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新型糖肽类抗生素弗拉万星在动物模型中过敏反应的实验评估

Experimental Evaluation of the Hypersensitivity Reactions of a New Glycopeptide Antibiotic Flavancin in Animal Models.

作者信息

Treshchalin Michael I, Polozkova Vasilisa A, Moiseenko Elena I, Shchekotikhin Andrey E, Dovzhenko Svetlana A, Kobrin Mikhail B, Pereverzeva Eleonora R

机构信息

Gause Institute of New Antibiotics, 11 B. Pirogovskaya Street, 119021 Moscow, Russia.

Organic Chemistry Department, Mendeleyev University of Chemical Technology of Russia, 9 Miusskaya Square, 125047 Moscow, Russia.

出版信息

Pharmaceuticals (Basel). 2023 Nov 7;16(11):1569. doi: 10.3390/ph16111569.

Abstract

Glycopeptide antibiotics are still in demand in clinical practice for treating infections caused by resistant gram-positive pathogens; however, their use is limited due to severe adverse reactions. Their predominant types of side effects are immunoglobulin E-mediated or nonmediated hypersensitivity reactions. Therefore, the development of new glycopeptide antibiotics with improved toxicity profiles remains an important objective in advancing modern antimicrobial agents. We investigated a new eremomycin aminoalkylamide flavancin, its anaphylactogenic properties, influence on histamine levels in blood plasma, pseudoallergic inflammatory reaction on concanavalin A and the change in the amount of flavancin in the blood plasma after administration. It has been shown that flavancin does not demonstrate anaphylactogenic properties. The injection of flavancin resulted in a level of histamine in the blood three times lower than that caused by vancomycin. The therapeutic dose of vancomycin led to a statistically significant increase in the concanavalin A response index compared to flavancin (54% versus 3.7%). Thus, flavancin does not cause a pseudo-allergic reaction. The rapid decrease in flavancin concentration in the blood and the low levels of histamine in the plasma lead us to assume that any pseudoallergic reactions resulting from flavancin application, if they do occur in clinical practice, will be significantly less compared to the use of vancomycin.

摘要

糖肽类抗生素在临床实践中对于治疗由耐药革兰氏阳性病原体引起的感染仍然有需求;然而,由于严重的不良反应,它们的使用受到限制。它们主要的副作用类型是免疫球蛋白E介导的或非介导的超敏反应。因此,开发具有改善毒性特征的新型糖肽类抗生素仍然是推进现代抗菌药物的一个重要目标。我们研究了一种新的埃瑞霉素氨基烷基酰胺黄霉素,它的致过敏特性、对血浆中组胺水平的影响、对伴刀豆球蛋白A的类过敏炎症反应以及给药后血浆中黄霉素量的变化。结果表明,黄霉素不具有致过敏特性。注射黄霉素导致血液中的组胺水平比万古霉素引起的低三倍。与黄霉素相比,万古霉素的治疗剂量导致伴刀豆球蛋白A反应指数有统计学上的显著增加(分别为54%和3.7%)。因此,黄霉素不会引起类过敏反应。血液中黄霉素浓度的迅速下降以及血浆中组胺的低水平使我们推测,如果在临床实践中确实发生由黄霉素应用引起的任何类过敏反应,与使用万古霉素相比将显著减少。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ef5b/10675777/a89d574d348a/pharmaceuticals-16-01569-g001.jpg

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