Significance of biomarkers in stewardship program in pediatric patients infected with Aspergillus species

Abstract

Background The potential use of biomarkers in the diagnosis of fungal infections is a challenge. The aim of this study was to evaluate the role of a biomarker-guided antifungal stewardship program for hospitalized pediatrics suffering from invasive aspergillosis (IA). Methods Pediatric patients with suspected probable or proven IA were enrolled in this study. Demographic data were collected from their records. Clinical samples were examined by wet mount KOH smear, culture, galactomannan Ag test, and real-time PCR. Patients’ sera were evaluated for procalcitonin (PCT) and soluble-triggering receptor expressed on myeloid cells -1 (sTREM-1) levels by ELISA Kits. Results A total of 73 children were entered in this study with a mean age of 5 years and the male to female ratio 39/34. The most predisposing factors were hematologic disorders (71.2%). The area under the curves (95% confidence interval) for each biomarker were 0.9 (0.85% to 97%) for lactate de hydrogenase (LDH), 0.9 (0.85% to 0.94%) for C-reactive protein, 0.8 (0.75% to 0.84%) for PCT, 0.8 (0.73% to 0.85%) for erythrocyte sedimentation rate, 0.7 (0.6% to 0.8%) for sTREM-1, and 0.5 (0.45% to 0.58%) for white blood cell count. During the study period, 27.4% patients died. The LDH and sTREM-1 levels were significant increase in died patient (p < 0.05). Conclusions According to our data, evaluation of biomarkers along with radiologic and clinical signs and symptoms of pediatric patients can lead to proper antifungal therapy and decreased side effects, antifungal resistance, and cost. The combined measurements could be better than a single marker in the prediction of IA.

Role of biomarkers in the diagnosis of invasive aspergillosis in immunocompromised patients

“…Unfortunately, there are limited data in the literature about the role of the PCT level as a diagnostic marker for IA. The cut-off value for PCT > 260 pg/mL with a sensitivity of 80.8% and specificity of 100% was reported in pediatric patients suffering from IA [ 27 ]. In Robinson et al, after 3 days, a PCT level > 500 pg/mL occurred in 81% (17/21) of the patients with invasive fungal diseases [ 28 ].…”

“…Buckland et al reported circulating sTREM-1 levels in experimental fungal asthma peaked on day 30 in the mice model [ 35 ]. The cut off value for sTREM1 > 190 pg/mL with sensitivity 71.2%, specificity 100%, PPV 100% and NPPV 46.2% was reported in infected pediatric patients with Aspergillus species [ 27 ]. In the literature, we could not find a study that included the cut-off value of sTREM-1 in patients suffering from IA.…”

“…In the present study, the AUC of CRP was higher than that of other biomarkers. The cut-off value for CRP > 7 mg/l with a sensitivity of 90.4% and specificity of 100% was reported were reported in patients with IA [ 27 ]. Lactate dehydrogenase is an enzyme required for energy production for human cells and is released into the bloodstream during cell damage.…”

“…Ling Cheng and co-workers by ROC curve analysis reported that PCT concentrations of more than 1.31 ng/mL increased the incidence of a voriconazole trough level higher than 5 µg/mL [ 43 ]. The ESR, CRP, and sTREM-1 values in pediatric patients with IA were increased in patients using antifungal agents [ 27 ]. A decrease in biomarkers in patients using antifungal agents presents the effectiveness of treatment [ 44 ].…”