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Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia

Background: Vancomycin-resistant Enterococcus faecium (VRE) in particular has evolved as an important cause of hospital acquired infection, especially in immunocompromised hosts. Methods: We present a complex case of a patient with relapsed acute myeloid leukemia who underwent allogenic hematopoieti...

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Detalles Bibliográficos
Autores principales: Wenzler, Eric, Adeel, Alina, Wu, Tiffany, Jurkovic, Michele, Walder, Jeremy, Ramasra, Emily, Campion, Maureen, Cerny, Jan, Theodoropoulos, Nicole M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482274/
https://www.ncbi.nlm.nih.gov/pubmed/34563001
http://dx.doi.org/10.3390/idr13030076
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author Wenzler, Eric
Adeel, Alina
Wu, Tiffany
Jurkovic, Michele
Walder, Jeremy
Ramasra, Emily
Campion, Maureen
Cerny, Jan
Theodoropoulos, Nicole M.
author_facet Wenzler, Eric
Adeel, Alina
Wu, Tiffany
Jurkovic, Michele
Walder, Jeremy
Ramasra, Emily
Campion, Maureen
Cerny, Jan
Theodoropoulos, Nicole M.
author_sort Wenzler, Eric
collection PubMed
description Background: Vancomycin-resistant Enterococcus faecium (VRE) in particular has evolved as an important cause of hospital acquired infection, especially in immunocompromised hosts. Methods: We present a complex case of a patient with relapsed acute myeloid leukemia who underwent allogenic hematopoietic stem cell transplantation complicated by persistent VRE bacteremia and meningitis. To optimize therapy, various blood and cerebrospinal fluid (CSF) samples were sent to a research laboratory for extensive susceptibility testing, pharmacokinetic analyses, and time-kill experiments. Results: In vitro testing revealed resistance to all first-line treatment options and CSF sampling demonstrated sub-optimal central nervous system concentrations achieved by each antimicrobial agent administered in relation to their respective MIC value. Time-kill analyses at observed CSF concentrations confirmed the lack of bactericidal activity despite use of a four-drug combination regimen. Conclusions: This work is the first to report CSF concentrations of oritavancin and tedizolid in humans and adds to the limited data regarding in vitro susceptibility of new antimicrobial agents such as eravacycline, omadacycline, and lefamulin against VRE. Our study provides new insights into various aspects of treatment of extensively drug-resistant Enterococcus faecium meningitis and bacteremia and supports the continued pursuit of precision medicine for these challenging cases.
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spelling pubmed-84822742021-10-01 Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia Wenzler, Eric Adeel, Alina Wu, Tiffany Jurkovic, Michele Walder, Jeremy Ramasra, Emily Campion, Maureen Cerny, Jan Theodoropoulos, Nicole M. Infect Dis Rep Article Background: Vancomycin-resistant Enterococcus faecium (VRE) in particular has evolved as an important cause of hospital acquired infection, especially in immunocompromised hosts. Methods: We present a complex case of a patient with relapsed acute myeloid leukemia who underwent allogenic hematopoietic stem cell transplantation complicated by persistent VRE bacteremia and meningitis. To optimize therapy, various blood and cerebrospinal fluid (CSF) samples were sent to a research laboratory for extensive susceptibility testing, pharmacokinetic analyses, and time-kill experiments. Results: In vitro testing revealed resistance to all first-line treatment options and CSF sampling demonstrated sub-optimal central nervous system concentrations achieved by each antimicrobial agent administered in relation to their respective MIC value. Time-kill analyses at observed CSF concentrations confirmed the lack of bactericidal activity despite use of a four-drug combination regimen. Conclusions: This work is the first to report CSF concentrations of oritavancin and tedizolid in humans and adds to the limited data regarding in vitro susceptibility of new antimicrobial agents such as eravacycline, omadacycline, and lefamulin against VRE. Our study provides new insights into various aspects of treatment of extensively drug-resistant Enterococcus faecium meningitis and bacteremia and supports the continued pursuit of precision medicine for these challenging cases. MDPI 2021-09-08 /pmc/articles/PMC8482274/ /pubmed/34563001 http://dx.doi.org/10.3390/idr13030076 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Wenzler, Eric
Adeel, Alina
Wu, Tiffany
Jurkovic, Michele
Walder, Jeremy
Ramasra, Emily
Campion, Maureen
Cerny, Jan
Theodoropoulos, Nicole M.
Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia
title Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia
title_full Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia
title_fullStr Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia
title_full_unstemmed Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia
title_short Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant Enterococcus faecium Meningitis and Bacteremia
title_sort inadequate cerebrospinal fluid concentrations of available salvage agents further impedes the optimal treatment of multidrug-resistant enterococcus faecium meningitis and bacteremia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482274/
https://www.ncbi.nlm.nih.gov/pubmed/34563001
http://dx.doi.org/10.3390/idr13030076
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