The London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
The London School of Hygiene and Tropical Medicine, London WC1E 7HT, UK.
Int J Antimicrob Agents. 2020 Jul;56(1):106002. doi: 10.1016/j.ijantimicag.2020.106002. Epub 2020 Apr 30.
Burkholderia pseudomallei causes melioidosis, a potentially lethal disease that can establish both chronic and acute infections in humans. It is inherently recalcitrant to many antibiotics, there is a paucity of effective treatment options and there is no vaccine. In the present study, the efficacies of selected aminocoumarin compounds, DNA gyrase inhibitors that were discovered in the 1950s but are not in clinical use for the treatment of melioidosis were investigated. Clorobiocin and coumermycin were shown to be particularly effective in treating B. pseudomallei infection in vivo. A novel formulation with dl-tryptophan or l-tyrosine was shown to further enhance aminocoumarin potency in vivo. It was demonstrated that coumermycin has superior pharmacokinetic properties compared with novobiocin, and the coumermycin in l-tyrosine formulation can be used as an effective treatment for acute respiratory melioidosis in a murine model. Repurposing of existing approved antibiotics offers new resources in a challenging era of drug development and antimicrobial resistance.
类鼻疽伯克霍尔德菌会引起类鼻疽病，这是一种可能致命的疾病，可在人类中引发慢性和急性感染。它对许多抗生素具有固有抗性，有效的治疗选择很少，并且没有疫苗。在本研究中，研究了在 20 世纪 50 年代发现的几种氨基香豆素化合物（DNA 拓扑异构酶抑制剂）的疗效，这些化合物并未用于治疗类鼻疽病。氯罗比菌素和柔毛霉素在体内治疗类鼻疽伯克霍尔德菌感染方面表现出特别有效。含有 dl-色氨酸或 l-酪氨酸的新型制剂显示出进一步增强体内氨基香豆素效力的作用。研究表明，柔毛霉素与新生霉素相比具有更好的药代动力学特性，并且 l-酪氨酸制剂中的柔毛霉素可作为治疗急性呼吸道类鼻疽病的有效药物在小鼠模型中使用。在药物开发和抗微生物药物耐药性的充满挑战的时代，重新利用现有的批准抗生素提供了新的资源。
