Caspofungin sequestration in a polyacrylonitrile-derived filter: Increasing the dose does not mitigate sequestration.

Abstract

OBJECTIVES:

Critically ill patients frequently require continuous renal replacement therapy. Echinocandins are recommended as first-line treatment of candidemia. Preliminary results suggested echinocandin sequestration in a polyacrylonitrile filter. The present study aimed to determine whether increasing the dose might balance sequestration.

METHODS:

An STX filter (Baxter-Gambro) was used. A liquid chromatography-mass spectrometry method was used for dosage of caspofungin. In vitro drug disposition was evaluated by NeckEpur (Neckepur, Versailles, France) technology using a crystalloid medium instead of diluted/reconstituted blood, focusing on the disposition of the unbound fraction of drugs. Two concentrations were assessed.

RESULTS:

At the low dose, the mean measured initial concentration in the central compartment (CC) was 5.1 ± 0.6 mg/L. One hundred percent of the initial amount was eliminated from the CC within the 6-h session. The mean total clearance from the CC was 9.6 ± 2.5 L/h. The mean percentages of elimination resulting from sequestration and diafiltration were 96.0 ± 5.0 and 4.0 ± 5.2%, respectively. At high dose, the mean measured initial concentration in the CC was 13.1 mg/L. One hundred percent of the initial amount was eliminated from the CC within the 6-h session. The mean total clearance from the CC was 9.5 L/h. The mean percentages of elimination resulting from sequestration and filtration were 88.5% and 11.5%, respectively.

CONCLUSION:

Increasing the dose does not mitigate caspofungin sequestration in the STX filter. The results raise caution about the simultaneous use of caspofungin and polyacrylonitrile-derived filters. Intermittent modes of renal replacement therapy might be considered. For sensitive species, fluconazole might be an alternative.

• Authors: Frédéric J Baud, Vincent Jullien, Marie Desnos-Ollivier, Lionel Lamhaut, Olivier Lortholary
• Journal: International journal of antimicrobial agents (Int J Antimicrob Agents) Vol. 62 Issue 6 Pg. 107007 (Dec 2023) ISSN: 1872-7913 [Electronic] Netherlands
• PMID: 37839719 (Publication Type: Journal Article)
• Copyright: Copyright © 2023 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Chemical References

• Caspofungin
• Antifungal Agents
• polyacrylonitrile
• Echinocandins
• Acrylic Resins
• Lipopeptides

Topics

• Humans
• Caspofungin
• Antifungal Agents (therapeutic use)
• Echinocandins (therapeutic use)
• Acrylic Resins
• Lipopeptides