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
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
Affiliations
Mengyao Li
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China; Integrated Chinese and Western Medicine Postdoctoral Research Station, Jinan University, Guangzhou, 510632, China
Dongyu Liu
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Phillip J. Bergen
Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Melbourne, VIC, 3800, Australia
Silin Liang
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Juan Chen
Department of Pharmacy, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Zhi Ying Kho
Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Melbourne, VIC, 3800, Australia
Jing Lu
Institute of Infectious Diseases, The Second Hospital of Tianjin Medical University, 23 Pingjiang Road, Tianjin, 300211, China
Huiying Sun
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Weiqing Hong
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Xiaofen Liu
Institute of Antibiotics, Huashan Hospital, Fudan University / Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of the People's Republic of China, Shanghai 200040, China; National Clinical Research Centre for Aging and Medicine, Huashan Hospital affiliated to Fudan University, Shanghai, 200040, China
Chengying Hong
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Youlian Chen
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Wei Li
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Hongxia You
Department of Stomatology, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Shunyao Xu
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China
Yu Wang
Institute of Antibiotics, Huashan Hospital, Fudan University / Key Laboratory of Clinical Pharmacology of Antibiotics, National Health Commission of the People's Republic of China, Shanghai 200040, China; National Clinical Research Centre for Aging and Medicine, Huashan Hospital affiliated to Fudan University, Shanghai, 200040, China
Huaiji Gao
Mathematics and Statistics, School of Computing Engineering and Mathematical Sciences, La Trobe University, Melbourne, VIC, 3085, Australia
Chun Hin Lam
Faculty of Medicine, Macau University of Science and Technology, Taipa, Macau, 999078, China
Jian Li
Biomedicine Discovery Institute, Infection Program and Department of Microbiology, Monash University, Melbourne, VIC, 3800, Australia
Xiaoyin Chen
College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China; Corresponding author. College of Traditional Chinese Medicine, Jinan University, Guangzhou, 510632, China.
Xueyan Liu
Department of Critical Care Medicine, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen, 518020, China; Corresponding author. Department of ICU, The Second Clinical Medical College, Jinan University (Shenzhen People's Hospital), Shenzhen 518020, China.
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 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.
