Clinical features in proven and probable invasive fungal disease in children and adolescents at a pediatric referral center: a 5-year experience

Abstract Background Children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) are at high risk for invasive fungal disease (IFD). Methods This multicenter, randomized, open-label trial planned to enroll 560 children and adolescents (3 months to <21 years) undergoing allogeneic HCT between April 2013 and September 2016. Eligible patients were randomly assigned to antifungal prophylaxis with caspofungin or a center-specific comparator triazole (fluconazole or voriconazole). Prophylaxis was administered from day 0 of HCT to day 42 or discharge. The primary outcome was proven or probable IFD at day 42 as adjudicated by blinded central review. Exploratory analysis stratified this evaluation by comparator triazole. Results A planned futility analysis demonstrated a low rate of IFD in the comparator triazole arm, so the trial was closed early. A total of 290 eligible patients, with a median age of 9.5 years (range 0.3–20.7), were randomized to caspofungin (n = 144) or a triazole (n = 146; fluconazole, n = 100; voriconazole, n = 46). The day 42 cumulative incidence of proven or probable IFD was 1.4% (95% confidence interval [CI], 0.3%–5.4%) in the caspofungin group vs 1.4% (95% CI, 0.4%–5.5%) in the triazole group (P = .99, log-rank test). When stratified by specific triazole, there was no significant difference in proven or probable IFD at day 42 between caspofungin vs fluconazole (1.0%, 95% CI, 0.1%–6.9%, P = .78) or caspofungin vs voriconazole (2.3%, 95% CI, 0.3%–15.1%, P = .69). Conclusions In pediatric HCT patients, prophylaxis with caspofungin did not significantly reduce the cumulative incidence of early proven or probable IFD compared with triazoles. Future efforts to decrease IFD-related morbidity and mortality should focus on later periods of risk. Trial Registration NCT01503515.

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Epidemiology and Clinical Features of Invasive Fungal Disease in a US Healthcare Network

Open Forum Infectious Diseases ◽

10.1093/ofid/ofx163.029 ◽

2017 ◽

Vol 4 (suppl_1) ◽

pp. S83-S83 ◽

Cited By ~ 1

Author(s):

Brandon Webb ◽

Jeffrey Ferraro ◽

Susan Rea ◽

Jennifer Kammerer ◽

Stephanie Kaufusi ◽

...

Keyword(s):

Clinical Features ◽

Invasive Fungal Disease ◽

Fungal Disease ◽

Global Development ◽

Research Support ◽

Dimorphic Fungi ◽

Healthcare Network ◽

Novel Method ◽

Intermountain Healthcare ◽

Spectrum Of Patients

Abstract Background A better understanding of the epidemiology and clinical features of invasive fungal disease (IFD) is integral to improving outcomes. Here we aimed to describe the incidence, clinical features and outcomes of IFD in a large US healthcare network. Methods We developed a novel method of IFD cohort discovery to query all available records in the Intermountain Healthcare electronic data warehouse from 2006 to 2015 for clinical data associated with IFD (Figure 1). Resulting data were overlaid in 124 different combinations to identify high-probability IFD cases. The cohort was manually reviewed and exclusions applied. EORTC/MSG definitions were adapted to categorize IFD in a broad patient population. Linear regression was used to model variation in incidence over time. Results 3,391 IFD episodes occurred in 3,171 patients. Mean incidence was 27.4 cases/100,000 patients per year (Figure 2). Estimated mean annual increase was 0.24 cases/100,000 patients (r2 = 0.09, P = 0.21). Candidiasis was most common (56%). Dimorphic fungi, primarily Coccidioides, comprised 24%, followed by aspergillosis (9%). Mean age was 50 years; pediatric cases accounted for 13%. 19.2% of patients had an active malignancy or primary immunodeficiency, 6.9% were transplant recipients, and 27.5% were on immunosuppression. Lymphopenia preceded IFD in 24.4% of patients. Hospital admission occurred in 75%; median length of stay was 12 days. All-cause mortality was 17% at 42 days and 28.6% at 1 year. 42-day mortality was highest in aspergillosis (27.5%), 20.5% for Candida, and lowest for dimorphic fungi (7.5%). Conclusion In this population, IFD was not uncommon, affected a broad spectrum of patients and had high observed mortality. Disclosures B. Webb, Astellas Pharma Global Development, Inc.: Grant Investigator, Research grant. J. Ferraro, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. S. Rea, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. J. Kammerer, Astellas Pharma Global Development, Inc..: Employee, Salary. S. Kaufusi, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. B. Goodman, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. G. Martin, Astellas Pharma Global Development, Inc.: Grant Investigator, Research support. J. Spalding, Astellas Pharma Global Development, Inc.: Employee, Salary

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