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Clinical Therapeutics

A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges

Nilesh Kumta, Jason A. Roberts, Jeffrey Lipman, Wai Tat Wong, Gavin M. Joynt, Menino Osbert Cotta
Nilesh Kumta
aUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
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Jason A. Roberts
aUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
bCentre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia
cDepartment of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Herston, Brisbane, Queensland, Australia
dPharmacy Department, Royal Brisbane and Women’s Hospital, Brisbane, Queensland, Australia
eDivision of Anaesthesiology Critical Care Emergency and Pain Medicine, Nîmes University Hospital, University of Montpellier, Nîmes, France
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Jeffrey Lipman
aUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
cDepartment of Intensive Care Medicine, Royal Brisbane and Women’s Hospital, Herston, Brisbane, Queensland, Australia
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Wai Tat Wong
fDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China
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Gavin M. Joynt
fDepartment of Anaesthesia and Intensive Care, The Chinese University of Hong Kong, Hong Kong SAR, China
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Menino Osbert Cotta
aUniversity of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia
bCentre for Translational Anti-Infective Pharmacodynamics, School of Pharmacy, The University of Queensland, Brisbane, Queensland, Australia
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DOI: 10.1128/AAC.01998-20
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ABSTRACT

Ventriculostomy-associated infections in critically ill patients remain therapeutically challenging because of drug- and disease-related factors that contribute to suboptimal antibiotic concentrations in cerebrospinal fluid. Optimal antibiotic dosing for the treatment and prevention of such infections should be based on robust and contextually specific pharmacokinetic data. The objects of this study were to describe and critically appraise studies with reported antibiotic concentrations or pharmacokinetic data in cerebrospinal fluid of critically ill patients without meningeal inflammation. We systematically reviewed the literature to identify published reports and studies describing antibiotic concentrations, pharmacokinetics, and pharmacokinetics/pharmacodynamics in cerebrospinal fluid of critically ill patients with uninflamed meninges. Fifty-eight articles met the inclusion criteria. There was significant heterogeneity in methodologies and results. When available, antibiotic pharmacokinetic parameters displayed large intersubject variability. Intraventricular dosing achieved substantially higher antibiotic concentrations in cerebrospinal fluid than did intravenous doses. Few studies conducted a robust pharmacokinetic analysis and described relevant clinical pharmacokinetic/pharmacodynamic indices and exposure targets in cerebrospinal fluid. Robust and clinically relevant antibiotic pharmacokinetic data describing antibiotic disposition in cerebrospinal fluid are necessary. Such studies should use a standardized approach to accurately describe pharmacokinetic variability. These data should ideally be tied to clinical outcomes whereby therapeutic targets in the cerebrospinal fluid can be better defined. Altered dosing strategies, in conjunction with exploring the utility of therapeutic drug monitoring, can then be developed to optimize antibiotic exposure with the goal of improving outcomes in this difficult-to-treat patient group.

FOOTNOTES

    • Received 2 October 2020.
    • Accepted 5 October 2020.
    • Accepted manuscript posted online 19 October 2020.
  • Supplemental material is available online only.

  • Copyright © 2020 American Society for Microbiology.

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A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges
Nilesh Kumta, Jason A. Roberts, Jeffrey Lipman, Wai Tat Wong, Gavin M. Joynt, Menino Osbert Cotta
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01998-20; DOI: 10.1128/AAC.01998-20

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A Systematic Review of Studies Reporting Antibiotic Pharmacokinetic Data in the Cerebrospinal Fluid of Critically Ill Patients with Uninflamed Meninges
Nilesh Kumta, Jason A. Roberts, Jeffrey Lipman, Wai Tat Wong, Gavin M. Joynt, Menino Osbert Cotta
Antimicrobial Agents and Chemotherapy Dec 2020, 65 (1) e01998-20; DOI: 10.1128/AAC.01998-20
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KEYWORDS

antibiotics
beta-lactams
cephalosporins
aminoglycosides
fluoroquinolones
oxazolidinones
polymyxins
lipopeptides
glycopeptides
fosfomycin
metronidazole
rifampicin
pharmacokinetics
pharmacodynamics
pharmacokinetic/pharmacodynamic
ventriculitis
ventriculostomy-associated infection
external ventricular drain
Critical Illness
intensive care unit

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