BENZNIDAZOLE IN CEREBROSPINAL FLUID. A CASE SERIES OF CHAGAS DISEASE MENINGOENCEPHALITIS IN HIV POSITIVE PATIENTS.

Abstract:

:BackgroundChagas disease reactivation in HIV positive people is an opportunistic infection with 79-100% 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 is available, especially its concentration in CNS.MethodsWe 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. An HPLC-MS/MS bioanalytical method designed for BNZ plasma measurements was adapted and validated for CSF samples.ResultsSix patients were enrolled in this study from 2015 to 2019. A total of 6 CSF and 19 plasma samples were obtained. Only 3 of the CSF samples had detectable BNZ levels, all under 1 μg/mL. Although this, 15 plasma samples had detectable BNZ, and 13 were above 2 μg/mL, which is the putative trypanocidal level.ConclusionsWe observed BNZ concentrations in human CSF and plasma. CSF BNZ concentrations were low or non-measurable in all patients, suggesting that 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. The findings highlight the potential of therapeutic drug monitoring in BNZ treatment, and suggest that use of higher doses may be useful for Chagas disease CNS reactivations.

authors

Fernández ML,Marson ME,Mastrantonio GE,Corti MA,Fleitas U,Lloveras SC,Lista N,Priarone MM,Domínguez C,Garcia-Bournissen F

doi

10.1128/AAC.01922-20

subject

Has Abstract

pub_date

2020-12-23 00:00:00

eissn

0066-4804

issn

1098-6596

pii

AAC.01922-20

pub_type

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