Invasive Candida species disease in infants and children: occurrence, risk factors, management, and innate host defense mechanisms

Invasive infections by opportunistic Candida species significantly impact morbidity and mortality. This review provides an update of the incidence, risk factors, and management of invasive candidal disease in infants and children, focusing on very-low-birth-weight neonates, and highlights recent advances in understanding candidal virulence factors and innate anti-Candida species host defense mechanisms. Invasive infections with Candida species are the most common cause of late-onset, blood culture-proven nosocomial sepsis in very-low-birth-weight neonates. Risk factors include colonization, long stay in neonatal intensive care units, and use of broad-spectrum antibiotics, central venous catheters, parenteral nutrition, and mechanical ventilation. These risks are compounded by increasing resistance of Candida species to standard antifungal agents. Recent data suggest that, in addition to the macrophage mannose receptor, beta-glucan receptors, Toll-like receptors, and galectin-3 play an important role in host recognition of Candida species. Reduction of proven risk factors, more aggressive eradication of colonizing fungi by anticandidal agents, and possibly Candida species vaccines may reduce Candida species-associated morbidity and mortality. Accumulating data of molecular mechanisms that underlie innate immune functions against Candida species may provide a basis to prevent and treat candidal infections more efficiently.