Repurposing niclosamide for intestinal decolonization of vancomycin-resistant enterococci
Repurposing niclosamide for intestinal decolonization of vancomycin-resistant enterococci
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DOI：
10.1016/j.ijantimicag.2018.02.003
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发表时间：
2018-06-01
影响因子：
10.8
通讯作者：
Seleem, Mohamed N.
中科院分区：
文献类型：
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作者：
Mohammad, Haroon;AbdelKhalek, Ahmed;Seleem, Mohamed N.
肠球菌是存在于人类胃肠道中的肠道微生物。虽然通常对宿主无害，但对万古霉素（VRE）表现出耐药性的肠球菌菌株与免疫功能低下患者的高感染率和死亡率相关。VRE的非定殖化是抑制高度易感患者感染的关键策略。然而，临床上缺乏对VRE有效的去殖民化剂。目前的研究发现，氯硝柳胺，驱虫药，对临床分离的耐万古霉素屎肠球菌（最低抑菌浓度1-8 μ g/mL）有很强的抗菌活性。E.即使在多次（10）连续传代后也不能分离出对氯硝柳胺具有抗性的屎肠菌突变体。基于这些有希望的体外结果和氯硝柳胺穿过胃肠道的有限渗透性（口服给药时），在VRE定殖减少小鼠模型中评价了氯硝柳胺。值得注意的是，氯硝柳胺优于利奈唑胺，利奈唑胺是临床上用于治疗VRE感染的抗生素。氯硝柳胺在降低万古霉素耐药大肠埃希菌负荷方面与雷莫拉宁一样有效。仅在治疗8天后，感染小鼠的粪便、盲肠内容物和回肠内容物中的粪便。相比之下，利奈唑胺无法降低小鼠胃肠道中的VRE负荷。所获得的结果表明，氯硝柳胺值得进一步评价作为一种新的去殖民化剂，以抑制VRE感染。(c)2018 Elsevier B. V.和国际化疗学会。All rights reserved.
Enterococci are commensal micro-organisms present in the gastrointestinal tract of humans. Although normally innocuous to the host, strains of enterococcus exhibiting resistance to vancomycin (VRE) have been associated with high rates of infection and mortality in immunocompromised patients. Decolonization of VRE represents a key strategy to curb infection in highly-susceptible patients. However, there is a dearth of decolonizing agents available clinically that are effective against VRE. The present study found that niclosamide, an anthelmintic drug, has potent antibacterial activity against clinical isolates of vancomycin-resistant Enterococcus faecium (minimum inhibitory concentration 1-8 mu g/mL). E. faecium mutants exhibiting resistance to niclosamide could not be isolated even after multiple (10) serial passages. Based upon these promising in-vitro results and the limited permeability of niclosamide across the gastrointestinal tract (when administered orally), niclosamide was evaluated in a VRE colonization-reduction murine model. Remarkably, niclosamide outperformed linezolid, an antibiotic used clinically to treat VRE infections. Niclosamide was as effective as ramoplanin in reducing the burden of vancomycin-resistant E. faecium in the faeces, caecal content and ileal content of infected mice after only 8 days of treatment. Linezolid, in contrast, was unable to decrease the burden of VRE in the gastrointestinal tract of mice. The results obtained indicate that niclosamide warrants further evaluation as a novel decolonizing agent to suppress VRE infections. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.