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Adsorption and caspofungin dosing during continuous renal replacement therapy

The original article was published in Critical Care 2017 21:17

In a recent letter by Aguilar et al., the pharmacokinetics of caspofungin during continuous renal replacement therapy (CRRT) and the potential impact of adsorptive membrane capacity on its removal were described [1]. In this study, administered loading caspofungin dose was 50 or 70 mg based on patient weight. As the investigators demonstrated and considering that echinocandins are highly protein-bound and non-renally eliminated, caspofungin removal with CRRT was negligible [1]. Polysulphone membranes that were used by the investigators have minimal adsorptive capacity [2]. However, highly adsorptive membranes (HAMs; e.g., AN69 surface-treated and polymethylmethacrylate filters) could potentially adsorb echinocandins effectively. HAMs’ slow saturation rate would likely increase echinocandins elimination to a clinically relevant level. This, in turn, could lower maximal concentration (Cmax). By reducing Cmax/minimal inhibitory concentration (MIC) ratio for this class of antifungals, their effectiveness could be compromised [3]. This may lead to the need for dose adjustment while on CRRT [4]. In a recent study, Roger et al. showed a higher loading dose (100 mg) is necessary for critically ill patients on CRRT, which is higher than the dosing scheme used by Aguilar et al. [5]. It is essential to highlight that despite the fact that Aguilar and colleagues found minimal caspofungin elimination by CRRT, a third of their patients had subtherapeutic blood levels. Therefore, the standard dosing scheme (50 or 70 mg based on patient weight) when HAMs are used may result in significantly low caspofungin blood levels. We believe, further studies should be conducted focusing on caspofungin dosing on CRRT with HAM filters in order to evaluate the pharmacokinetics of caspofungin and determine its correct dosing strategy.

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Abbreviations

Cmax:

maximal concentration

CRRT:

continuous renal replacement therapy

HAMs:

highly adsorptive membranes

MIC:

minimal inhibitory concentration

References

  1. 1.

    Aguilar G, Ferriols R, Lozano A, Ezquer C, Carbonell JA, Jurado A, et al. Optimal doses of caspofungin during continuous venovenous hemodiafiltration in critically ill patients. Crit Care. 2017;21:17.

  2. 2.

    Honore PM, Jacobs R, Joannes-Boyau O, De Regt J, De Waele E, et al. Newly designed CRRT membranes for sepsis and SIRS--a pragmatic approach for bedside intensivists summarizing the more recent advances: a systematic structured review. ASAIO J. 2013;59:99–106.

  3. 3.

    González de Molina F, Martínez-Alberici Mde L, Ferrer R. Treatment with echinocandins during continuous renal replacement therapy. Crit Care. 2014;18(2):218. https://doi.org/10.1186/cc13803.

  4. 4.

    Tomasa TM. Echinocandins and continuous renal replacement therapies: the role of adsorption. J Nephrol Kidney Dis. 2018;2(1):118.

  5. 5.

    Roger C, Wallis SC, Muller L, Saissi G, Lipman J, Brüggemann RJ, et al.Caspofungin population pharmacokinetics in critically ill patients undergoing continuous veno-venous haemofiltration or haemodiafiltration. Clin Pharmacokinet. 2017;56(9):1057–68. https://doi.org/10.1007/s40262-016-0495-z.

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The authors declare that they have received no external funding.

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PMH and KK designed the paper. All authors participated in drafting the manuscript, and have read and approved the final version.

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Correspondence to Patrick M. Honore.

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