Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients

Autores
Fernandez, Marisa; Marson, María Elena; Mastrantonio Garrido, Guido Enrique; Corti, Marcelo; Fleitas, Ulises Emiliano; Lloveras, Susana; Lista, Nicolás; Priarone, Maria M.; Dominguez, Cecilia; Garcia-Bournissen, Facundo
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations.
Fil: Fernandez, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina
Fil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina
Fil: Corti, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Fleitas, Ulises Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina
Fil: Lloveras, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Lista, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Priarone, Maria M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Dominguez, Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Garcia-Bournissen, Facundo. Western University; Canadá
Materia
BENZNIDAZOLE
CHAGAS DISEASE
HIV/AIDS
MENINGOENCEPHALITIS
THERAPEUTIC DRUG MONITORING
TRYPANOSOMA CRUZI
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/134958
Acceder
id CONICETDig_86c37194ff33fbf6d5a3259e47402810
oai_identifier_str oai:ri.conicet.gov.ar:11336/134958
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patientsFernandez, MarisaMarson, María ElenaMastrantonio Garrido, Guido EnriqueCorti, MarceloFleitas, Ulises EmilianoLloveras, SusanaLista, NicolásPriarone, Maria M.Dominguez, CeciliaGarcia-Bournissen, FacundoBENZNIDAZOLECHAGAS DISEASEHIV/AIDSMENINGOENCEPHALITISTHERAPEUTIC DRUG MONITORINGTRYPANOSOMA CRUZIhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations.Fil: Fernandez, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; ArgentinaFil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Corti, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Fleitas, Ulises Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; ArgentinaFil: Lloveras, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Lista, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Priarone, Maria M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Dominguez, Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; ArgentinaFil: Garcia-Bournissen, Facundo. Western University; CanadáAmerican Society for Microbiology2020-12info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/134958Fernandez, Marisa; Marson, María Elena; Mastrantonio Garrido, Guido Enrique; Corti, Marcelo; Fleitas, Ulises Emiliano; et al.; Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 65; 3; 12-2020; 1-71098-6596CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01922-20info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlmhttps://journals.asm.org/doi/10.1128/AAC.01922-20.nih.gov/33361290/info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:47:02Zoai:ri.conicet.gov.ar:11336/134958instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:47:02.675CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
title Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
spellingShingle Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
Fernandez, Marisa
BENZNIDAZOLE
CHAGAS DISEASE
HIV/AIDS
MENINGOENCEPHALITIS
THERAPEUTIC DRUG MONITORING
TRYPANOSOMA CRUZI
title_short Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
title_full Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
title_fullStr Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
title_full_unstemmed Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
title_sort Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
dc.creator.none.fl_str_mv Fernandez, Marisa
Marson, María Elena
Mastrantonio Garrido, Guido Enrique
Corti, Marcelo
Fleitas, Ulises Emiliano
Lloveras, Susana
Lista, Nicolás
Priarone, Maria M.
Dominguez, Cecilia
Garcia-Bournissen, Facundo
author Fernandez, Marisa
author_facet Fernandez, Marisa
Marson, María Elena
Mastrantonio Garrido, Guido Enrique
Corti, Marcelo
Fleitas, Ulises Emiliano
Lloveras, Susana
Lista, Nicolás
Priarone, Maria M.
Dominguez, Cecilia
Garcia-Bournissen, Facundo
author_role author
author2 Marson, María Elena
Mastrantonio Garrido, Guido Enrique
Corti, Marcelo
Fleitas, Ulises Emiliano
Lloveras, Susana
Lista, Nicolás
Priarone, Maria M.
Dominguez, Cecilia
Garcia-Bournissen, Facundo
author2_role author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv BENZNIDAZOLE
CHAGAS DISEASE
HIV/AIDS
MENINGOENCEPHALITIS
THERAPEUTIC DRUG MONITORING
TRYPANOSOMA CRUZI
topic BENZNIDAZOLE
CHAGAS DISEASE
HIV/AIDS
MENINGOENCEPHALITIS
THERAPEUTIC DRUG MONITORING
TRYPANOSOMA CRUZI
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations.
Fil: Fernandez, Marisa. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina. Dirección Nacional de Instituto de Investigación. Administración Nacional de Laboratorio e Instituto de Salud "Dr. C. G. Malbrán". Instituto Nacional de Parasitología "Dr. Mario Fatala Chaben"; Argentina
Fil: Marson, María Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina
Fil: Mastrantonio Garrido, Guido Enrique. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina
Fil: Corti, Marcelo. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Fleitas, Ulises Emiliano. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Departamento de Ciencias Biológicas. Área de Toxicología; Argentina
Fil: Lloveras, Susana. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Lista, Nicolás. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Priarone, Maria M.. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Dominguez, Cecilia. Gobierno de la Ciudad de Buenos Aires. Hospital de Infecciosas "Dr. Francisco Javier Muñiz"; Argentina
Fil: Garcia-Bournissen, Facundo. Western University; Canadá
description Chagas disease reactivation in HIV-positive people is an opportunistic infection with 79 to 100% mortality. It commonly involves the central nervous system (CNS). Early treatment with trypanocidal drugs such as benznidazole (BNZ) is crucial for this severe manifestation of Trypanosoma cruzi infection. However, limited BNZ clinical pharmacology data are available, especially its concentration in the CNS. We report a series of HIV-positive patients undergoing treatment for T. cruzi meningoencephalitis, their clinical response, and cerebrospinal fluid (CSF) and plasma BNZ concentrations. Measurements were carried out using leftover samples originally obtained for routine medical care. A high-performance liquid chromatography/tandem mass spectrometry bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples. Six patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only three of the CSF samples had detectable BNZ levels, all under 1mg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2mg/ml, which is the putative trypanocidal level. We observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or not measurable in all patients, suggesting that the usual BNZ doses may be suboptimal in HIV-positive patients with T. cruzi meningoencephalitis. While drug-drug and drug-disease interactions may be in part responsible, the factors leading to low CSF BNZ levels remain to be studied in detail. These findings highlight the potential of therapeutic drug monitoring in BNZ treatment and suggest that the use of higher doses may be useful for Chagas disease CNS reactivations.
publishDate 2020
dc.date.none.fl_str_mv 2020-12
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/134958
Fernandez, Marisa; Marson, María Elena; Mastrantonio Garrido, Guido Enrique; Corti, Marcelo; Fleitas, Ulises Emiliano; et al.; Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 65; 3; 12-2020; 1-7
1098-6596
CONICET Digital
CONICET
url http://hdl.handle.net/11336/134958
identifier_str_mv Fernandez, Marisa; Marson, María Elena; Mastrantonio Garrido, Guido Enrique; Corti, Marcelo; Fleitas, Ulises Emiliano; et al.; Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients; American Society for Microbiology; Antimicrobial Agents and Chemotherapy; 65; 3; 12-2020; 1-7
1098-6596
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01922-20
info:eu-repo/semantics/altIdentifier/url/https://pubmed.ncbi.nlmhttps://journals.asm.org/doi/10.1128/AAC.01922-20.nih.gov/33361290/
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.070432

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