Cerebrospinal fluid proteomics reveals the innate immunity and blood-brain barrier dysregulation in a patient with multidrug-resistant Acinetobacter baumannii ventriculitis treated with intrathecal and intravenous polymyxin B

Cerebrospinal fluid proteomics reveals the innate immunity and blood-brain barrier dysregulation in a patient with multidrug-resistant Acinetobacter baumannii ventriculitis treated with intrathecal and intravenous polymyxin B

Acinetobacter baumannii is a major pathogen of nosocomial meningitis and ventriculitis. Due to very limited antibiotic treatment options, polymyxins are often used as a last-line therapy. To optimise polymyxin use in the intraventricular environment, cerebrospinal fluid (CSF) proteomics was employed...

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Main Authors: Mengyao Li, Dongyu Liu, Phillip J. Bergen, Silin Liang, Juan Chen, Zhi Ying Kho, Jing Lu, Huiying Sun, Weiqing Hong, Xiaofen Liu, Chengying Hong, Youlian Chen, Wei Li, Hongxia You, Shunyao Xu, Yu Wang, Huaiji Gao, Chun Hin Lam, Jian Li, Xiaoyin Chen, Xueyan Liu
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Heliyon
Subjects:
Cerebrospinal fluid
Proteomics
Acinetobacter baumannii
Ventriculitis
Polymyxin B
Intrathecal and intravenous administration
Online Access:http://www.sciencedirect.com/science/article/pii/S2405844024169241
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Summary:Acinetobacter baumannii is a major pathogen of nosocomial meningitis and ventriculitis. Due to very limited antibiotic treatment options, polymyxins are often used as a last-line therapy. To optimise polymyxin use in the intraventricular environment, cerebrospinal fluid (CSF) proteomics was employed to investigate host-pathogen-polymyxin interactions in a 69-year-old patient with multidrug-resistant A. baumannii ventriculitis treated with a combination of intrathecal (ITH; 50,000 IU q24h/q48h), intraventricular (IVT; 50,000 IU q48h), and intravenous (500,000 IU, q12h) polymyxin B. CSF was collected before the first ITH dose in the ICU (0 h) and at 24 h, Day 7 and Day 26. The proteome was quantified at each time point and proteins with Qvalue <0.05 and fold change >1.2 were considered differentially expressed. Within 24 h of ITH/IVT polymyxin B administration, the innate immune system and neuroimmunity were highly active, evidenced by up-regulation of various pathways related to pathogen invasion, endocytosis and neutrophil degranulation. Blood-brain barrier impairment had worsened at 24 h but signs of repair were evident on Day 7 and Day 26. This is the first CSF proteomic study with polymyxins. Our findings provide critical mechanistic insights into optimizing ITH/IVT polymyxin administration.
ISSN:2405-8440

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