1. Therapeutic drug monitoring of polymyxin B cerebrospinal fluid concentrations in patients with carbapenem-resistant Gram-negative bacteria-induced central nervous system infection.
- Author
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Wang P, Liu S, He X, Miao W, Sun T, and Yang J
- Subjects
- Humans, Male, Female, Middle Aged, Prospective Studies, Aged, Adult, Central Nervous System Infections drug therapy, Central Nervous System Infections cerebrospinal fluid, Central Nervous System Infections microbiology, Central Nervous System Infections mortality, Injections, Spinal, Treatment Outcome, Microbial Sensitivity Tests, Cerebrospinal Fluid microbiology, Drug Monitoring, Polymyxin B therapeutic use, Polymyxin B administration & dosage, Polymyxin B pharmacokinetics, Anti-Bacterial Agents cerebrospinal fluid, Anti-Bacterial Agents therapeutic use, Anti-Bacterial Agents pharmacokinetics, Anti-Bacterial Agents administration & dosage, Gram-Negative Bacterial Infections drug therapy, Gram-Negative Bacterial Infections cerebrospinal fluid, Gram-Negative Bacterial Infections mortality, Gram-Negative Bacterial Infections microbiology, Carbapenems therapeutic use, Carbapenems pharmacokinetics, Carbapenems pharmacology, Gram-Negative Bacteria drug effects
- Abstract
Objectives: 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., Methods: Forty-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., 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 = 0.011]. In addition, with MICs ≤ 0.5 mg/L, maintaining polymyxin B CSF Cmin above 2.0 mg/L showed a higher clinical cure rate (P = 0.041). The 28-day all-cause mortality rate was 31.0% and had no association with CSF Cmin., Conclusions: After 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 ≤ 0.5 mg/L, and the feasibility of TDM warrants additional clinical studies., (© 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—for further information please contact journals.permissions@oup.com.)
- Published
- 2024
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