Candidemia in children: Epidemiology, prevention and management.

Candidemia is the leading cause of invasive fungal infections in hospitalised children. The highest rates of candidemia have been recorded in neonates and infants <1 year of age. Candidemia is more frequent in neonates and young infants than in adults, and is associated with better clinical outcomes, but higher inpatient costs. Over the last 10 years, a declining trend has been noted in the incidence of paediatric candidemia in the US and elsewhere due to the hospital-wide implementation of central-line insertion and maintenance bundles that emphasise full sterile barrier precautions, chlorhexidine skin preparation during line insertion, meticulous site and tubing care, and daily discussion of catheter necessity. Additional interventions aiming at reducing gut-associated candidemia are required in immunocompromised and critically ill children.

Chromoblastomycosis.

Chromoblastomycosis (CBM), also known as chromomycosis, is one of the most prevalent implantation fungal infections, being the most common of the gamut of mycoses caused by melanized or brown-pigmented fungi. CBM is mainly a tropical or subtropical disease that may affect individuals with certain risk factors around the world. The following characteristics are associated with this disease: (i) traumatic inoculation by implantation from an environmental source, leading to an initial cutaneous lesion at the inoculation site; (ii) chronic and progressive cutaneous and subcutaneous tissular involvement associated with fibrotic and granulomatous reactions associated with microabscesses and often with tissue proliferation; (iii) a nonprotective T helper type 2 (Th2) immune response with ineffective humoral involvement; and (iv) the presence of muriform (sclerotic) cells embedded in the affected tissue. CBM lesions are clinically polymorphic and are commonly misdiagnosed as various other infectious and noninfectious diseases. In its more severe clinical forms, CBM may cause an incapacity for labor due to fibrotic sequelae and also due to a series of clinical complications, and if not recognized at an early stage, this disease can be refractory to antifungal therapy.

Platelet Mass Predicts Intracranial Hemorrhage in Neonates With Gram-negative Sepsis.

Neonatal sepsis due to gram-negative bacteria is associated with severe hemorrhagic conditions, such as intracranial hemorrhage (ICH). The aim of the study was to investigate the significance of platelet (PLT) count and platelet mass (PM) in predicting promptly neonatal ICH. Demographics, species, PLT, PM, ICH, and outcome for neonates with gram-negative sepsis for the period 2005 to 2012 were retrospectively recorded. Eighty-four infants were enrolled with median gestational age 30 weeks, median birthweight 1481.5 g, and median age at sepsis diagnosis 23 days. The most frequently isolated bacteria were Enterobacter spp. (38.1%). ICH occurred in 16 neonates (19%), whereas the mortality rate was 25% (21 neonates). The median PLT count and PM at days 1, 2, and 3 after diagnosis of gram-negative sepsis was significantly associated with the presence of ICH. Regression analysis revealed the cutoff predictive value of 355 fL/nL for the PM at day 3 (area under the curve: 75, sensitivity 90%, P=0.002). PM levels could play an important role in predicting the occurrence of ICH in high-risk neonates.

Fungal Endocarditis in Neonates: A Review of Seventy-one Cases (1971-2013).

BACKGROUND: Fungal endocarditis (FE) remains an uncommon but life-threatening complication of invasive fungal infections. As data on neonatal FE are scant, we aimed to review all published experience regarding this serious infection. METHODS: Neonatal FE cases published in PubMed (1971-2013) as single cases, or case series were identified using the terms "fungal endocarditis, neonates and cardiac vegetation." Data on predefined criteria including demographics, predisposing factors, mycology, sites of cardiac involvement, therapy and outcome were collected and analyzed. RESULTS: The dataset comprised 71 neonates with FE. Median birth weight was 940 g [interquartile range (IQR): 609], median gestational age 27 weeks (IQR: 6) and median postnatal age at diagnosis 20 days (IQR: 20). Ninety-two percent of the patients were premature. Right atrium was the most common vegetation site (63%). Seventy-one percent of the cases reported were associated with previous central venous catheters. Candida albicans was the most predominant fungal species (59%). Amphotericin B monotherapy was used in 42.2% and fluconazole in 2.8%. Amphotericin B with flucytosine (25.3%) was the most frequent combined regimen. Surgical treatment was conducted in 28%. Overall mortality was 42.2%. Initiation with combined antifungal treatment was associated with lower mortality than monotherapy (24.2% vs. 51.7%, respectively, P = 0.036). CONCLUSIONS: Neonatal FE most frequently occurs in very premature infants and is associated with central venous catheters. C. albicans is the predominant fungus. Although outcome has been dismal, it may be improved with combined antifungal therapy.

Mannose binding lectin and ficolin-2 polymorphisms are associated with increased risk for bacterial infections in children with B acute lymphoblastic leukemia.

