**Fungal Infections in Neonatal Intensive Care**

**Fungal Infections in Neonatal Intensive Care**

DOI: 10.5772/intechopen.70302

Rejane P. Neves, Ana Maria R. de Carvalho Parahym, Carolina M. da Silva, Danielle P.C. Macêdo, André F.G. Leal, Henrique J. Neves and Reginaldo G. Lima-Neto Parahym, Carolina M. da Silva, Danielle P.C. Macêdo, André F.G. Leal, Henrique J. Neves and Reginaldo G. Lima-Neto Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

Rejane P. Neves, Ana Maria R. de Carvalho

http://dx.doi.org/10.5772/intechopen.70302

#### **Abstract**

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. Furthermore, immunologic immaturity and altered cutaneous barriers play some role in the vulnerability of neonates to nosocomial infections. In this context, the incidence of invasive fungal infections has increased significantly worldwide, representing an important infective complication in patients hospitalized in intensive care units. Invasive fungal infections in Neonatal Intensive Care Unit (NICUs) show high mortality; being species of *Candida,* the most isolates etiologic agents. The better prognosis of the patient is associated with the early diagnosis and fast treatment. However, guidelines to facilitate the optimal therapy choice for the treatment of neonatal fungal disease do not exist. The current antifungal agents that are available to treat fungemia among newborns and children are based on clinical trials in adults, since there are few comparative studies of antifungal agents in infants. The most commonly used drugs for the treatment of invasive fungal infections in neonates are classified in four different classes: polyene, azoles, analogs of pyrimidines and echinocandins.

**Keywords:** antifungal therapy, fungal infections, intensive care, neonates, sepsis

#### **1. Introduction**

During the last two decades, invasive fungal infections in preterm infants have become an increasing problem, mainly when hospitalized in a Neonatal Intensive Care Unit (NICU). Thus, for the last years, 6.3 million children under the age of 5 died each year are estimated,

Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons

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

context, *Candida* and *Malassezia* species are the most prevalent pathogen involved in fungal

Fungal Infections in Neonatal Intensive Care http://dx.doi.org/10.5772/intechopen.70302 111

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

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

*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

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

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

*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

because of *C. albicans*, whereas increased because of *C. parapsilosis* [20, 21].

total parenteral nutrition and antimicrobial agents [23].

parenteral lipid formulations [18, 24].

infections in NICU [18].

from 5 to 71% [16].

infants (<1000 g) [19].

a NICU [22].

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 [7–10].

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 characterizes greater pathogenicity and antifungal resistance of fungi.

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