Characterizing Safety and Clinical Outcomes Associated with High-Dose Micafungin Utilization in Patients with Proven Invasive Candidiasis.

Victoria C Grant,Anna Y Zhou,Karen K Tan,Sasha Rodriguez,Jacinda C Abdul-Mutakabbir,Kenneth Nguyen

doi:10.3390/tropicalmed7020023

Abstract

Micafungin is the empiric antifungal agent of choice for the treatment of invasive candidiasis (IC). Pathophysiologic changes that occur in obese and/or critically ill patients can alter micafungin serum concentrations and the probability of target attainment. Although high doses of micafungin have been shown to be safe, clinical outcomes have not been widely evaluated. We conducted a single-center, retrospective observational study evaluating safety and clinical outcomes among adult patients treated with ≥200 mg of micafungin for ≥3 days for proven IC from 1 September 2013 through 1 September 2021. Twenty-three unique encounters for 21 patients were evaluated. The median BMI and APACHE II scores were 37.1 (IQR 28.8–48.9) and 24 (IQR 17.7–31), respectively. The median average daily dose of micafungin was 300 mg (IQR 275–400). Patients were treated with high-dose (HD) micafungin for the entirety of their echinocandin course in 15 encounters (65.2%). Transaminases remained stable, while a trend towards increased alkaline phosphatase was observed. A total of four deaths occurred (17.4%). Patients that died were predominantly young, Hispanic males who were obese and/or critically ill. Future studies are needed to determine the necessity and appropriate placement of HD micafungin in obese and/or critically ill patients.

Highlights

Invasive candidiasis (IC) is an increasing healthcare concern in the United States (US)and candidemia is one of the most common healthcare-associated bloodstream infections [1]
Recent studies have evaluated the pathophysiologic changes that occur in obese and/or critically ill patients and found that these changes may alter the pharmacokinetics of micafungin, subsequently altering serum concentrations and the probability of target attainment (PTA) [7]
The most common comorbid condition was diabetes mellitus and the most common risk factor for developing IC was the presence of an indwelling central line

Summary

Introduction

Invasive candidiasis (IC) is an increasing healthcare concern in the United States (US)and candidemia is one of the most common healthcare-associated bloodstream infections [1]. In the subgroup of patients with candidemia, the rate of mortality was higher and reported as 28% [2]. Echinocandins are the empiric antifungal agents of choice for the treatment of IC and are recommended as the first-line definitive therapy for infections due to select Candida species (i.e., Candida krusei) [5]. Micafungin is approved by the US Food and Drug Administration at doses of 100–150 mg (referred to as conventional doses throughout this paper) for the treatment of candidemia, IC (excluding meningoencephalitis, ocular dissemination, endocarditis, and osteomyelitis), and esophageal candidiasis [6]. Recent studies have evaluated the pathophysiologic changes that occur in obese and/or critically ill patients and found that these changes may alter the pharmacokinetics of micafungin, subsequently altering serum concentrations and the probability of target attainment (PTA) [7]. It has previously been demonstrated that the area under the curve:minimum inhibitory concentration (AUC:MIC) ratio is the most appropriate pharmacodynamic target for micafungin [8]

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