Invasive fungal infections (IFIs) appear to have increased in recent years and are associated with significant morbidity and mortality in children. The incidence of IFIs has significantly increased in pediatric cancer patients, in preterm neonates, patients with primary immune deficiencies and non-neutropenic children requiring intensive care unit stay Citation[1]. Studies describing the epidemiology, clinical and laboratory characteristics, and therapeutic interventions of IFI have been mostly performed in adult populations. There are important differences regarding epidemiology, diagnosis and treatment of IFIs between children and adults Citation[2]. This issue of Expert Review of Anti-infective Therapy focuses on IFI during childhood and includes reviews discussing the epidemiology and clinical findings of common IFIs in children: the important differences with respect to adults and diagnostic laboratory techniques, and summarizes the recent advances in currently available and future therapeutic options.
Early mycological diagnosis and prompt implementation of antifungal therapy are crucial for surviving IFI in patients of all ages. Unfortunately, early identification of the etiologic pathogen causing an IFI is extremely difficult in neonates and children. Lehrnbecher and Groll summarize the current perpectives about IFI in newborns and children in this issue Citation[2]. There is often difficulty in collecting appropriate tissue specimens for culture or histology, fungal cultures lack sensitivity, histological diagnosis requires invasive procedures, imaging studies lack specificity, galactomannan antigen detection has a relatively low sensitivity in children compared with adults, and fungal DNA detection has not been fully validated. In this issue, Oz and Kiraz summarize current laboratory examinations for IFI from a pediatric perspective Citation[3].
This issue of Expert Review of Anti-infective Therapy is focused on Candida and Aspergillus spp. because they are the most commonly isolated organisms in pediatric IFIs. There has been a steady rise in cases of, and fatality due to pediatric invasive candidiasis and aspergillosis in children. Candidiasis is a concern in children with hematological malignancies, bone marrow and solid organ transplant recipients as well as non-neutropenic children in different hospital settings including the intensive care unit, as discussed by Lehrnbecher and Groll, and Zaoutis Citation[2,4]. With regard to aspergillosis, in addition to children with hematological malignancy and solid organ transplantation, children with primary immune deficiencies including chronic granulomatous disease and cystic fibrosis are at high risk of invasive aspergillosis Citation[5]. In this special issue, Candida infections and Aspergillus infections are extensively discussed in different pediatric populations including non-neutropenic children, hematological malignancies, bone marrow and solid organ transplantation. Şensoy and Belet review Candida infections in solid organ recipient children in this issue Citation[6]. Özen and Dündar evaluate Aspergillus infections in children with hematological malignancies Citation[7] and Salman et al. review invasive aspergillosis in bone marrow and solid organ transplant recipients Citation[8]. Although less common than candidiasis and aspergillosis, zygomycosis has been increasing and carries a high mortality rate in children Citation[2].
Early recognition and rapid initiation of effective treatment is a prerequisite for successful management of children with IFI. This special issue includes separately and extensively all antifungal agents in use including classic agents, newcomers and those under investigation. Dedicated guidelines outlining the choices for optimal therapy in the treatment of neonatal or pediatric fungal disease do not exist. Antifungal agents are reviewed according to pharmacokinetic and pharmacodymanic data, and results of the randomized clinical trials, case series, case reports, adverse effects and antifungal toxicities are discussed. Similarly, when initiating antifungal therapy, physicians should be aware about specific pharmacokinetic properties of antifungal agents for the treatment of children. Currently, there are four classes of drug for treatment of IFI: polyenes, triazoles, echinocandins and nucleoside analogues. Amphotericin B formulations and caspofungin use in children were extensively presented in this special focus issue by Kuyucu and Somer et al.Citation[9,10]. Given the difficulties in performing adequately powered efficacy trials in children, the ongoing extrapolation of adult data to pediatric practice is likely to be required. Results of adult studies are presented when pediatric studies are insufficient.
In this special focus issue, newer antifungal agents have been discussed. Andiulafungin and second-generation triazoles, such as isavuconazole, ravuconazole and albaconazole, show promise in the treatment of IFI, however, there are no recommendations regarding the use of these agents in children. These issues are discussed by Tap?s?z and Türel Citation[11,12]. Additional research studies are needed to define the exact dosage for newer antifungal agents in children. Further comparative pediatric antifungal drug trials and epidemiological and pharmacological studies are required, highlighting the differences between neonates, children and adults with IFIs. These issues are highlighted by Steinbach and Maschmeyer Citation[13,14].
Pediatricians and subspecialists need to remain aware of optimal diagnostic and therapeutic options because IFIs continue to be associated with significant mortality and morbidity. With this issue of Expert Review of Anti-infective Therapy we hope to increase the knowledge about IFIs in newborns and children and to define standard/better approaches for this important disease in children.
Financial & competing interests disclosure
The author has no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.
No writing assistance was utilized in the production of this manuscript.
References
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