BACKGROUND: We aimed to investigate whether the presence of mannose binding lectin (MBL2), ficolin 2 (FCN2) polymorphisms or the combined deficiency significantly influence the risk and subsequently the frequency of chemotherapy-induced bacterial infections in children with B acute lymphoblastic leukemia (B-ALL). PROCEDURE: MBL2 polymorphisms for exon 1 and FCN2 polymorphisms for promoter regions -986, -602, -557, -64, -4 and exon 8 regions +6,359, +6,424 were determined in children with B-ALL. FCN2 haplotype was determined by gene sequencing. Number and duration of FN episodes as well as number of bacterial infections were recorded during induction chemotherapy. RESULTS: Forty-four children with B-ALL (median age 4.3 years, 65.9% males) suffered from 142 FN episodes and 92 bacterial infections (40.2% Gram positive and 59.8% Gram negative). MBL2 low-risk genotype was found in 59.1%, medium-risk in 31.8% and high-risk in 9%. FCN2 low-risk haplotypes were detected in 38.2%, medium-risk in 44.1% and high-risk in 17.6%. MBL2 genotype and FCN2 haplotype were not associated with increased frequency of FN episodes. MBL2 medium/high-risk genotype and FCN2 medium/high-risk haplotype were associated with prolonged duration of FN (P = 0.007 and P = 0.001, respectively) and increased number of bacterial infections (P = 0.001 and P = 0.002, respectively). The combined MBL2/FCN2 medium/high-risk genotype was associated with an increased number of bacterial infections (P = 0.001). CONCLUSIONS: MBL2 and FCN2 single or combined deficiencies are associated with increased duration of FN episodes as well as increased number of bacterial infections in children with B-ALL suggesting a prognostic role of these genes.

Endothelial activation and inflammation biomarkers in children and adolescents with sickle cell disease.

Sickle cell disease pathogenesis is a complex interplay of multiple factors associated with vascular endothelial activation, intense oxidative stress, and increased sickle cell adhesion. The aim of this study was to determine and compare three panels of plasma circulating biomarkers at 'steady state' and during veno-occlusive crises (VOC) in a cohort of children and adolescents with SCD and healthy controls. The following biomarkers were assessed: acute phase reactants, endothelial factors, and adhesion molecules. Forty-one SCD pediatric patients and 28 healthy children were enrolled. Patients at 'steady state' presented significantly elevated plasma levels of endothelin-1 (ET-1), soluble-VCAM-1 (sVCAM-1), soluble P-selectin (sP-selectin), and d-dimers compared to the control group. ET-1, sP-selectin, platelet-derived growth factor (PDGF), von Willebrand factor (vWf), d-dimers, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) seems to represent additional, but not independent, prognostic markers of VOC crisis. Elevated plasma levels of sP-selectin, ET-1, and sVCAM-1 were associated with VOC frequency. The present study provides preliminary evidence of a possible association between these biomarkers and the endothelial activation at steady state and VOC in childhood SCD. Further prospective studies are required to confirm the potential independent prognostic value of these markers in different stages of pediatric SCD.

Non-Aspergillus fungal infections in chronic granulomatous disease.

Chronic granulomatous disease (CGD) is a congenital immunodeficiency, characterised by significant infections due to an inability of phagocyte to kill catalase-positive organisms including certain fungi such as Aspergillus spp. Nevertheless, other more rare fungi can cause significant diseases. This report is a systematic review of all published cases of non-Aspergillus fungal infections in CGD patients. Analysis of 68 cases of non-Aspergillus fungal infections in 65 CGD patients (10 females) published in the English literature. The median age of CGD patients was 15.2 years (range 0.1-69), 60% of whom had the X-linked recessive defect. The most prevalent non-Aspergillus fungal infections were associated with Rhizopus spp. and Trichosporon spp. found in nine cases each (13.2%). The most commonly affected organs were the lungs in 69.9%. In 63.2% of cases first line antifungal treatment was monotherapy, with amphotericin B formulations being the most frequently used antifungal agents in 45.6% of cases. The overall mortality rate was 26.2%. Clinicians should take into account the occurrence of non-Aspergillus infections in this patient group, as well as the possibility of a changing epidemiology in fungal pathogens. Better awareness and knowledge of these pathogens can optimise antifungal treatment and improve outcome in CGD patients.

Transient myeloproliferative disorder in a newborn with down syndrome treated with rasburicase for the risk of development of tumor lysis syndrome: A case report.

INTRODUCTION: Transient myeloproliferative disorder is a hematologic abnormality characterized by an uncontrolled proliferation of myeloblasts in peripheral blood and bone marrow that primarily affects newborns and babies with Down syndrome. Tumor lysis syndrome is rarely associated with transient myeloproliferative disorder. CASE PRESENTATION: Transient myeloproliferative disorder was diagnosed in a seven-day-old baby girl with Down syndrome, who was referred to our department due to hyperleukocytosis. Our patient developed tumor lysis syndrome, successfully treated with rasburicase, as a complication of transient myeloproliferative disorder resulting from rapid degradation of myeloid blasts after initiation of effective chemotherapy. CONCLUSIONS: Tumor lysis syndrome is rarely reported as a complication of transient myeloproliferative disorder. To the best of our knowledge, this is the first case of a newborn with Down syndrome and transient myeloproliferative disorder treated with rasburicase for developing tumor lysis syndrome.

Risk of azole-enhanced vincristine neurotoxicity in pediatric patients with hematological malignancies: old problem - new dilemma.

One of the most well-known drug interactions in pediatric oncology concerns the co-administration of itraconazole, an antifungal triazole, and vincristine, an antileukemic agent, which seems to enhance the risk of neurotoxicity of the latter, mediated through the cytochrome CYP450 enzyme system. The aim of this article is to review the metabolism of these two drugs, to analyze the published cases with severe triazole-enhanced vincristine neurotoxicity, to discuss the pathophysiological mechanisms of this adverse effect, and to contribute in understanding the differences in triazole-vincristine interaction severity.