Amphotericin B Penetrates into the Central Nervous System through Focal Disruption of the Blood-Brain Barrier in Experimental Hematogenous Candida Meningoencephalitis

Author:

Petraitis Vidmantas12,Petraitiene Ruta12,Valdez Jessica M.23,Pyrgos Vasilios2,Lizak Martin J.4,Klaunberg Brenda A.5,Kalasauskas Darius16,Basevicius Algidas7,Bacher John D.8,Benjamin Daniel K.9,Hope William W.1011ORCID,Walsh Thomas J.12121314

Affiliation:

1. Transplantation-Oncology Infectious Diseases Program, Division of Infectious Diseases, Department of Medicine, Weill Cornell Medicine of Cornell University, New York, New York, USA

2. Pediatric Oncology Branch, National Cancer Institute, Bethesda, Maryland, USA

3. University of New Mexico, Division of Pediatric Hematology Oncology, Albuquerque, New Mexico, USA

4. In Vivo NMR Center, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, Maryland, USA

5. Mouse Imaging Facility, National Institute of Neurological Disorder and Stroke, National Institutes of Health, Bethesda, Maryland, USA

6. Department of Neurosurgery, University Medical Center, Johannes Gutenberg University, Mainz, Germany

7. Department of Radiology, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania

8. Division of Veterinary Resources, Office of Research Services, National Institutes of Health, Bethesda, Maryland, USA

9. Duke Department of Pediatrics, Duke University Medical Center, Durham, North Carolina, USA

10. Antimicrobial Pharmacodynamics and Therapeutics, Department of Molecular and Clinical Pharmacology, Institute of Translational Medicine, University of Liverpool, Liverpool Health Partners, Liverpool, United Kingdom

11. Royal Liverpool and Broadgreen University Hospital Trust, Liverpool Health Partners, Liverpool, United Kingdom

12. Department of Pediatrics, Weill Cornell Medicine of Cornell University, New York, New York, USA

13. Department of Microbiology and Immunology, Weill Cornell Medicine of Cornell University, New York, New York, USA

14. New York Presbyterian Hospital, New York, New York, USA

Abstract

Hematogenous Candida meningoencephalitis (HCME) is a life-threatening complication of neonates and immunocompromised children. Amphotericin B (AmB) shows poor permeation and low cerebrospinal fluid (CSF) concentrations but is effective in the treatment of HCME. In order to better understand the mechanism of CNS penetration of AmB, we hypothesized that AmB may achieve focally higher concentrations in infected CNS lesions.

Funder

Intramural Research Program of the National Institutes of Health

Save Our Kids Foundation

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

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