{
    "abstract": "Central nervous system (CNS) infections caused by carbapenem-resistant Gram-negative bacteria (CR-GNB) present a major health and economic burden worldwide. This multicentre prospective study aimed to assess the feasibility and usefulness of CSF therapeutic drug monitoring (TDM) after intrathecal/intraventricular administration of polymyxin B in patients with CNS infections.\nForty-two patients treated with intrathecal/intraventricular administration of polymyxin B against CR-GNB-induced CNS infections were enrolled. CSF trough level (Cmin) was collected beginning on Day 2 post-polymyxin B initiation and thereafter. The primary outcomes were clinical cure and 28-day all-cause mortality.\nAll patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P\u200a=\u200a0.011]. In addition, with MICs\u200a\u2264\u200a0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P\u200a=\u200a0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin.\nAfter intrathecal/intraventricular administration of polymyxin B, CSF concentrations fluctuated considerably inter- and intra-individual. Polymyxin B CSF Cmin above 2.0 mg/L was associated with clinical cure when MICs were\u200a\u2264\u200a0.5 mg/L, and the feasibility of TDM warrants additional clinical studies.",
    "authors": [
        {
            "affiliation": "Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China.\nHenan Province Engineering Research Center for Application and Translation of Precision Clinical Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
            "firstname": "Peile",
            "initials": "P",
            "lastname": "Wang"
        },
        {
            "affiliation": "Department of General Intensive Care Unit, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nHenan Province Engineering Research Center for Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
            "firstname": "Shaohua",
            "initials": "S",
            "lastname": "Liu"
        },
        {
            "affiliation": "Department of Neuro-Intensive Care Unit, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
            "firstname": "Xia",
            "initials": "X",
            "lastname": "He"
        },
        {
            "affiliation": "Department of Neuro-Intensive Care Unit, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
            "firstname": "Wang",
            "initials": "W",
            "lastname": "Miao"
        },
        {
            "affiliation": "Department of General Intensive Care Unit, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nHenan Province Engineering Research Center for Critical Care Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
            "firstname": "Tongwen",
            "initials": "T",
            "lastname": "Sun"
        },
        {
            "affiliation": "Department of Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.\nHenan Key Laboratory of Precision Clinical Pharmacy, Zhengzhou University, Zhengzhou, China.\nHenan Province Engineering Research Center for Application and Translation of Precision Clinical Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.",
            "firstname": "Jing",
            "initials": "J",
            "lastname": "Yang"
        }
    ],
    "conclusions": null,
    "copyrights": "\u00a9 The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site\u2014for further information please contact journals.permissions@oup.com.",
    "doi": "10.1093/jac/dkae193",
    "journal": "The Journal of antimicrobial chemotherapy",
    "keywords": [],
    "methods": null,
    "publication_date": "2024-06-13",
    "pubmed_id": "38870067",
    "results": "All patients started with intrathecal/intraventricular administration of polymyxin B at a dose of 5 g/day, corresponding to a median CSF Cmin of 2.93 mg/L (range, 0.21-25.74 mg/L). Clinical cure was 71.4%, and the median CSF Cmin of this group was higher than that of clinical failure group [3.31 (IQR, 1.73-5.62) mg/L versus 2.25 (IQR, 1.09-4.12) mg/L; P\u200a=\u200a0.011]. In addition, with MICs\u200a\u2264\u200a0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P\u200a=\u200a0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin.",
    "title": "Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection.",
    "xml": "<Element 'PubmedArticle' at 0x788503693240>"
}