Voriconazole concentration is inversely correlated with corticosteroid usage in immunocompromised patients

Imataki, Osamu; Yamaguchi, Kazunori; Uemura, Makiko; Fukuoka, Noriyasu

doi:10.1111/tid.12886

Cited by 15 publications

(12 citation statements)

References 21 publications

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“…Drug-drug interactions also arise in this context. Dexamethasone was widely used in CAPA patients and induces CYP2C9, which could decrease the VTC [ 32 ]. Thus, therapeutic drug monitoring is a cornerstone for patient management, as we faced low concentrations of voriconazole in this series with a significant delay to reach the optimal therapeutic range in CAPA vs. IAPA patients.…”

Section: Discussionmentioning

confidence: 99%

Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

Reizine

Pinceaux

Léderlin

et al. 2021

JoF

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Invasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern. Influenza-associated acute respiratory distress syndrome (ARDS) and severe COVID-19 patients are both at risk of developing invasive fungal diseases. We used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological, and radiological aspects of IAPA and CAPA in a monocentric retrospective study. A total of 120 patients were included, 71 with influenza and 49 with COVID-19-associated ARDS. Among them, 27 fulfilled the newly published criteria of IPA: 17/71 IAPA (23.9%) and 10/49 CAPA (20.4%). Kaplan–Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA patients. Radiological findings showed differences between IAPA and CAPA, with a higher proportion of features suggestive of IPA during IAPA. Lastly, a wide proportion of IPA patients had low plasma voriconazole concentrations with a higher delay to reach concentrations > 2 mg/L in CAPA vs. IAPA patients (p = 0.045). Severe COVID-19 and influenza patients appeared very similar in terms of prevalence of IPA and outcome. The dramatic consequences on the patients’ prognosis emphasize the need for a better awareness in these particular populations.

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Section: Discussionmentioning

confidence: 99%

Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

Reizine

Pinceaux

Léderlin

et al. 2021

JoF

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“…An in vitro study has identified glucocorticoid receptor binding sites in the promoter region of the CYP2C19 gene and demonstrated up‐regulation of CYP2C19, supporting an inductive effect of glucocorticoids on CYP2C19 . There are limited data regarding the interaction between voriconazole and corticosteroids in clinical practice . Dolton et al found that concomitant dexamethasone use was associated with a 3.75‐fold decrease in voriconazole concentrations .…”

Section: Dips Algorithm (Drug Interaction Probability Scale); the Intmentioning

confidence: 99%

Voriconazole hepatotoxicity as a result of steroid withdrawal in a patient with allergic bronchopulmonary aspergillosis

Blanco‐Dorado

Afonso

Bandín-Vilar

et al. 2018

Brit J Clinical Pharma

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“…In the present study, although radiological ndings were generally considered to not be suggestive of IPA during ARDS, a meticulous analysis showed several interesting differences between the images, with well-circumscribed nodules, tree in bud, and bronchial wall thickening, which were observed signi cantly more frequently in IAPA than CAPA patients. (31). Thus, therapeutic drug monitoring is a cornerstone for the patient management as we were faced in this series with low concentrations of voriconazole with a signi cant delay to reach the optimal therapeutic range in CAPA versus IAPA patients.…”

Section: Resultsmentioning

confidence: 98%

“…Drug-drug interactions also arise in this context. Dexamethasone was widely used in CAPA patients and induces CYP2C9, which could decrease the VTC (31). Thus, therapeutic drug monitoring is a cornerstone for the patient management as we were faced in this series with low concentrations of voriconazole with a signi cant delay to reach the optimal therapeutic range in CAPA versus IAPA patients.…”

Section: Resultsmentioning

confidence: 99%

Influenza- and COVID-19-associated pulmonary aspergillosis: are the pictures different?

Reizine

Pinceaux

Léderlin

et al. 2021

Preprint

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BackgroundInvasive pulmonary aspergillosis (IPA) in intensive care unit patients is a major concern, in particular for those with acute respiratory distress syndrome (ARDS). As observed previously for influenza-associated ARDS, the SARS-CoV-2 pandemic has shown a high proportion of COVID-19 patients with ARDS to be at risk of developing invasive fungal diseases.MethodsWe used the new international definitions of influenza-associated pulmonary aspergillosis (IAPA) and COVID-19-associated pulmonary aspergillosis (CAPA) to compare the demographic, clinical, biological and radiological aspects of IAPA and CAPA in a monocentric retrospective study.ResultsAmong the 120 ARDS patients included, we observed equivalent prevalence of IPA in Influenza and COVID-19 populations: 17 IAPA (23.9%) and 10 CAPA (20.4%). There were no significant differences in demographic or admission characteristics between patients with and without IPA. Kaplan-Meier curves showed significantly higher 90-day mortality for IPA patients overall (p = 0.032), whereas mortality did not differ between CAPA and IAPA. The duration of mechanical ventilation was higher for IPA patients (23 days [IQR 17–40] than those without (17 days [IQR 9–25], p = 0.038). Patients with COVID-19 and influenza associated ARDS treated with corticosteroids were more likely to develop IPA. Radiological findings of IPA in both populations using the new criteria increased sensitivity but with still poor specificity. Nonetheless, they also showed interesting differences between IAPA and CAPA with a higher proportion of features suggestive of IPA in IAPA patients. Lastly, therapeutic drug monitoring also appeared challenging since a wide proportion of IPA patients had low plasma voriconazole concentrations, with a significant higher delay to reach voriconazole concentrations > 2mg/L in CAPA versus IAPA patients (p = 0.045).ConclusionsICU patients presenting with ARDS during COVID-19 are very similar to those with severe influenza pneumonia in terms of prevalence of IPA and outcome, while CAPA is mainly favored by advanced age irrespective of the background. The dramatic consequences on the patients' prognosis emphasize the need for a better awareness in these particular populations. Larger prospective studies may help in designing the most well-adapted personalized management to prevent IPA, which represents a high burden of death in severe COVID-19 and Influenza pneumonia.

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Voriconazole concentration is inversely correlated with corticosteroid usage in immunocompromised patients

Abstract: VRCZ might be metabolized by an enzyme induced by corticosteroid treatment; therefore, intraindividual variation in VRCZ metabolism should be considered prior to concurrent treatment, especially for patients with hematological malignancies treated with corticosteroids.

Cited by 15 publications

References 21 publications

Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

Influenza- and COVID-19-Associated Pulmonary Aspergillosis: Are the Pictures Different?

Voriconazole hepatotoxicity as a result of steroid withdrawal in a patient with allergic bronchopulmonary aspergillosis

Influenza- and COVID-19-associated pulmonary aspergillosis: are the pictures different?

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