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Article
Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients
Antimicrobial Agents and Chemotherapy
  • Marisa L. Fernández, Hospital de Infecciosas Francisco Javier Muniz
  • María E. Marson, Comision de Investigaciones Cientificas - La Plata
  • Guido E. Mastrantonio, Comision de Investigaciones Cientificas - La Plata
  • Marcelo A. Corti, Hospital de Infecciosas Francisco Javier Muniz
  • Ulises Fleitas, Comision de Investigaciones Cientificas - La Plata
  • Susana C. Lloveras, Hospital de Infecciosas Francisco Javier Muniz
  • Nicolas Lista, Hospital de Infecciosas Francisco Javier Muniz
  • Maria M. Priarone, Hospital de Infecciosas Francisco Javier Muniz
  • Cecilia Domínguez, Hospital de Infecciosas Francisco Javier Muniz
  • Facundo Garcia-Bournissen, Schulich School of Medicine & Dentistry
Document Type
Article
Publication Date
3-1-2021
URL with Digital Object Identifier
10.1128/AAC.01922-20
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 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.

Citation Information
Marisa L. Fernández, María E. Marson, Guido E. Mastrantonio, Marcelo A. Corti, et al.. "Benznidazole in cerebrospinal fluid: A case series of chagas disease meningoencephalitis in hiv-positive patients" Antimicrobial Agents and Chemotherapy Vol. 65 Iss. 3 (2021)
Available at: http://works.bepress.com/facundo-garcia-bournissen/17/