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Significance of biomarkers in stewardship program in pediatric patients infected with Aspergillus species | Italian Journal of Pediatrics


A total of 73 children with proven and probable IA were entered in this study. The mean age of patients was 5 years (range:10 months to > 18 years) and the male to female ratio was 39/34 (53.4%/46.6%). Hematologic disorders were the most predisposing factors 52 (71.2%) and the lung was the most site of infections (38/73, 52%). Forty-three patients (58.9%) had received antifungal agents as prophylaxis or the treatment of previous fungal infections (Table 1).

Table 1 Clinical characteristics of the pediatric patients with invasive aspergillosis in Shiraz, southern Iran

Aspergillus species were isolated from clinical samples of 42 patients. Eleven Aspergillus fumigatus were isolated from the bronchoalveolar lavage fluids, sputum, and central nervous system, 28 Aspergillus flavus from sputum, sinuses tissue, and bronchoalveolar lavage fluids, and three Aspergillus niger from sputum and bronchoalveolar lavage fluids. 255 sera from 18 healthy volunteers (n = 36) and 73 patients suffering from probable and proven IA (n = 219) were entered into the study. Galactomannan and PCR were positive in the study population.

The median (interquartile range 1 and 3, IQR) values of sTREM-1, PCT, CRP, ESR, LDH, and WBC count in patients were 291.2 (124.8, 1286.8) pg/ml, 362.4 (185.6, 768.8) pg/ml, 29 (5–105) mg/L, 35 (18, 70) mm/h, 562 (235, 854) U/L, and 6590 (1500, 9800) cells/ml, respectively (Fig. 1). Table 2 presents the area under the curve (AUC), cut-off values, sensitivity, specificity, positive predictive values and negative predictive values of biomarkers in infected pediatric patients. The cut-off values (sensitivity, specificity) for sTREM-1, PCT, LDH, CRP, ESR, and WBC count in patients were observed > 190 pg/mL (71.2%, 100%), > 260 pg/mL (80.8%, 100%), > 252 U/l (91.8%, 100%), > 7 mg/l (90.4%, 100%), > 23 mm/h (83.6%, 94.4%), and ≤ 4930 cells/l (49.3%, 100%), respectively. The AUC (95% confidence interval) for each biomarker were 0.9 (0.85% to 0.97%) for LDH, 0.8 (0.75% to 0.84%) for PCT, 0.9 (0.85% to 0.94%) for CRP, 0.8 (0.73% to 0.85%) for ESR, 0.7 (0.6% to 0.8%) for sTREM-1, and 0.5 (0.45% to 0.58%) for WBC count (Fig. 2). There was a significant relationship between sTREM-1 and PCT (p = 0.001), and CRP values (p = 0.02) in diagnosis of IA and all of these biomarkers elevated during infection. In this study 43 patients received antifungal agent as prophylaxis or treatment of previous fungal infections (Fig. 3). The ESR, CRP and sTREM-1 values were increased and WBC count decreased in patients using antifungal agents. During the study period, 20 patients died (27.4%). The LDH and sTREM-1 level were significant increase in died patient (p < 0.05) (Fig. 4).

Fig. 1

Median of biomarkers in patients suffering from invasive aspergillosis

Table 2 The area under the curve (AUC), cut-off values, sensitivity, and specificity for biomarkers invasive aspergillosis cases
Fig. 2
figure 2

Receiver operating characteristics curves for evaluating the diagnostic role of biomarkers in patients with invasive aspergillosis

Fig. 3
figure 3

A comparison chart of evaluated biomarkers in patients who have received antifungal agents and those who have not

Fig. 4
figure 4

A comparison chart of evaluated biomarkers in living and dead patients



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