利法西明的预防会导致对最后一种抗生素达普米辛的耐药性
Adrianna M Turner1, Lucy Li1, Ian R Monk1
1Department of Microbiology and Immunology, The University of Melbourne at The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia.
Nature
|October 24, 2024
概括
利法西明抗生素的使用意外导致对达普素的耐药性,达普素耐药性菌 (VREfm) 感染的最后手段治疗. 这种由细菌RNA聚合酶突变驱动的交叉耐药机制威胁到关键的抗生素疗效.
科学领域:
- 微生物学
- 分子生物学
- 传染性疾病
背景情况:
- 多种药物耐药的病原体,如抗菌素Enterococcus faecium (VREfm),对全球健康构成重大威胁.
- 达普托米辛是VREfm感染的关键最后抗生素, 但仍有不明原因的耐药性.
研究的目的:
- 调查VREfm中无法解释的达普素耐药性的机制.
- 确定非相关抗生素rifaximin是否有助于达普素耐药性.
主要方法:
- 在暴露于rifaximin后,研究细菌RNA聚合酶的氨基酸变化.
- 分析了一种新型操作子 (prdRAB) 的上调及其对细胞膜重塑的影响.
- 评估这些突变对达普素结合和耐药性的影响.
主要成果:
- 暴露于瑞法西明会诱导细菌RNA聚合酶的突变,导致prdRAB操作子的上调.
- 这种操作子会导致细胞膜重塑,减少达普素的结合,并产生交叉抗性.
- 这种耐药性的突变在VREfm菌株中普遍存在.
结论:
- 以前被认为耐药性风险较低的广泛使用rifaximin可能会损害达普素的临床有效性.
- 这种意外的交叉耐药性机制突显了当前抗生素管理假设的缺陷.
- 需要紧急重新评估利法西明的使用,特别是在肝病患者中,以保持最后的抗生素.
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