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Clinical Therapeutics

Benznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive Patients

Marisa L. Fernández, María E. Marson, Guido E. Mastrantonio, Marcelo A. Corti, Ulises Fleitas, Susana C. Lloveras, Nicolas Lista, Maria M. Priarone, Cecilia Domínguez, Facundo Garcia-Bournissen
Marisa L. Fernández
aHospital de Infecciosas FJ Muñiz, Buenos Aires, Argentina
bInstituto Nacional de Parasitología Dr M Fatala Chaben, ANLIS Dr C Malbran, Ministerio de Salud, Buenos Aires, Argentina
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  • ORCID record for Marisa L. Fernández
María E. Marson
cUPL (CICpBA-UNLP), Área Toxicología, Facultad de Ciencias Exactas/UNLP/CONICET, La Plata, Argentina
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Guido E. Mastrantonio
cUPL (CICpBA-UNLP), Área Toxicología, Facultad de Ciencias Exactas/UNLP/CONICET, La Plata, Argentina
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Marcelo A. Corti
aHospital de Infecciosas FJ Muñiz, Buenos Aires, Argentina
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Ulises Fleitas
cUPL (CICpBA-UNLP), Área Toxicología, Facultad de Ciencias Exactas/UNLP/CONICET, La Plata, Argentina
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Susana C. Lloveras
aHospital de Infecciosas FJ Muñiz, Buenos Aires, Argentina
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Nicolas Lista
aHospital de Infecciosas FJ Muñiz, Buenos Aires, Argentina
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Maria M. Priarone
aHospital de Infecciosas FJ Muñiz, Buenos Aires, Argentina
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Cecilia Domínguez
aHospital de Infecciosas FJ Muñiz, Buenos Aires, Argentina
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Facundo Garcia-Bournissen
dDivision of Paediatric Clinical Pharmacology, Department of Paediatrics, Schulich School of Medicine and Dentistry, Western University, London, Ontario, Canada
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DOI: 10.1128/AAC.01922-20
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ABSTRACT

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 1 µg/ml. Fifteen plasma samples had detectable BNZ, and 13 were above 2 µg/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.

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Benznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive Patients
Marisa L. Fernández, María E. Marson, Guido E. Mastrantonio, Marcelo A. Corti, Ulises Fleitas, Susana C. Lloveras, Nicolas Lista, Maria M. Priarone, Cecilia Domínguez, Facundo Garcia-Bournissen
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01922-20; DOI: 10.1128/AAC.01922-20

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Benznidazole in Cerebrospinal Fluid: a Case Series of Chagas Disease Meningoencephalitis in HIV-Positive Patients
Marisa L. Fernández, María E. Marson, Guido E. Mastrantonio, Marcelo A. Corti, Ulises Fleitas, Susana C. Lloveras, Nicolas Lista, Maria M. Priarone, Cecilia Domínguez, Facundo Garcia-Bournissen
Antimicrobial Agents and Chemotherapy Feb 2021, 65 (3) e01922-20; DOI: 10.1128/AAC.01922-20
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KEYWORDS

Chagas disease
Trypanosoma cruzi
meningoencephalitis
HIV/AIDS
benznidazole
therapeutic drug monitoring

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