Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA.
Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana, USA
Antimicrob Agents Chemother. 2020 May 21;64(6). doi: 10.1128/AAC.02115-19.
, the leading cause of nosocomial infections, is an urgent health threat worldwide. The increased incidence and severity of disease, the high recurrence rates, and the dearth of effective anticlostridial drugs have created an urgent need for new therapeutic agents. In an effort to discover new drugs for the treatment of infections (CDIs), we investigated a panel of FDA-approved antiparasitic drugs against and identified diiodohydroxyquinoline (DIHQ), an FDA-approved oral antiamoebic drug. DIHQ exhibited potent activity against 39 isolates, inhibiting growth of 50% and 90% of these isolates at concentrations of 0.5 μg/ml and 2 μg/ml, respectively. In a time-kill assay, DIHQ was superior to vancomycin and metronidazole, reducing a high bacterial inoculum by 3 log within 6 h. Furthermore, DIHQ reacted synergistically with vancomycin and metronidazole against Moreover, at subinhibitory concentrations, DIHQ was superior to vancomycin and metronidazole in inhibiting two key virulence factors of , toxin production and spore formation. Additionally, DIHQ did not inhibit the growth of key species that compose the host intestinal microbiota, such as , , and spp. Collectively, our results indicate that DIHQ is a promising anticlostridial drug that warrants further investigation as a new therapeutic for CDIs.
艰难梭菌是医院获得性感染的主要原因，是全球范围内的一个紧迫的健康威胁。疾病的发病率和严重程度增加，复发率高，有效的抗梭菌药物匮乏，这一切都迫切需要新的治疗药物。为了寻找治疗艰难梭菌感染（CDI）的新药，我们研究了一组美国食品和药物管理局（FDA）批准的抗寄生虫药物，以对抗艰难梭菌，并发现了二羟碘喹啉（DIHQ），一种 FDA 批准的口服抗阿米巴病药物。DIHQ 对 39 株分离株表现出强大的活性，分别在浓度为 0.5μg/ml 和 2μg/ml 时抑制 50%和 90%的这些分离株生长。在时间杀伤试验中，DIHQ 优于万古霉素和甲硝唑，可在 6 小时内将高细菌接种物减少 3 个对数级。此外，DIHQ 与万古霉素和甲硝唑对 表现出协同作用。此外，在亚抑菌浓度下，DIHQ 在抑制艰难梭菌的两种关键毒力因子——毒素产生和孢子形成方面优于万古霉素和甲硝唑。此外，DIHQ 不会抑制宿主肠道微生物群的关键物种的生长，如 、 、和 属。总的来说，我们的结果表明，DIHQ 是一种很有前途的抗梭菌药物，值得进一步研究，作为治疗 CDI 的新疗法。
