Fungal Infections In Children Research Articles

Treatment of Invasive Fungal Infection in Childhood Acute Lymphoblastic Leukemia with Amphotericin B and Voriconazole

To study the clinical efficacy of amphotericin B and voriconazole in the treatment of invasive fungal infection in children with acute lymphoblastic leukemia(ALL) during chemotherapy. The clinical data of 214 patients with acute lymphoblastic leukemia admitted in our hospital from March 2014 to February 2017 was retrospectively analyzed. Among them 65 patients had invasive fungal infection (IFI) during the chemotherapy period, out of them 35 patients treated with voriconazole were enrolled in group A; anather 30 patients treated with amphotericin B were enrolled in group B. The clinical factors that affected the incidence of IFI was statistically analyzed. And the efficacy and adverse reactions in children with ALL were compared after treatment for 8 weeks. The incidence of IFI in children with ALL in this study was 30.37%, and was related with the duration of hospitalization and the level of neutrophil deficiency (P<0.05). The total effective rates of group A and group B were 72.28% and 43.33%, respectively, their difference was statistically significant between 2 group (P<0.05). The incidence of renal function impairment, digestive dysfunction and neurotoxicity were 8.57%, 5.71% and 5.71% in children with ALL treated with voriconazole respectively, which were lower than those in children treated with amphotericin B (P<0.05). The score index of Physical health, energy state, emotion control and overall health in group A were significantly higher than those in B group, and the difference was statistically significant (P<0.05). The occurrence of IFI in children with ALL relats with the time of hospitalization and the level of neutrophils. The clinical effect of voriconazole is better, and the incidence of adverse reactions can be reduced, suggesting important clinical significance.

Early bacterial and fungal infection in children receiving allogeneic stem cell transplantation for acute lymphoblastic leukemia in Argentina.

Infections are important complications associated with allogeneic HSCT. Describing infection rates in low- and middle-income countries provides data to infer efficacy of supportive care practices in these settings. In this retrospective cohort study, we included patients (age ≤ 18years) who underwent a first allogeneic HSCT for ALL in a single center in Argentina between 1998 and 2016. The primary outcome was sterile site bacterial infection. Secondary outcomes were proven or probable invasive fungal infection, TRM, and infectious deaths. There were 68 allogeneic HSCT recipients with ALL included in this analysis. Overall, 17 (25.0%) experienced at least one sterile site bacterial infection and 10 (14.7%) experienced at least one proven or probable invasive fungal infection. The TRM rate was 19.1%, and 3 (4.4%) patients died of infection. In a middle-income country center in Argentina, pediatric allogeneic HSCT infection rates, TRM, and infection-related mortality were comparable to high-income countries. These data support continuation of allogeneic HSCT programs in similar resource-limited settings provided that adequate supportive care and monitoring of outcomes can be performed.

Therapeutic drug monitoring of voriconazole for treatment and prophylaxis of invasive fungal infection in children.

Voriconazole therapeutic drug monitoring is not consistently recommended due to its high interpatient and intrapatient variability. Here, we aimed to describe our experience with voriconazole for treatment and prophylaxis of invasive fungal infections in paediatric patients. A fully validated high-performance liquid chromatography-mass spectrometry method was used to quantify voriconazole concentration in plasma, at the end of dosing interval. A high interindividual variability was shown. We enrolled 237 children, 83 receiving intravenous and 154 oral voriconazole. A positive correlation between drug dose and drug plasma exposure was observed. Considering intravenous route, patients with higher serum creatinine had higher voriconazole concentrations; a positive correlation was found among drug exposure and age. Sex significantly influenced drug levels: males had higher median drug concentrations than females (P<0.001). Close voriconazole pharmacokinetics monitoring should help individualize antifungal therapy for children.

Invasive Candida Infections (ICI) in Pediatric Population of a Tertiary Care Hospital in United Arab Emirates (UAE): Management and Time to Negative Culture

Background: Invasive candida infection is a growing problem in critically ill patients. Candida species are the most common agent responsible for invasive fungal infections in children. Timely diagnosis and proper selection of antifungal therapy are of paramount importance for a favorable outcome. The increasing rate of non-albiacans candida is becoming a real challenge when choosing an empirical antifungal therapy since a large percentage of them are resistant to azoles. This study aims at identifying the most commonly used antifungal agents in our institute and their success measured by the time needed to reach a negative culture (TNC) in cases of candidemia and candiduriaMethods:We performed a retrospective cohort study of all children (15 years and younger) with invasive candida infection, admitted to Tawam Hospital from 2008 to 2015.Results: Fluconazole seems to be the most common choice of our pediatricians in treating urine ICI (65%)while Amphotericin B Lipid complex is the most common choice in treating blood ICI(56%). Amphoteric B Lipid Complex was associated with the shortest TNC both in treating urine ICI (3 days) and blood ICI (4.4 days0Conclusions: Unfortunately, there aren’t many prospective studies in the literature comparing the efficacy of the major antifungal agents in treating pediatrics ICI. Therefore, we hope that this study, despite being retrospective, will shed some light on the utilization of Amphotericin B Lipid Complex in treating pediatrics ICI.

Epidemiological profile of tinea capitis in São Paulo City.

