**2. Epidemiology and incidence of neonatal invasive fungal infections**

Neonates represent a unique and highly vulnerable patient population. Advances in medical technology have improved the survival and quality of life of newborns, particularly those with extreme prematurity or with congenital defects. Immunologic immaturity and altered cutaneous barriers play some role in increasing the vulnerability of neonates to infections. In this context, neonatal infection is a major cause of mortality and morbidity in newborns. Estimates suggest that >1.4 million neonatal deaths worldwide annually are due to invasive infections [14, 15].

The occurrence of invasive fungal infections has increased significantly worldwide, representing an important infective complication in patients hospitalized in intensive care units. Premature infants in NICUs are at particular risk of these invasive fungal infections, and unfortunately, the incidence of fungal septicemia appears to be increasing [16, 17]. In this context, *Candida* and *Malassezia* species are the most prevalent pathogen involved in fungal infections in NICU [18].

and more than 40% of these deaths occur in the neonatal period [1, 2]. These data have several causes and particularly the neonates are at high risk due to fungal infections, mainly by yeasts

In addition, species of the genus *Candida* have the capacity to inhabit several niches, thus, as part of the skin, mucosa and gastrointestinal tract [5]. Therefore, is considered that there is an association between colonization and systemic candidiasis mainly in seriously ill patients [6]. Although *Candida albicans* are more frequent, species of *Candida* non-*albicans* are also cause of diverse clinical pictures important in neonates, especially those that are in NICUs. The main Candida non-albicans species included are *Candida parapsilosis* complex, *Candida glabrata* and *Candida krusei*. However, uncommon species as *Pichia fabianii* and *Kodamaea ohmeri* may occur

The newborns clinical course in the Intensive Care Units usually complicates after the onset of fungal infections [11]. In this hospital environment, adverse events may occur due to the complexity of the patients [12]. In this sense, the treatments and procedures instituted for primary disease may be an important factor for the onset of fungal infections; birth weight between 1000 and 1500 g is also a predictive factor and a way for the clinical worsening [13]. The predisposing factors to fungal infections include prolonged use of antibacterial and use of medical devices, among other conditions that lead to fungal disease. In addition, biofilms are frequent on the surface of medical devices, being consider a negative event, since it character-

Commonly, amphotericin B, azoles and echinocandins are used for the treatment of various invasive fungal infections. However, antifungal therapeutic failures contribute to a higher mortality rate and may occur due to intrinsic resistance, so it is important to perform antifungal sensitivity tests. These tests can predict the ideal antifungal or contribute in the choice

**2. Epidemiology and incidence of neonatal invasive fungal infections**

Neonates represent a unique and highly vulnerable patient population. Advances in medical technology have improved the survival and quality of life of newborns, particularly those with extreme prematurity or with congenital defects. Immunologic immaturity and altered cutaneous barriers play some role in increasing the vulnerability of neonates to infections. In this context, neonatal infection is a major cause of mortality and morbidity in newborns. Estimates suggest that >1.4 million neonatal deaths worldwide annually are due to invasive

The occurrence of invasive fungal infections has increased significantly worldwide, representing an important infective complication in patients hospitalized in intensive care units. Premature infants in NICUs are at particular risk of these invasive fungal infections, and unfortunately, the incidence of fungal septicemia appears to be increasing [16, 17]. In this

izes greater pathogenicity and antifungal resistance of fungi.

according to the use of other medicines and the condition of the neonate [9].

of the genus *Candida* [3, 4].

110 Selected Topics in Neonatal Care

[7–10].

infections [14, 15].

The incidence of bloodstream infections due to *Candida* species in the overall population ranges from 1.7 to 10 episodes per 100,000 inhabitants. An estimated 33–55% of all episodes of candidemia occur in intensive care units and are associated with mortality rates ranging from 5 to 71% [16].

Invasive candidiasis is an important cause of sepsis in the NICU. Candida infections in infants are associated with significant mortality and morbidity, including neurodevelopmental impairment. The incidence of invasive candidiasis in NICU ranges from 2.6 to 13.2% in very low birth weight infants (1500–1000 g) and from 6.6 to 26.0% in extremely low birth weight infants (<1000 g) [19].

*C. albicans* has been the most frequently isolated species; however, infections caused by others species have been diagnosed with increased frequency. In the NICU in the 1990s, the overall incidence of candidemia increased because of the increased survival and intensive care of extremely preterm infants. During that time period, the proportion of candidemia decreased because of *C. albicans*, whereas increased because of *C. parapsilosis* [20, 21].

Invasive infections associated with *C. parapsilosis* cause fewer acute lethal events in premature newborns than systemic infections with *C. albicans*; nevertheless, *C. parapsilosis* fungemia significantly increases the morbidity and mortality of severely ill infants who require care in a NICU [22].

Laboratory studies have documented that *C. parapsilosis* is less virulent than *C. albicans*. However, the capability to adhere tenaciously to prosthetic materials forming biofilm and to proliferate rapidly in high concentrations of glucose are factors that facilitate the infection in the hospital environment. This trait may contribute to its ability to adhere to plastic catheters and cause systemic infections in premature newborns receiving total parenteral nutrition, blood pressure transducers or other invasive devices. Such a route of transmission may account for the occurrence of epidemic outbreaks of *C. parapsilosis* bloodstream infections [21].

Other emerging *Candida* species such as *C. haemuloniii*, *C. pelliculosa* and *C. tropicalis* have also been associated with infections in NICU. *C. pelliculosa* and *C. haemuloniii* caused clonal infection in NICU [11]. An outbreak of *C. tropicalis* fungemia in a NICU was traced to receipt of total parenteral nutrition and antimicrobial agents [23].

*Malassezia* species in immunocompromised patients may be associated with several skin conditions and systemic diseases, including folliculitis, seborrhoeic dermatitis, catheter-related fungemia and sepsis. However, this yeast may also cause invasive infections in critically ill low birth weight infants. *Malassezia* fungemia is predominantly caused by *Malassezia furfur* and *Malassezia pachydermatis*. *M. furfur* has been described predominantly in conjunction with nosocomial outbreaks in NICU, particularly in neonates and infants receiving intravenous lipids solution. Additionally, *M. pachydermatis* has been associated with bloodstream infection in preterm with very low birth weight and the prolonged use of indwelling catheters and parenteral lipid formulations [18, 24].
