ONE FOR THE MONEY, TWO FOR THE ECMO: A SUCCESSFUL PHARMACOTHERAPEUTIC STRATEGY FOR VANCOMYCIN-RESISTANT ENTEROCOCCUS FAECIUM AND CANDIDA GLABRATA FUNGEMIA IN VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION AND CONTINUOUS RENAL REPLACEMENT

Abstract

SESSION TITLE: Fellows Critical Care Posters SESSION TYPE: Fellow Case Report Posters PRESENTED ON: October 18-21, 2020 INTRODUCTION: Extracorporeal membrane oxygenation (ECMO) and continuous renal replacement therapy (CRRT) are modalities with a relative paucity in understanding of the disposition of antimicrobials, and even less for when used simultaneously. Preliminary investigations have demonstrated that ECMO leads to pharmacokinetic changes, which include alterations in volume of distribution, drug clearance, and sequestration by the circuit.1 CASE PRESENTATION: Our patient was a 66-year-old-male with a history of alcohol use disorder, transferred to our hospital for acute respiratory distress syndrome due to influenza A pneumonia with superimposed bacterial pneumonia, cannulated for venous-venous ECMO. Encephalopathy, atrial fibrillation, pulmonary embolisms, distributive shock, and anuric acute kidney injury requiring CRRT complicated his course. Following a prolonged course, blood cultures were obtained and Candida glabrata and vancomycin resistant Enterococcus faecium (VRE) were isolated. We initiated high dose micafungin 150 mg IV q 24 h, high dose, high frequency daptomycin 10 mg/kg IV q 24 h. An echocardiogram, Ophthalmology consult, and repeat blood cultures were also requested to document clearance of fungemia and bacteremia. A trans-esophageal echocardiogram was performed, without evidence of masses or vegetations. Fundal exam did not show any signs of fungal endophthalmitis. Repeat cultures were without growth, all existing IV lines were exchanged except for ECMO cannulas. His leukocytosis began to downtrend, and he became afebrile after start of antimicrobial therapy. Given that his most likely source of infection was line associated, a two-week antimicrobial course for uncomplicated fungemia and bacteremia was recommended. DISCUSSION: We hope to add to the limited data on daptomycin and micafungin dosing strategies for patients on ECMO and CRRT. A thorough understanding of the altered pharmacokinetics is essential to apply in these complex patients. Daptomycin has a low volume of distribution, and it is highly protein bound, making it less likely to be affected by ECMO. It is known that for patients on CRRT, daptomycin dosing q 24 h up to 12 mg/kg provides comparable drug exposure to patients with a CrCl = 30 mL/min,2 therefore, a dose of 10 mg/kg q 24 h was deemed appropriate to treat our patient. Creatinine kinase was monitored weekly without any changes from baseline. Micafungin is highly protein bound, minimally renally cleared and does not require CRRT dose adjustment. CONCLUSIONS: Prior studies in ECMO patients have shown decreased plasma concentrations due to drug degradation and increased clearance,3 which warrant a dose increase. As such, micafungin 150 mg q 24 h was used in our patient. This report highlights the need for more research on optimal dosing strategies of antimicrobials in this patient population. Reference #1: Cheng V, Abdul-Aziz MH, Roberts JA, Shekar K. Optimising drug dosing in patients receiving extracorporeal membrane oxygenation. J Thorac Dis. 2018;10(Suppl 5):S629-S641. Reference #2: Xu X, Khadzhynov D, Peters H, et al. Population pharmacokinetics of daptomycin in adult patients undergoing continuous renal replacement therapy. Br J Clin Pharmacol. 2017;83(3):498-509. Reference #3: Watt KM, Cohen-Wolkowiez M, Williams DC, et al. Antifungal extraction by the extracorporeal membrane oxygenation circuit. J Extra Corpor Technol. 2017;49(3):150-159. DISCLOSURES: No relevant relationships by M. Gabriela Cabanilla, source=Web Response No relevant relationships by Nicholas Villalobos, source=Web Response