Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 Dec;66(12):1071-1078.
doi: 10.1111/myc.13653. Epub 2023 Sep 12.

Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID-19

Ralph Bertram  1 , Hans-Theodor Naumann  1 , Vanessa Bartsch  2 , Wolfgang Hitzl  3   4   5 , Martina Kinzig  6 , Golo-Sung Haarmeyer  7 , Matthias Baumgärtel  7 , Arnim Geise  7 , Dorothea Muschner  7 , Jens Nentwich  8 , Stefan John  8 , Fritz Sörgel  6   9 , Joerg Steinmann  1 , Rainer Höhl  1
Affiliations

Clinical and demographic factors affecting trough levels of isavuconazole in critically ill patients with or without COVID-19

Ralph Bertram et al. Mycoses. 2023 Dec.

Abstract

Background: The broad-spectrum antifungal isavuconazole is administered to treat invasive aspergillosis and mucormycosis.

Objectives: Isavuconazole 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 methods: Isavuconazole 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.

Results: The 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).

Conclusions: Isavuconazole 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.

Keywords: aspergillosis; infection; intensive care; isavuconazole; mucormycosis; therapeutic drug monitoring.

PubMed Disclaimer

References

REFERENCES

    1. Seyedmousavi S, Mouton JW, Verweij PE, Brüggemann RJ. Therapeutic drug monitoring of voriconazole and posaconazole for invasive aspergillosis. Expert Rev Anti Infect Ther. 2013;11(9):931-941. doi:10.1586/14787210.2013.826989
    1. Lewis JS, Wiederhold NP, Hakki M, Thompson GR. New perspectives on antimicrobial agents: isavuconazole. Antimicrob Agents Chemother. 2022;66(9):e0017722. doi:10.1128/aac.00177-22
    1. Donnelley MA, Zhu ES, Thompson GR. Isavuconazole in the treatment of invasive aspergillosis and mucormycosis infections. Infect Drug Resist. 2016;9:79-86. doi:10.2147/IDR.S81416
    1. Rybak JM, Marx KR, Nishimoto AT, Rogers PD. Isavuconazole: pharmacology, pharmacodynamics, and current clinical experience with a new triazole antifungal agent. Pharmacotherapy. 2015;35(11):1037-1051. doi:10.1002/phar.1652
    1. Schmitt-Hoffmann A, Desai A, Kowalski D, Pearlman H, Yamazaki T, Townsend R. Isavuconazole absorption following oral administration in healthy subjects is comparable to intravenous dosing, and is not affected by food, or drugs that alter stomach pH. Int J Clin Pharmacol Ther. 2016;54(8):572-580. doi:10.5414/CP202434

LinkOut - more resources