New Class of Adjuvants Enables Lower Dosing of Colistin Against Acinetobacter baumannii,ACS Infectious Diseases

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New Class of Adjuvants Enables Lower Dosing of Colistin Against Acinetobacter baumannii
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2018-06-11 00:00:00 , DOI: 10.1021/acsinfecdis.8b00103
Bradley M. Minrovic ₁ , David Jung ₂ , Roberta J. Melander ₁ , Christian Melander ₁

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Antibiotic resistance has become increasingly prevalent over the past few decades, and this combined with a dearth in the development of new classes of antibiotics to treat multidrug resistant Gram-negative infections has led to a significant global health problem and the increased usage of colistin as the last resort antibiotic. Colistin, however, presents dose dependent toxicity in the clinic. One potential approach to combatting this problem is the use of an antibiotic adjuvant, a compound that is nontoxic to the bacteria that enhances the potency of colistin and ultimately allows for reducing dosing. Herein, we present a new urea-containing class of 2-aminoimidazole-based adjuvants that potentiates colistin activity against colistin-sensitive Acinetobacter baumannii. Lead compounds enabled 1000-fold reduction in the minimum inhibitory concentration of colistin in vitro and showed efficacy in a Galleria mellonella infection model, representing the first step toward validating the potential of employing these adjuvants to lower colistin dosage.

中文翻译：

新型佐剂可降低针对鲍曼不动杆菌的colistin剂量

在过去的几十年中，对抗生素的抗药性变得越来越普遍，加之对治疗耐多药革兰氏阴性菌感染的新型抗生素的开发匮乏，已经导致了严重的全球健康问题，并且粘菌素的使用量增加了。不得已的抗生素。然而，共利斯汀在临床上表现出剂量依赖性毒性。解决此问题的一种潜在方法是使用抗生素佐剂，该佐剂对细菌无毒，可增强大肠粘菌素的效力，并最终减少剂量。在这里，我们提出了一种新的含脲类的2-氨基咪唑类佐剂，可增强大肠菌素对大肠菌素敏感鲍曼不动杆菌的活性。。铅化合物能够使体外大肠菌素的最低抑制浓度降低1000倍，并且在马洛菌感染模型中显示出功效，代表着验证使用这些佐剂降低大肠菌素剂量的潜力的第一步。

更新日期：2018-06-11

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