Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and Bacteremia
Background: <i>Vancomycin-resistant Enterococcus faecium</i> (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 all...
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MDPI AG
2021-09-01
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| Series: | Infectious Disease Reports |
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| Online Access: | https://www.mdpi.com/2036-7449/13/3/76 |
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| author | Eric Wenzler Alina Adeel Tiffany Wu Michele Jurkovic Jeremy Walder Emily Ramasra Maureen Campion Jan Cerny Nicole M. Theodoropoulos |
| author_facet | Eric Wenzler Alina Adeel Tiffany Wu Michele Jurkovic Jeremy Walder Emily Ramasra Maureen Campion Jan Cerny Nicole M. Theodoropoulos |
| author_sort | Eric Wenzler |
| collection | DOAJ |
| description | Background: <i>Vancomycin-resistant Enterococcus faecium</i> (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 <i>Enterococcus faecium</i> meningitis and bacteremia and supports the continued pursuit of precision medicine for these challenging cases. |
| first_indexed | 2024-03-10T07:36:25Z |
| format | Article |
| id | doaj.art-12399db0ddfc46fd9f9f636e3fe82cc4 |
| institution | Directory Open Access Journal |
| issn | 2036-7449 |
| language | English |
| last_indexed | 2024-03-10T07:36:25Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Infectious Disease Reports |
| spelling | doaj.art-12399db0ddfc46fd9f9f636e3fe82cc42023-11-22T13:23:16ZengMDPI AGInfectious Disease Reports2036-74492021-09-0113384385410.3390/idr13030076Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and BacteremiaEric Wenzler0Alina Adeel1Tiffany Wu2Michele Jurkovic3Jeremy Walder4Emily Ramasra5Maureen Campion6Jan Cerny7Nicole M. Theodoropoulos8College of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USAUMass Memorial Medical Center, Division of Infectious Diseases & Immunology, UMass Medical School, Worcester, MA 01605, USACollege of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USACollege of Pharmacy, University of Illinois at Chicago, Chicago, IL 60612, USAUMass Memorial Medical Center, Department of Internal Medicine, UMass Medical School, Worcester, MA 01605, USAUMass Memorial Medical Center, Division of Infectious Diseases & Immunology, UMass Medical School, Worcester, MA 01605, USAUMass Memorial Medical Center, Department of Pharmacy, Worcester, MA 01605, USAUMass Memorial Medical Center, Division of Hematology-Oncology, UMass Medical School, Worcester, MA 01605, USAUMass Memorial Medical Center, Division of Infectious Diseases & Immunology, UMass Medical School, Worcester, MA 01605, USABackground: <i>Vancomycin-resistant Enterococcus faecium</i> (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 <i>Enterococcus faecium</i> meningitis and bacteremia and supports the continued pursuit of precision medicine for these challenging cases.https://www.mdpi.com/2036-7449/13/3/76<i>Enterococcus faecium</i>VREmeningitiscentral nervous systemcerebrospinal fluidpharmacokinetics |
| spellingShingle | Eric Wenzler Alina Adeel Tiffany Wu Michele Jurkovic Jeremy Walder Emily Ramasra Maureen Campion Jan Cerny Nicole M. Theodoropoulos Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and Bacteremia Infectious Disease Reports <i>Enterococcus faecium</i> VRE meningitis central nervous system cerebrospinal fluid pharmacokinetics |
| title | Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and Bacteremia |
| title_full | Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and Bacteremia |
| title_fullStr | Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and Bacteremia |
| title_full_unstemmed | Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and Bacteremia |
| title_short | Inadequate Cerebrospinal Fluid Concentrations of Available Salvage Agents Further Impedes the Optimal Treatment of Multidrug-Resistant <i>Enterococcus faecium</i> Meningitis and Bacteremia |
| title_sort | inadequate cerebrospinal fluid concentrations of available salvage agents further impedes the optimal treatment of multidrug resistant i enterococcus faecium i meningitis and bacteremia |
| topic | <i>Enterococcus faecium</i> VRE meningitis central nervous system cerebrospinal fluid pharmacokinetics |
| url | https://www.mdpi.com/2036-7449/13/3/76 |
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