METHODS
STUDY DESIGN AND POPULATION
Clinical data of all pediatric patients (0–18 years) diagnosed with IFD at the PHOU of the Hospital General Universitario Gregorio Marañón (HGUGM) from January 2006 to December 2019 were retrospectively reviewed. HGUGM is a tertiary hospital located in Madrid (Spain) with 120 pediatric beds and around 7 000 pediatric inpatient admissions per year. The PHOU of HGUGM has experienced a rising activity in recent years, due in part to the creation of an adolescent unit and the accreditation as a national reference center for hereditary erythropathologies. Admissions in the PHOU have progressively increased from 343 in 2006 to 853 in 2019.
Information collected from the patients who met the inclusion criteria included: demographics, underlying condition, IFD host factors, antifungal prophylaxis (AFP), laboratory, microbiological and radiological findings, antifungal therapy and clinical outcome. Deaths observed during the IFD treatment-period were analyzed.
DEFINITIONS
Cases were defined as proven, probable and possible IFD based on the last update of the consensus definitions of IFD from the EORTC/MSGERC. Proven disease required histopathologic or microbiologic documentation of infection from tissue obtained by biopsy or autopsy, or an isolation from a culture sample obtained from a normally sterile site. Probable disease was defined as the presence of host factors, clinical features and mycological evidence of an IFD. Possible disease required only proper host factors and sufficient clinical evidence compatible with IFD3.
Host factors for IFD were those defined by the EORTC/MSGERC consensus: a recent history of prolonged neutropenia (<500 neutrophils/µL for >10 days), hematologic malignancy, allogeneic HSCT or solid organ transplant, prolonged use of corticosteroids (≥0.3 mg/kg for ≥ three weeks in the past 60 days), treatment with B-cell o T-cell immunosuppressants, severe hereditary immunodeficiency and graft-versus-host disease (GVHD)3.
The risk for IFD represented the probability of IFD for each underlying condition. Patients at high-risk (≥10%) for IFD were those with acute myeloid leukemia (AML), relapsed or refractory acute lymphoblastic leukemia (ALL), severe aplastic anemia, myelodysplastic syndrome or those who underwent an allogeneic HSCT or developed a GVHD. Patients with non-Hodgkin lymphoma, standard-risk ALL or autologous HSCT were considered low-risk (≤5%) for IFD. In contrast, patients with solid organ tumors (SOT), like brain tumors or Hodgkin lymphoma, were classified as sporadic risk9,10. IFD prevalence was calculated by dividing the number of cases of IFD by the total number of patients at risk. Moreover, the ratio of cases of IFD per 1 000 admissions in the PHOU was calculated globally and by time periods.
ETHICS
We conducted this study in accordance with the Declaration of Helsinki and its subsequent amendments. No personal or identifiable data were collected. Ethics approval was obtained from the Clinical Research Ethics Committee at HGUGM.
STATISTICAL ANALYSES
Descriptive analyses were performed using frequencies and proportions for categorical variables and medians and interquartile ranges (IQR) for continuous variables. Comparative analyses were conducted according to the type of infection (yeast vs. mold infections), time periods (equally divided into three 56-months periods: January 2006 to August 2010 vs. September 2010 to April 2015 vs. May 2015 to December 2019) and outcome (survivors vs. non-survivors). Categorical variables were compared using the chi-square or the Fisher exact test, as appropriate. Continuous dicotomic variables were evaluated with the Mann-Whitney U test. Kruskal-Wallis test, followed byposthoc analyses, was used when comparing variables among the three time periods. Statistical analyses were performed using IBM SPSS Statistics software (Statistical Package for the Social Sciences) version 23.0. The statistical significance level was defined as a two-tailed p- value <0.05.