Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID‐19
BackgroundThe broad‐spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis.ObjectivesIsavuconazole plasma concentrations in critically ill ICU patients with or without COVID‐19 and invasive fungal infection were determined, and factors for sub‐therapeutic...
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Veröffentlicht in: | Mycoses 2023-12, Vol.66 (12), p.1071-1078 |
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creator | Bertram, Ralph Naumann, Hans‐Theodor Bartsch, Vanessa Hitzl, Wolfgang Kinzig, Martina Haarmeyer, Golo‐Sung Baumgärtel, Matthias Geise, Arnim Muschner, Dorothea Nentwich, Jens John, Stefan Sörgel, Fritz Steinmann, Joerg Höhl, Rainer |
description | BackgroundThe broad‐spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis.ObjectivesIsavuconazole plasma concentrations in critically ill ICU patients with or without COVID‐19 and invasive fungal infection were determined, and factors for sub‐therapeutic drug levels ( 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001).ConclusionsIsavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed. |
doi_str_mv | 10.1111/myc.13653 |
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Concentrations determined 20–28 h after previous dosing were defined as trough (Cmin) levels. A total of 160 Cmin levels from 62 patients with invasive fungal infections were analysed, 30 of which suffering from COVID‐19. Patient characteristics included into univariable and multivariable analyses were gender, age, COVID‐19 status, body mass index (BMI), sepsis‐related organ failure (SOFA) score, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) requirement.ResultsThe mean Cmin of isavuconazole in all patients was 1.64 μg/mL (interquartile range 0.83–2.24 μg/mL, total range 0.24–5.67 μg/mL). In total, 34.4% of the Cmin values (corresponding to 46.8% of patients) were below a threshold concentration of 1 μg/mL. Drug concentrations between patients with or without COVID‐19 did not differ (p = .43). In contrast, levels were significantly lower in patients with female sex (p = .0007), age ≤ 65 years (p = .002), BMI > 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001).ConclusionsIsavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed.</description><identifier>ISSN: 0933-7407</identifier><identifier>EISSN: 1439-0507</identifier><identifier>DOI: 10.1111/myc.13653</identifier><language>eng</language><publisher>Berlin: Wiley Subscription Services, Inc</publisher><subject>Aspergillosis ; Body mass index ; COVID-19 ; Extracorporeal membrane oxygenation ; Mucormycosis ; Patients ; Plasma levels ; Renal failure ; Risk factors ; Sepsis</subject><ispartof>Mycoses, 2023-12, Vol.66 (12), p.1071-1078</ispartof><rights>2023. This article is published under http://creativecommons.org/licenses/by-nc/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c325t-2bdf6c26a0d8d54572d5d9530a48377db1bb30c355f083d747d03465bd8cf6fd3</citedby><cites>FETCH-LOGICAL-c325t-2bdf6c26a0d8d54572d5d9530a48377db1bb30c355f083d747d03465bd8cf6fd3</cites><orcidid>0000-0001-6681-9703 ; 0000-0001-6381-8991 ; 0000-0003-0654-6381 ; 0000-0001-6029-2103 ; 0000-0002-1902-7356 ; 0000-0002-7696-1479 ; 0000-0003-2983-0887 ; 0000-0002-3181-3667</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids></links><search><creatorcontrib>Bertram, Ralph</creatorcontrib><creatorcontrib>Naumann, Hans‐Theodor</creatorcontrib><creatorcontrib>Bartsch, Vanessa</creatorcontrib><creatorcontrib>Hitzl, Wolfgang</creatorcontrib><creatorcontrib>Kinzig, Martina</creatorcontrib><creatorcontrib>Haarmeyer, Golo‐Sung</creatorcontrib><creatorcontrib>Baumgärtel, Matthias</creatorcontrib><creatorcontrib>Geise, Arnim</creatorcontrib><creatorcontrib>Muschner, Dorothea</creatorcontrib><creatorcontrib>Nentwich, Jens</creatorcontrib><creatorcontrib>John, Stefan</creatorcontrib><creatorcontrib>Sörgel, Fritz</creatorcontrib><creatorcontrib>Steinmann, Joerg</creatorcontrib><creatorcontrib>Höhl, Rainer</creatorcontrib><title>Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID‐19</title><title>Mycoses</title><description>BackgroundThe broad‐spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis.ObjectivesIsavuconazole