A retrospective study on the impact of glucocorticoids on the efficacy of posaconazole in the prevention/treatment of invasive fungal infections in patients with hematological malignancies

Abstract

Background: Posaconazole (PCZ) has been used to prevent and treat invasive fungal infections in immunocompromised patients with hematological malignancies. There is a significant correlation between plasma drug concentration and the efficacy of posaconazole.

Objective: sThis study aimed to investigate the effects of glucocorticoid on PCZ C_min and on the outcome of PCZ prevention/treatment of invasive fungal infections.

Methods: We conducted a retrospective study at a tertiary hospital, examining patients who were administered posaconazole oral suspension between September 2021 and September 2023, to assess the effect of glucocorticoid on the plasma drug concentration and antifungal effect of posaconazole.

Results: (Ⅰ) The concomitant usage of glucocorticoid reduced PCZ C_min from 1310.00 (648.48，2550.00) ng/mL to 1085.00 (529.79，1767.50) ng/mL (p = 0.032), and the C_min/Dose (C/D) decreased from 2.14 (0.98, 4.10) ng/mL/mg to 1.66 (0.86, 2.73) ng/mL/mg (p = 0.038). (Ⅱ) There was a significant difference in PCZ C_min between patients on low-dose glucocorticoids and those on medium & high-dose glucocorticoids (1271.14 vs 720.19 ng/mL, p < 0.001). (Ⅲ) PCZ C_min was significantly lower in patients with longer glucocorticoid duration than with shorter (p = 0.013). (Ⅳ) Compared with PCZ alone, the concomitant usage of PPIs, glucocorticoids, and PPIs & glucocorticoids significantly reduced PCZ C_min (p < 0.001, p= 0.001, p= 0.001).

Conclusions: The concomitant usage of glucocorticoid can significantly reduce PCZ C_min, and this decrease has a correlation with the dose and duration of glucocorticoid. However, glucocorticoid may not affect the clinical outcome of posaconazole in the prevention/treatment of invasive fungal infections.

Keywords

Posaconazole / Retrospective study / Glucocorticoid / Invasive fungal infection / Plasma drug concentration

Declarations

Not applicable.

Authors' contributions

S. Yuan: Writing - review and editing, writing - original draft, visualization, project administration, methodology, investigation, formal analysis, data curation, and conceptualization. S. Liu: Writing - review and editing, writing - original draft, visualization, project administration, methodology, investigation, formal analysis, data curation, and conceptualization. Y. Zhao: Project administration, methodology, and investigation. Z. Wang: Project administration, methodology, and investigation. Y. Liu: Supervision, resources, project administration, and funding acquisition. J. Yu: Supervision, resources, project administration, and funding acquisition.

Ethics approval and consent to participate

This retrospective study was approved by the Hospital Ethics Committee (Approval No.: 20200638).

Consent for publication

Not applicable.

Availability of data and materials

The data that support the findings of this study are available from the corresponding author upon reasonable request.

Funding

This work was funded by [2021 Hebei Province Medical Science Research Project] (No.20210368) and [Hebei Province Government funded Clinical Medical Talents Training Project] (No. ZF2024130).

Declarations of Competing interests

The authors declare that they have no competing interests.

Acknowledgements

Thanks to all the physicians, pharmacists, patients, and colleagues who supported this study. This study was completed with the co-operation of the clinical pharmacy department, laboratory department, and hematology department. Physicians provided treatment and nur-sing services to patients. Laboratory staf carried out pathogen culture to assist in the diagnosis of invasive fungal infection. Clinical phar-macists collected and collated patient information.

Authors' other information

Not applicable.

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