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Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis

(1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA be...

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Autores principales: Gatti, Milo, Fornaro, Giacomo, Pasquini, Zeno, Zanoni, Andrea, Bartoletti, Michele, Viale, Pierluigi, Pea, Federico
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134964/
https://www.ncbi.nlm.nih.gov/pubmed/37107125
http://dx.doi.org/10.3390/antibiotics12040764
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author Gatti, Milo
Fornaro, Giacomo
Pasquini, Zeno
Zanoni, Andrea
Bartoletti, Michele
Viale, Pierluigi
Pea, Federico
author_facet Gatti, Milo
Fornaro, Giacomo
Pasquini, Zeno
Zanoni, Andrea
Bartoletti, Michele
Viale, Pierluigi
Pea, Federico
author_sort Gatti, Milo
collection PubMed
description (1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 and December 2022 were included. The concentration/dose ratio (C/D) was used as a surrogate marker of voriconazole total clearance. A receiving operating characteristic (ROC) curve analysis was performed by using C-reactive protein (CRP) or procalcitonin (PCT) values as the test variable and voriconazole C/D ratio > 0.375 (equivalent to a trough concentration [C(min)] value of 3 mg/L normalized to the maintenance dose of 8 mg/kg/day) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated; (3) Results: Overall, 50 patients were included. The median average voriconazole C(min) was 2.47 (1.75–3.33) mg/L. The median (IQR) voriconazole concentration/dose ratio (C/D) was 0.29 (0.14–0.46). A CRP value > 11.46 mg/dL was associated with the achievement of voriconazole C(min) > 3 mg/L, with an AUC of 0.667 (95% CI 0.593–0.735; p < 0.001). A PCT value > 0.3 ng/mL was associated with the attainment of voriconazole C(min) > 3 mg/L (AUC 0.651; 95% CI 0.572–0.725; p = 0.0015). (4) Conclusions: Our findings suggest that in critically ill patients with CAPA, CRP and PCT values above the identified thresholds may cause the downregulation of voriconazole metabolism and favor voriconazole overexposure, leading to potentially toxic concentrations.
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spelling pubmed-101349642023-04-28 Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis Gatti, Milo Fornaro, Giacomo Pasquini, Zeno Zanoni, Andrea Bartoletti, Michele Viale, Pierluigi Pea, Federico Antibiotics (Basel) Article (1) Background: To explore the impact of the degree of inflammation on voriconazole exposure in critically ill patients affected by COVID-associated pulmonary aspergillosis (CAPA); (2) Methods: Critically ill patients receiving TDM-guided voriconazole for the management of proven or probable CAPA between January 2021 and December 2022 were included. The concentration/dose ratio (C/D) was used as a surrogate marker of voriconazole total clearance. A receiving operating characteristic (ROC) curve analysis was performed by using C-reactive protein (CRP) or procalcitonin (PCT) values as the test variable and voriconazole C/D ratio > 0.375 (equivalent to a trough concentration [C(min)] value of 3 mg/L normalized to the maintenance dose of 8 mg/kg/day) as the state variable. Area under the curve (AUC) and 95% confidence interval (CI) were calculated; (3) Results: Overall, 50 patients were included. The median average voriconazole C(min) was 2.47 (1.75–3.33) mg/L. The median (IQR) voriconazole concentration/dose ratio (C/D) was 0.29 (0.14–0.46). A CRP value > 11.46 mg/dL was associated with the achievement of voriconazole C(min) > 3 mg/L, with an AUC of 0.667 (95% CI 0.593–0.735; p < 0.001). A PCT value > 0.3 ng/mL was associated with the attainment of voriconazole C(min) > 3 mg/L (AUC 0.651; 95% CI 0.572–0.725; p = 0.0015). (4) Conclusions: Our findings suggest that in critically ill patients with CAPA, CRP and PCT values above the identified thresholds may cause the downregulation of voriconazole metabolism and favor voriconazole overexposure, leading to potentially toxic concentrations. MDPI 2023-04-16 /pmc/articles/PMC10134964/ /pubmed/37107125 http://dx.doi.org/10.3390/antibiotics12040764 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gatti, Milo
Fornaro, Giacomo
Pasquini, Zeno
Zanoni, Andrea
Bartoletti, Michele
Viale, Pierluigi
Pea, Federico
Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis
title Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis
title_full Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis
title_fullStr Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis
title_full_unstemmed Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis
title_short Impact of Inflammation on Voriconazole Exposure in Critically ill Patients Affected by Probable COVID-19-Associated Pulmonary Aspergillosis
title_sort impact of inflammation on voriconazole exposure in critically ill patients affected by probable covid-19-associated pulmonary aspergillosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10134964/
https://www.ncbi.nlm.nih.gov/pubmed/37107125
http://dx.doi.org/10.3390/antibiotics12040764
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