plasma concentrations in critically ill ICU patients with or without COVID‐19 and invasive fungal infection were determined, and factors for sub‐therapeutic drug levels (<1 μg/mL) were evaluated.Patients and MethodsIsavuconazole plasma levels were measured as part of therapeutic drug monitoring (TDM) in ICUs of a tertiary hospital. Concentrations determined 20–28 h after previous dosing were defined as trough (Cmin) levels. A total of 160 Cmin levels from 62 patients with invasive fungal infections were analysed, 30 of which suffering from COVID‐19. Patient characteristics included into univariable and multivariable analyses were gender, age, COVID‐19 status, body mass index (BMI), sepsis‐related organ failure (SOFA) score, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) requirement.ResultsThe mean Cmin of isavuconazole in all patients was 1.64 μg/mL (interquartile range 0.83–2.24 μg/mL, total range 0.24–5.67 μg/mL). In total, 34.4% of the Cmin values (corresponding to 46.8% of patients) were below a threshold concentration of 1 μg/mL. Drug concentrations between patients with or without COVID‐19 did not differ (p = .43). In contrast, levels were significantly lower in patients with female sex (p = .0007), age ≤ 65 years (p = .002), BMI > 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001).ConclusionsIsavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed.</description><subject>Aspergillosis</subject><subject>Body mass index</subject><subject>COVID-19</subject><subject>Extracorporeal membrane oxygenation</subject><subject>Mucormycosis</subject><subject>Patients</subject><subject>Plasma levels</subject><subject>Renal failure</subject><subject>Risk factors</subject><subject>Sepsis</subject><issn>0933-7407</issn><issn>1439-0507</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><recordid>eNpdkbtOwzAARS0EEqUw8AeWWGBIsePYTkZUXpUqsQBr5PjRunLjYjtFZYFP4Bv5EtKWibvc5ejqSgeAc4xGuM_1ciNHmDBKDsAAF6TKEEX8EAxQRUjGC8SPwUmMC4Qwr3I2AJ9jZ1srhYOiVVDppZ8FsZpbCY2QyYcIhTFaJtvOYAq-m82h02vtIvQG2ijWnfSt-PBOQ9tCGWzajrkNtM7BlUhWtynCd5vm0Idd-y7B8dPr5Pbn6xtXp-DICBf12V8Pwcv93fP4MZs-PUzGN9NMkpymLG-UYTJnAqlS0YLyXFFVUYJEURLOVYObhiBJKDWoJIoXXCFSMNqoUhpmFBmCy_3uKvi3TsdUL22U2jnRat_FOi9ZwTDnJe3Ri3_owneh7d_1VFlUDPF8S13tKRl8jEGbehXsUoRNjVG9VVH3KuqdCvILhi5-EA</recordid><startdate>20231201</startdate><enddate>20231201</enddate><creator>Bertram, Ralph</creator><creator>Naumann, Hans‐Theodor</creator><creator>Bartsch, Vanessa</creator><creator>Hitzl, Wolfgang</creator><creator>Kinzig, Martina</creator><creator>Haarmeyer, Golo‐Sung</creator><creator>Baumgärtel, Matthias</creator><creator>Geise, Arnim</creator><creator>Muschner, Dorothea</creator><creator>Nentwich, Jens</creator><creator>John, Stefan</creator><creator>Sörgel, Fritz</creator><creator>Steinmann, Joerg</creator><creator>Höhl, Rainer</creator><general>Wiley Subscription Services, Inc</general><scope>AAYXX</scope><scope>CITATION</scope><scope>M7N</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-6681-9703</orcidid><orcidid>https://orcid.org/0000-0001-6381-8991</orcidid><orcidid>https://orcid.org/0000-0003-0654-6381</orcidid><orcidid>https://orcid.org/0000-0001-6029-2103</orcidid><orcidid>https://orcid.org/0000-0002-1902-7356</orcidid><orcidid>https://orcid.org/0000-0002-7696-1479</orcidid><orcidid>https://orcid.org/0000-0003-2983-0887</orcidid><orcidid>https://orcid.org/0000-0002-3181-3667</orcidid></search><sort><creationdate>20231201</creationdate><title>Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID‐19</title><author>Bertram, Ralph ; Naumann, Hans‐Theodor ; Bartsch, Vanessa ; Hitzl, Wolfgang ; Kinzig, Martina ; Haarmeyer, Golo‐Sung ; Baumgärtel, Matthias ; Geise, Arnim ; Muschner, Dorothea ; Nentwich, Jens ; John, Stefan ; Sörgel, Fritz ; Steinmann, Joerg ; Höhl, Rainer</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c325t-2bdf6c26a0d8d54572d5d9530a48377db1bb30c355f083d747d03465bd8cf6fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aspergillosis</topic><topic>Body mass index</topic><topic>COVID-19</topic><topic>Extracorporeal membrane oxygenation</topic><topic>Mucormycosis</topic><topic>Patients</topic><topic>Plasma levels</topic><topic>Renal