了关于双硫仑抗菌活性的临床前测试的五个主要方面，即抗菌作用谱、药物组合、细胞内研究、动物研究和细菌靶标。从这项研究中得出的发现是，观察到双硫仑作为一种非抗生素药物的潜在作用，被提议作为一种潜在药物，以有助于治疗通常耐药情况下治疗选择很少的细菌疾病。我们评估了双硫仑的效力和选择性，事实上，到目前为止，它显示出作为一种辅助化学物质与抗菌药物联合使用的潜力。即使证据水平有限，将双硫仑与其他药物联合使用的潜力，无论是已经用于还是新用于治疗分枝杆菌病的药物，以及其可能的免疫调节作用，都值得进一步研究。此外，铜依赖性作用模式在革兰氏阳性菌中是一种可供探索的药物设计或化学物质再利用的替代方法。
