Addressing the silent threat: managing invasive Candida infections in hospitalized newborns

Abstract

Invasive fungal infections (IFIs) remain an important problem for hospitalized newborn infants receiving intensive care, given their substantial morbidity and mortality. Candida species (Candida spp.) are the major fungal pathogens, which cause the so-called invasive Candida infections (ICIs). Of these, Candida albicans is the most commonly isolated species, followed by Candida parapsilosis. Other identified Candida spp. include Candida glabrata, Candida tropicalis, Candida krusei, etc. However, an increasing shift in the epidemiology of ICIs worldwide has been described, non-albicans Candida (NAC) spp. ICIs pose a growing threat to neonates. Herein, we examine the epidemiology of Candida spp. infections, patterns of antifungal resistance, risk factors, prevention strategies, clinical outcomes, and treatment recommendations for ICIs in hospitalized newborn infants. This review aims to provide a thorough understanding of the current evidence on ICIs to better inform targeted prevention strategies and improved treatments to reduce neonatal morbidity and mortality.

Keywords: antifungal resistance; invasive Candida infections (ICIs); newborn infants; pathogens; prevention strategies; risk factors; treatments.

Figure 1

Potential risk factors for the incidence of invasive Candida infections (ICIs). (A) Preterm birth and low birth weight. Gestational age and birth weight are key risk factors for ICIs, with incidence inversely related to both. (B) Broad-spectrum antibiotics use. Prolonged use of broad-spectrum antibiotics, especially third-generation cephalosporins (TGCs) and carbapenems, suppresses normal flora, allowing fungi to colonize mucosal niches and facilitating subsequent invasion and spread. (C) Central Venous Catheters (CVCs). CVCs penetrate epithelial barriers, facilitating colonization of catheter tips and progression to ICIs. (D) Type and number of sites colonized by fungi. Multiple sites (≥3) or special sites (e.g., urine, catheters) colonized by Candida spp. are associated with a higher risk of ICIs. (E) Gastrointestinal disorders. Gastrointestinal disorders, including congenital anomalies, as well as necrotizing enterocolitis (NEC), intestinal perforation, previous abdominal surgeries, and the presence of stomas in any location, predispose cases to ICIs. (F) Other potential risk factors. Other potential host risk factors include vaginal birth, lower Apgar score at 5 min, length of NICU stay >7 days, thrombocytopenia, neutropenia, etc. (G) Other potential medical intervention-related risk factors. Related risk factors also include parenteral nutrition, corticosteroid use, H2 antagonists, and other potential invasive devices, such as endotracheal tubes, drains, urinary catheters, extracorporeal membrane oxygenation (ECMO), etc. (Created in BioRender.com).