failure</topic><topic>Risk factors</topic><topic>Sepsis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bertram, Ralph</creatorcontrib><creatorcontrib>Naumann, Hans‐Theodor</creatorcontrib><creatorcontrib>Bartsch, Vanessa</creatorcontrib><creatorcontrib>Hitzl, Wolfgang</creatorcontrib><creatorcontrib>Kinzig, Martina</creatorcontrib><creatorcontrib>Haarmeyer, Golo‐Sung</creatorcontrib><creatorcontrib>Baumgärtel, Matthias</creatorcontrib><creatorcontrib>Geise, Arnim</creatorcontrib><creatorcontrib>Muschner, Dorothea</creatorcontrib><creatorcontrib>Nentwich, Jens</creatorcontrib><creatorcontrib>John, Stefan</creatorcontrib><creatorcontrib>Sörgel, Fritz</creatorcontrib><creatorcontrib>Steinmann, Joerg</creatorcontrib><creatorcontrib>Höhl, Rainer</creatorcontrib><collection>CrossRef</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>MEDLINE - Academic</collection><jtitle>Mycoses</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bertram, Ralph</au><au>Naumann, Hans‐Theodor</au><au>Bartsch, Vanessa</au><au>Hitzl, Wolfgang</au><au>Kinzig, Martina</au><au>Haarmeyer, Golo‐Sung</au><au>Baumgärtel, Matthias</au><au>Geise, Arnim</au><au>Muschner, Dorothea</au><au>Nentwich, Jens</au><au>John, Stefan</au><au>Sörgel, Fritz</au><au>Steinmann, Joerg</au><au>Höhl, Rainer</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID‐19</atitle><jtitle>Mycoses</jtitle><date>2023-12-01</date><risdate>2023</risdate><volume>66</volume><issue>12</issue><spage>1071</spage><epage>1078</epage><pages>1071-1078</pages><issn>0933-7407</issn><eissn>1439-0507</eissn><abstract>BackgroundThe broad‐spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis.ObjectivesIsavuconazole plasma concentrations in critically ill ICU patients with or without COVID‐19 and invasive fungal infection were determined, and factors for sub‐therapeutic drug levels (<1 μg/mL) were evaluated.Patients and MethodsIsavuconazole plasma levels were measured as part of therapeutic drug monitoring (TDM) in ICUs of a tertiary hospital. Concentrations determined 20–28 h after previous dosing were defined as trough (Cmin) levels. A total of 160 Cmin levels from 62 patients with invasive fungal infections were analysed, 30 of which suffering from COVID‐19. Patient characteristics included into univariable and multivariable analyses were gender, age, COVID‐19 status, body mass index (BMI), sepsis‐related organ failure (SOFA) score, renal replacement therapy (RRT) and extracorporeal membrane oxygenation (ECMO) requirement.ResultsThe mean Cmin of isavuconazole in all patients was 1.64 μg/mL (interquartile range 0.83–2.24 μg/mL, total range 0.24–5.67 μg/mL). In total, 34.4% of the Cmin values (corresponding to 46.8% of patients) were below a threshold concentration of 1 μg/mL. Drug concentrations between patients with or without COVID‐19 did not differ (p = .43). In contrast, levels were significantly lower in patients with female sex (p = .0007), age ≤ 65 years (p = .002), BMI > 25 (p = .006), SOFA score > 12 (p = .026), RRT (p = .017) and ECMO requirement (p = .001).ConclusionsIsavuconazole plasma levels can be negatively affected by patients' risk factors, supportive renal replacement and ECMO therapy. Future prospective studies analysing the relevance of isavuconazole drug levels in ICU patient outcome are urgently needed.</abstract><cop>Berlin</cop><pub>Wiley Subscription Services, Inc</pub><doi>10.1111/myc.13653</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-6681-9703</orcidid><orcidid>https://orcid.org/0000-0001-6381-8991</orcidid><orcidid>https://orcid.org/0000-0003-0654-6381</orcidid><orcidid>https://orcid.org/0000-0001-6029-2103</orcidid><orcidid>https://orcid.org/0000-0002-1902-7356</orcidid><orcidid>https://orcid.org/0000-0002-7696-1479</orcidid><orcidid>https://orcid.org/0000-0003-2983-0887</orcidid><orcidid>https://orcid.org/0000-0002-3181-3667</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aspergillosis Body mass index COVID-19 Extracorporeal membrane oxygenation Mucormycosis Patients Plasma levels Renal failure Risk factors Sepsis |
title | Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID‐19 |
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