Micafungin Plasma Levels Are Not Affected by Continuous Renal Replacement Therapy: Experience in Critically Ill Patients

Abstract

Critically ill patients often experience acute kidney injury and the need for renal replacement therapy in the course of their treatment in an intensive care unit (ICU). These patients are at an increased risk for candidiasis. Although there have been several reports of micafungin disposition during renal replacement therapy, to this date there are no data describing the elimination of micafungin during high-dose continuous venovenous hemodiafiltration with modified AN69 membranes. The aim of this prospective open-label pharmacokinetic study was to assess whether micafungin plasma levels are affected by continuous hemodiafiltration in critical ill patients using the commonly employed AN69 membrane. A total of 10 critically ill patients with micafungin treatment due to suspected or proven candidemia were included in this trial. Prefilter/postfilter micafungin clearance was measured to be 46.0 ml/min (Ϯ21.7 ml/min; n ϭ 75 individual time points), while hemofilter clearance calculated by the sieving coefficient was 0.0038 ml/min (Ϯ0.002 ml/min; n ϭ 75 individual time points). Total body clearance was measured to be 14.0 ml/min (Ϯ7.0 ml/min; n ϭ 12). The population area under the curve from 0 to 24 h (AUC 0 -24 ) was calculated as 158.5 mg · h/liter (Ϯ79.5 mg · h/liter; n ϭ 13). In spite of high protein binding, no dose modification is necessary in patients receiving continuous venovenous hemodiafiltration with AN69 membranes. A dose elevation may, however, be justified in certain cases. (This study has been registered at ClinicalTrials.gov under identifier NCT02651038.)

Elimination of fluconazole during continuous renal replacement therapy. An in vitro assessment

“…8,44 However, in vitro studies evidencing adsorption of echinocandins, including micafungin, caspofungin, and anidulafungin were recently reported. 9,36 Regarding the body of knowledge, there is a strong discrepancy when comparing conclusions drawn from in vitro to those collected in vivo, [45][46][47] at least for echinocandins. 9,36 The assessment of adsorption using in vitro studies is hampered by the great variety of methods presently used.…”

Elimination of Doripenem during Dialysis and Pharmacokinetic Evaluation of Posthemodialysis Dosing for Patients Undergoing Intermittent Renal Replacement Therapy

“…The filter clearance was calculated based on pre-and postfilter concentrations by using previously published formulae (16,28), as follows: CL pre/post ϭ (C pre Ϫ C post corr )/C pre ϫ BFR ϫ (1 Ϫ Hct) and C post corr ϭ C post ϫ (BFR Ϫ FRR)/BFR, where BFR is the blood flow rate, C pre is the doripenem plasma concentration measured at the hemofilter inlet, C post is the doripenem concentration at the hemofilter outlet, FRR is the fluid removal rate during hemodialysis, and Hct is the hematocrit value of the blood.…”

Recommendation of Antimicrobial Dosing Optimization During Continuous Renal Replacement Therapy

“…No caspofungin dosing adjustment is necessary for patients undergoing either form of CRRT (Roger et al, 2017b). Recent studies report different proportions of echinocandins lost by filter adsorption (Vossen et al, 2017). Unlike caspofungin, micafungin is not administered in a loading dose.…”