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      The Blood–Brain Barrier and Pharmacokinetic/Pharmacodynamic Optimization of Antibiotics for the Treatment of Central Nervous System Infections in Adults

      , , , , , ,
      Antibiotics
      MDPI AG

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          Abstract

          Bacterial central nervous system (CNS) infections are serious and carry significant morbidity and mortality. They encompass many syndromes, the most common being meningitis, which may occur spontaneously or as a consequence of neurosurgical procedures. Many classes of antimicrobials are in clinical use for therapy of CNS infections, some with established roles and indications, others with experimental reporting based on case studies or small series. This review delves into the specifics of the commonly utilized antibacterial agents, updating their therapeutic use in CNS infections from the pharmacokinetic and pharmacodynamic perspectives, with a focus on the optimization of dosing and route of administration that have been described to achieve good clinical outcomes. We also provide a concise synopsis regarding the most focused, clinically relevant information as pertains to each class and subclass of antimicrobial therapeutics. CNS infection morbidity and mortality remain high, and aggressive management is critical in ensuring favorable patient outcomes while averting toxicity and upholding patient safety.

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          Most cited references213

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          Clinical practice guidelines for antimicrobial prophylaxis in surgery.

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            Antimicrobial therapeutic drug monitoring in critically ill adult patients: a Position Paper #

            Purpose This Position Paper aims to review and discuss the available data on therapeutic drug monitoring (TDM) of antibacterials, antifungals and antivirals in critically ill adult patients in the intensive care unit (ICU). This Position Paper also provides a practical guide on how TDM can be applied in routine clinical practice to improve therapeutic outcomes in critically ill adult patients. Methods Literature review and analysis were performed by Panel Members nominated by the endorsing organisations, European Society of Intensive Care Medicine (ESICM), Pharmacokinetic/Pharmacodynamic and Critically Ill Patient Study Groups of European Society of Clinical Microbiology and Infectious Diseases (ESCMID), International Association for Therapeutic Drug Monitoring and Clinical Toxicology (IATDMCT) and International Society of Antimicrobial Chemotherapy (ISAC). Panel members made recommendations for whether TDM should be applied clinically for different antimicrobials/classes. Results TDM-guided dosing has been shown to be clinically beneficial for aminoglycosides, voriconazole and ribavirin. For most common antibiotics and antifungals in the ICU, a clear therapeutic range has been established, and for these agents, routine TDM in critically ill patients appears meritorious. For the antivirals, research is needed to identify therapeutic targets and determine whether antiviral TDM is indeed meritorious in this patient population. The Panel Members recommend routine TDM to be performed for aminoglycosides, beta-lactam antibiotics, linezolid, teicoplanin, vancomycin and voriconazole in critically ill patients. Conclusion Although TDM should be the standard of care for most antimicrobials in every ICU, important barriers need to be addressed before routine TDM can be widely employed worldwide. Electronic supplementary material The online version of this article (10.1007/s00134-020-06050-1) contains supplementary material, which is available to authorized users.
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              Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines.

              The pharmacokinetics of tetracyclines and glycylcyclines are described in three groups. Group 1, the oldest group, represented by tetracycline, oxytetracycline, chlortetracycline, demeclocycline, lymecycline, methacycline and rolitetracycline is characterized by poor absorption after food. Group 2, represented by doxycycline and minocycline, is more reliably absorbed orally, while group 3, represented by the glycylcycline tigecycline, is injectable only, with an improved antibacterial spectrum compared with the tetracyclines. Though incompletely understood, the pharmacodynamic properties of the tetracyclines and glycylcyclines are summarized.
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                Author and article information

                Contributors
                (View ORCID Profile)
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                Journal
                ABSNC4
                Antibiotics
                Antibiotics
                MDPI AG
                2079-6382
                December 2022
                December 19 2022
                : 11
                : 12
                : 1843
                Article
                10.3390/antibiotics11121843
                655e5b08-4956-4821-82de-4b5060726656
                © 2022

                https://creativecommons.org/licenses/by/4.0/

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