Evaluation of clinical characteristics, treatment, and prognosis in invasive fungal infections in children

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). Keywords: Invasive fungal diseases, yeast, mold, children