Role of (1,3)-β-D-glucan in early diagnosis of invasive fungal infections in preterm neonates admitted in neonatal intensive care unit

Rationale: Invasive fungal infections are the important contributor to neonatal morbidity and mortality. Immunocompromised hosts, such as premature infants, with invasive candidiasis can suffer from severe and life-threatening illness. The incidence of invasive candidiasis in extremely low birth weight infants varies by neonatal intensive care unit (NICU) from 10% to 28%. The most commonly reported risk factors for invasive fungal infection are prematurity, low birth weight, major congenital malformations, exposure to broad spectrum antibiotics, central venous catheters, delayed enteral feeds, prolonged parenteral nutrition, endotracheal intubation, and longer NICU stay. Invasive fungal infection manifestations are non-specific, and blood culture is considered the gold standard for its diagnosis. Unfortunately, the results of blood cultures are usually obtained after 48 h or more. More-over, there are high rate of false negative results with cultures. Therefore, new tools are required for early diagnosis of invasive fungal infection in neonates. 1,3-β-D-Glucan (BDG) is a component of the outer cell wall of fungi, including Candida spp., and it is released into the blood stream during invasive fungal infection. To date, only few trials have been conducted regarding performance of 1,3-β-D-Glucan as diagnostic marker of invasive fungal infection in Indian neonates. Novelty: Culture-based diagnostic media have a recognized and clear role in the diagnosis of invasive fungal infections but their deficiencies are also known, particularly in sensitivity and also in speed. Therefore, it is essential to implement the diagnosis of invasive fungal infections with non-culture-based techniques. One of the biomarkers targeting specific Candida fungal components is 1,3-β-D-glucan (BDG) which is a constituent of the cell wall of many fungi and can be detected in the serum during invasive fungal infection.  However, there is paucity of data regarding the performance of this technique in Indian neonates. Objectives: To evaluate the performances of (1,3)-β-D-glucan for the diagnosis of invasive fungal infections and to compare its diagnostic value with blood culture for the diagnosis of invasive fungal infections in preterm neonates admitted in neonatal intensive careunit. Methods: Preterm neonates admitted in NICU having suspected fungal sepsis (birth weight <1250 g, history of broad-spectrum antibiotic or a third-generation cephalosporin coverage > 7 days, platelet count <150,000/µL, enteral feeding by 3 days of life, use of systemic steroids > 3 days, invasive mechanical ventilation

3 days, total parenteral nutrition >5 days, Central catheter, and length of NICU stay >7 days) will be enrolled in the study. Two samples of whole blood will be collected from each neonate. One sample for blood culture transported to microbiology department for automated BACTEC culture and clinical isolates of Candida spp. will be obtained from blood culture. Serum will be separated from second sample by centrifugation and the BDG assay will be done immediately or sub-pack for cryopreservation at -20°C or -80°C. Measured outcomes: Diagnostic efficacy of (1,3)-β-D-glucan will be compared with blood culture for the diagnosis of invasive fungal infections in preterm neonates admitted in neonatal intensive care.