By Stan Deresinski, MD, FACP

Clinical Professor of Medicine, Stanford University

SYNOPSIS: A review of a national administrative database examined 703 patients with Candida endocarditis and found the greatest risk factor for mortality was underlying liver failure, while a history of opiate abuse was associated with a reduced risk of death.

SOURCE: Huggins JP, Hohmann S, David MZ. Candida infective endocarditis: A retrospective study of patient characteristics and risk factors for death in 703 United States cases, 2015-2019. Open Forum Infect Dis 2020;8:ofaa628.

Using the nationwide Vizient database, Huggins and colleagues retrospectively examined information regarding 703 inpatients with Candida endocarditis seen at 179 clinical sites from Oct. 1, 2015, through April 30, 2019. The median number of cases per site was five (range, 1-32), and 57.2% were male.

Diabetes was present in 28.6% of patients, and 31.2% had chronic kidney disease, with 10.4% of the total cohort receiving hemodialysis. Only 14 patients (2.2%) were human immunodeficiency virus-infected, while 22 (3.1%) had undergone solid organ transplantation, and 31 (4.4%) had hematologic malignancy in either the present or the past. Hepatitis C virus infection was documented in 199 patients (27.0%), and hepatitis B virus infection was documented in 20 patients (2.8%). Fifty-five patients (7.8%) had acute or subacute liver failure, and 25 (3.6%) had documented cirrhosis. Present or past opioid abuse was documented in 213 cases (30.3%), while there was a history of use of other illicit substances in 128 cases (18.2%).

A valve procedure was performed on 158 patients (22.5%) during their hospitialization, with no significant difference in mortality in those who did so (23.1%) and those who did not (19.3%; P = 0.370). Approximately one-third of procedures each involved the aortic and tricuspid valves, while in one-eighth the mitral valve was addressed. Intervention involved more than one valve in 17.1%. Almost all aortic valve and mitral valve interventions (98% and 90%, respectively) involved replacement procedures, while only 80.8% of those involving the tricuspid valve resulted in valve replacement.

Most patients received an echinocandin or fluconazole, and both were received together in 28.6%. The mortality rate prior to discharge was 16.2%. The strongest independent predictor of death was liver failure. In an adjusted analysis, a number of other predictors were associated with mortality risk, while opiate abuse was associated with a lower risk (odds ratio [OR], 0.5; 95% confidence interval [CI], 0.2 to 0.9).

COMMENTARY

This study has many of the drawbacks to be predicted when the information is limited to that in an administrative database. Examples include lack of clear insight into the proportion of cases that might have involved prosthetic cardiac valves, lack of information on the Candida species involved, and limited insight into the precise courses of antifungal therapy.

The 2016 guideline of the Infectious Diseases Society of America recommends administration of a lipid formulation of amphotericin B with or without flucytosine, or the use of an echinocandin in high dose (caspofungin or micafungin 150 mg daily, anidulafungin 200 mg daily), with subsequent transition to fluconazole (depending on in vitro susceptibility).1 The guideline also states that “valve replacement is recommended.”

Something of note from the experience reviewed here is that the presence of liver failure was the strongest predictor of mortality. Unfortunately, there is no information regarding the direct cause of death in those patients. Also of note is the lesser mortality associated with illicit drug use, which is fortunate since the current opiate abuse epidemic in the United States has been reported to be associated with an increased frequency of Candida endocarditis cases. It could be speculated that this apparent lesser mortality may be associated with younger age and also the greater frequency of tricuspid valve infection.

REFERENCE

  1. Pappas PG, Kauffman CA, Andes DR, et al. Executive Summary: Clinical Practice Guideline for the Management of Candidiasis: 2016 Update by the Infectious Diseases Society of America. Clin Infect Dis 2016;62:409-417.