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.