Çocuklarda invazif mantar enfeksiyonları: Klinik özellikler, tedavi ve prognozun değerlendirilmesi.
Özet
Azer Karaman, Evaluation of clinical characteristics, treatment, and prognosis in invasive fungal
infections in children. Specialist Thesis, Department of Pediatrics, Faculty of Medicine, Hacettepe
University, Ankara, 2024. Invasive fungal diseases is one of leading causes of morbidity and mortality
in immunocompromised children. Despite its clinical significance, very few studies have been
conducted on invasive fungal infections in children in our country. It is crucial to determine the mortality
rate associated with invasive fungal diseases, the fungi and species causing it, as centers generate their
own data and continue surveillance studies. This study aims to determine the clinical characteristics,
radiological features, risk factors, prognosis, and factors influencing mortality in children observed in
our center over a 12-year period. Furthermore, determining distribution of fungal species (yeast or
mold), antifungal-resistance species and identification of antifungal drugs used were aimed. For this
purpose, demographic, laboratory, disease and treatment course characteristics of pediatric patients with
invasive fungal disease (aged 1 month to 18 years), who were followed up at Hacettepe University Ihsan
Dogramaci Children's Hospital between years 2010 and 2022 were retrospectively analyzed. A total of
254 pediatric patients with invasive fungal disease were identified. Patients were categorized based on
classification of invasive fungal diseases as "proven", "probable" and "possible", according to the
criteria specified by the European Confederation of Medical Mycology and the Mycoses Study Group
Education and Research Consortium of the European Organization for Research and Treatment of
Cancer and Mycoses Study Group, as well as the 2019 update from the National Allergy and Infectious
Diseases Institute Fungal Diseases Working Group. Among 254 patients, 167 patients (65.7%) were
diagnosed with invasive yeast infection, while 87 patients (34.3%) had invasive mold infection. 170
patients (66.9%) were categorized as "proven", 61 patients (24%) as "probable” and 23 patients (9.1%)
as “possible”. 166 patients (65.3%) had candida, 79 patients (31.1%) had aspergillus, 6 patients (2.4%)
had mucorales, 2 patients (0.8%) had fusarium, and 1 patient (0.4%) had malassezia infection. The most
common underlying disease in the yeast group was genitourinary system anomaly or disease (15.6%),
while in the mold group, it was acute lymphoblastic leukemia (23%). At diagnosis, neutropenia (58.6%)
was more prevalent and the CRP value was higher (11.72±11.79 mg/dl, p<0.05) in patients with invasive
mold infection. The sensitivity of galactomannan in patients with confirmed aspergillus infection was
determined to be 33.3% (13/39). Among 67 patients with a positive thoracic CT scan, nodules were
observed in at least one in 61 patients (91%). In patients with radiologically proven central nervous
system involvement of disease with cranial MRI, most common radiological finding was hemorrhagic
infarction (40%). Forty different species of Aspergillus species were detected in 39 patients (15.3%);
with Aspergillus fumigatus being the most commonly identified (47.5%). 169 different species of
candida were isolated from 163 patients; C. albicans was the most prevalent among them (45%). In the
yeast patient group, fluconazole (38.2%) and caspofungin (56.9%) were preferred, whereas in the mold
patient group, amphotericin-B (85.1%), voriconazole (59.8%), micafungin (3.4%), and combined usage
(65.5%) rates were higher (p<0.05). The treatment of 56 patients (22%) was discontinued due to death,
and the treatment of 2 patients (0.8%) was not completed due to other reasons. Mortality rate was
15.6% in the yeast group and 34.5% in the mold group. Among patients with invasive mold disease,
those in whom treatment could not be completed due to death, had a higher CRP value at diagnosis
(p<0.05). Resistance to 18 antifungal agents was found in 15 patients. The highest prevalence of
antifungal resistance was observed with fluconazole (61.1%), compared to other antifungal agents. In
the 28 days prior to diagnosis, higher incidences of central catheter presence (82.0%), urinary catheter
presence (12.0%), past invasive mechanical ventilation (26.9%), past surgery (26.3%), admission to the
intensive care unit (31.7%) and bacterial infection (46.7%) were observed in the yeast group.
Conversely, patients with invasive mold infection showed significantly greater recent use of
immunosuppressive therapy (69%) and a higher incidence of neutropenia (56.3%) (p<0.05). The 7-day
survival rate for the entire group was 95.7%, while the 30-day survival rate was 83.1%. The survival
rate after 30 days was higher in patients who were not septic at the time of diagnosis, both in the mold
and yeast groups (p<0.05). In the yeast group, patients without a history of mechanical ventilation or
quinolone treatment or central catheter presence had significantly higher survival rates after 30 days
(p<0.05). In the mold group, patients without a history of immunosuppressive or quinolone treatment
had significantly higher survival rates after 30 days (p<0.05). Among yeast group, patients who did not
survive into 30th day had a significantly longer pre-diagnosis hospitalization (42.35 days; p<0.05).
