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An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study

BACKGROUND: Aciclovir is effective in herpesvirus infections of the CNS. Aciclovir-induced neuropsychiatric symptoms (AINS) have been reported and are associated with high CSF concentrations of aciclovir metabolite 9-carboxymethoxymethylguanine (CMMG). Risk factors except for renal failure have not...

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Autores principales: Lindström, Johan, Helldén, Anders, Lycke, Jan, Grahn, Anna, Studahl, Marie
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857197/
https://www.ncbi.nlm.nih.gov/pubmed/31504577
http://dx.doi.org/10.1093/jac/dkz357
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author Lindström, Johan
Helldén, Anders
Lycke, Jan
Grahn, Anna
Studahl, Marie
author_facet Lindström, Johan
Helldén, Anders
Lycke, Jan
Grahn, Anna
Studahl, Marie
author_sort Lindström, Johan
collection PubMed
description BACKGROUND: Aciclovir is effective in herpesvirus infections of the CNS. Aciclovir-induced neuropsychiatric symptoms (AINS) have been reported and are associated with high CSF concentrations of aciclovir metabolite 9-carboxymethoxymethylguanine (CMMG). Risk factors except for renal failure have not been explored, and disruption of the blood–brain barrier (BBB) in acute CNS infection may be of interest. OBJECTIVES: To investigate the impact of risk factors on aciclovir and CMMG concentrations, and to relate the results to AINS. METHODS: We investigated 21 consecutively included, consenting patients treated with aciclovir or valaciclovir for herpesvirus CNS infection. Regression models were constructed to study the impact of risk factors including BBB disruption, as measured with CSF:serum albumin ratio, on CSF aciclovir and CMMG concentrations. Medical records were assessed retrospectively to identify patients with AINS. RESULTS: Increased CSF:serum albumin ratio, as well as decreased renal function and high aciclovir doses, was associated with increased aciclovir and CMMG concentrations in the CSF. We identified five patients with new neuropsychiatric symptoms; four of those were considered to have AINS and had increased CSF CMMG concentrations. Only one patient without suspicion of AINS had an increased CSF CMMG concentration. CONCLUSIONS: In patients with herpesvirus CNS infections, BBB disruption is associated with increasing aciclovir and CMMG CSF concentrations. We also found an unexpectedly high number of patients with AINS. Evaluation of CSF:serum albumin ratios, renal function and CSF concentrations of aciclovir and CMMG may all contribute to the optimization of aciclovir dosing and avoidance of AINS.
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spelling pubmed-68571972019-11-20 An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study Lindström, Johan Helldén, Anders Lycke, Jan Grahn, Anna Studahl, Marie J Antimicrob Chemother Original Research BACKGROUND: Aciclovir is effective in herpesvirus infections of the CNS. Aciclovir-induced neuropsychiatric symptoms (AINS) have been reported and are associated with high CSF concentrations of aciclovir metabolite 9-carboxymethoxymethylguanine (CMMG). Risk factors except for renal failure have not been explored, and disruption of the blood–brain barrier (BBB) in acute CNS infection may be of interest. OBJECTIVES: To investigate the impact of risk factors on aciclovir and CMMG concentrations, and to relate the results to AINS. METHODS: We investigated 21 consecutively included, consenting patients treated with aciclovir or valaciclovir for herpesvirus CNS infection. Regression models were constructed to study the impact of risk factors including BBB disruption, as measured with CSF:serum albumin ratio, on CSF aciclovir and CMMG concentrations. Medical records were assessed retrospectively to identify patients with AINS. RESULTS: Increased CSF:serum albumin ratio, as well as decreased renal function and high aciclovir doses, was associated with increased aciclovir and CMMG concentrations in the CSF. We identified five patients with new neuropsychiatric symptoms; four of those were considered to have AINS and had increased CSF CMMG concentrations. Only one patient without suspicion of AINS had an increased CSF CMMG concentration. CONCLUSIONS: In patients with herpesvirus CNS infections, BBB disruption is associated with increasing aciclovir and CMMG CSF concentrations. We also found an unexpectedly high number of patients with AINS. Evaluation of CSF:serum albumin ratios, renal function and CSF concentrations of aciclovir and CMMG may all contribute to the optimization of aciclovir dosing and avoidance of AINS. Oxford University Press 2019-12 2019-08-25 /pmc/articles/PMC6857197/ /pubmed/31504577 http://dx.doi.org/10.1093/jac/dkz357 Text en © The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Research
Lindström, Johan
Helldén, Anders
Lycke, Jan
Grahn, Anna
Studahl, Marie
An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study
title An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study
title_full An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study
title_fullStr An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study
title_full_unstemmed An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study
title_short An unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus CNS infection: a prospective observational study
title_sort unexpectedly high occurrence of aciclovir-induced neuropsychiatric symptoms in patients treated for herpesvirus cns infection: a prospective observational study
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6857197/
https://www.ncbi.nlm.nih.gov/pubmed/31504577
http://dx.doi.org/10.1093/jac/dkz357
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