New Antibiotics for the Treatment of Nosocomial Central Nervous System Infections
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Published:2024-01-07
Issue:1
Volume:13
Page:58
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ISSN:2079-6382
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Container-title:Antibiotics
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language:en
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Short-container-title:Antibiotics
Author:
Nau Roland12, Seele Jana12, Eiffert Helmut13
Affiliation:
1. Department of Neuropathology, University Medicine Göttingen, Georg-August-University Göttingen, 37075 Göttingen, Germany 2. Department of Geriatrics, Protestant Hospital Göttingen-Weende, 37075 Göttingen, Germany 3. Amedes MVZ for Laboratory Medicine, Medical Microbiology and Infectiology, 37077 Göttingen, Germany
Abstract
Nosocomial central nervous system (CNS) infections with carbapenem- and colistin-resistant Gram-negative and vancomycin-resistant Gram-positive bacteria are an increasing therapeutic challenge. Here, we review pharmacokinetic and pharmacodynamic data and clinical experiences with new antibiotics administered intravenously for the treatment of CNS infections by multi-resistant bacteria. Cefiderocol, a new siderophore extended-spectrum cephalosporin, pharmacokinetically behaves similar to established cephalosporins and at high doses will probably be a valuable addition in our therapeutic armamentarium for CNS infections. The new glycopeptides dalbavancin, telavancin, and oritavancin are highly bound to plasma proteins. Although effective in animal models of meningitis, it is unlikely that they reach effective cerebrospinal fluid (CSF) concentrations after intravenous administration alone. The β-lactam/β-lactamase inhibitor combinations have the principal problem that both compounds must achieve adequate CSF concentrations. In the commercially available combinations, the dose of the β-lactamase inhibitor tends to be too low to achieve adequate CSF concentrations. The oxazolidinone tedizolid has a broader spectrum but a less suitable pharmacokinetic profile than linezolid. The halogenated tetracycline eravacycline does not reach CSF concentrations sufficient to treat colistin-resistant Gram-negative bacteria with usual intravenous dosing. Generally, treatment of CNS infections should be intravenous, whenever possible, to avoid adverse effects of intraventricular therapy (IVT). An additional IVT can overcome the limited penetration of many new antibiotics into CSF. It should be considered for patients in which the CNS infection responds poorly to systemic antimicrobial therapy alone.
Subject
Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology
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