Tinea capitis is the most common fungal infection in children. The identification of the etiologic agent helps clinicians make their therapeutic choice. Studies conducted in different countries show a changing pattern of the main etiological agents according to their regions. We performed a retrospective study in the tertiary public service in São Paulo, analyzing the isolated etiological agents in patients with tinea capitis from March 2013 to May 2015. Microsporum canis was the main agent (56.6%), followed by Trichophyton tonsurans (36.6%). Despite recent migratory movements in the city, we observed no change in the causative agent of tinea capitis.

Advances in diagnosis and treatment of invasive pulmonary fungal infections in children

The prevalence of invasive pulmonary fungal infections (IPFIs) has increased in children, which becomes a clinical concern in recent years.With the availabilities of new diagnostic tools for fungi and more antifungal agents, children with IPFIs may achieve a much earlier diagnosis and treatment.This article reviewed the development of laboratory tests, diagnostic criteria, treatment strategies and commonly used antifungal agents for IPFIs. Key words: Invasive pulmonary fungal infections; Definitions with the classifications; Antifungal agents; Child

Gastrointestinal Basidiobolomycosis: An Emerging, and A Confusing, Disease in Children (A Multicenter Experience).

Gastrointestinal basidiobolomycosis (GIB) is an emerging fungal infection in children that leads to diagnostic confusion. Our study aim was twofold: a systematic review of published literature and an update of some Saudi Arabia hospital series to analyze their as well as our own experience in diagnosis and management of GIB. This clinical study included 18 children whose final diagnosis was GIB. The patients, who ranged in age from 5 to 10 years, were admitted between November 2009 and November 2015 with vague abdominal pains with or without abdominal masses for further investigation. Abdominal pain was the most common presenting symptom (94.4%) followed by constipation and abdominal mass (83.3 and 77.8%, respectively); fever was present in only 22.2% of the cases. Elevated inflammatory markers and eosinophilia (94.4%) appeared as prominent laboratory findings. We conclude that diagnosing GIB in children requires a high index of suspicion, awareness, and consideration of its possibility in the differential diagnosis in patients with abdominal masses and eosinophilia, particularly in areas where it is endemic. Increased awareness of this clinical entity, early surgical resection of the infected tissue, and prolonged treatment with itraconazole offer the best chance for curing the disease.

P247 Fungal infections in children with inflammatory bowel disease

P247 Fungal infections in children with inflammatory bowel disease

Fungal Skin Infections.

1. Aditya K. Gupta, MD, PhD, FRCP(C), FAAD*,† 2. Melissa A. MacLeod, MSc† 3. Kelly A. Foley, PhD† 4. Gita Gupta, MD‡ 5. Sheila Fallon Friedlander, MD§ 1. *Division of Dermatology, Department of Medicine, University of Toronto, Toronto, Ontario, Canada 2. †Mediprobe Research, Inc, London, Ontario, Canada 3. ‡Wayne State University, Detroit, MI 4. §Dermatology and Pediatrics, Pediatric Dermatology Training Program, University of California at San Diego School of Medicine, Rady Children’s Hospital, San Diego, CA * CMC: : Chronic mucocutaneous candidiasis HIV: : Human immunodeficiency virus id: : Dermatophytid KOH: : Potassium hydroxide MC: : Mucocutaneous candidiasis PCR: : Polymerase chain reaction PV: : Pityriasis versicolor TP: : Tinea pedis Most pediatricians appear to be familiar with candidal diaper dermatitis, but there is a lack of knowledge about other, less common fungal infections in children. After completing this article, readers should be able to: 1. Recognize the clinical presentations of different fungal infections in children. 2. Know the differential diagnosis of various fungal skin infections. 3. Know what diagnostic tests can be used to confirm infection. 4. Be aware of available treatment options and how to manage the infections appropriately. Candidal diaper dermatitis is the most common fungal infection of childhood. This yeast infection almost always secondarily invades diaper-area skin that has been damaged by an irritant contact dermatitis from maceration, urine, and/or stool. Children in the preschool-age group who no longer wear diapers are more likely to develop tinea infections, particularly tinea capitis. Tinea refers to dermatophyte infections in the epidermis and areas high in keratin, such as the hair and nails. In prepubertal children, tinea capitis and tinea corporis are most common; in adolescence, tinea pedis (TP), tinea cruris, and tinea unguium (onychomycosis) are more common. (1) Yeast infections other than candidal diaper dermatitis, including pityriasis versicolor (PV) (formerly known as tinea versicolor) and mucocutaneous candidiasis …

Voriconazole plus caspofungin for treatment of invasive fungal infection in children with acute leukemia.

BackgroundInvasive fungal infections (IFIs) are a life-threatening problem in immunocompromised patients. Despite timely diagnosis and appropriate antifungal therapy, clinical outcomes of IFIs remain unsatisfactory, necessitating treatment with a combination of antifungal agents. Therefore, childhood leukemic patients treated with voriconazole plus caspofungin were evaluated for the safety and efficacy of the combination antifungal therapy to treat IFIs.MethodsIn this retrospective study, medical records were retrieved for patients admitted to the Pediatric Department of Yeungnam University Hospital, Daegu, South Korea, between April 2009 and May 2013. Medical records of 22 patients were analyzed.ResultsOf the 22 patients studied, nine (41%) had been diagnosed with probable IFI, and 13 (59%) with possible IFI. All patients, except one, were already receiving antifungal monotherapy for the treatment of neutropenic fever. After a diagnosis of IFI was confirmed, antifungal monotherapy was replaced with combination therapy. The study's overall response rate was 90.9%, with complete responses in 86.3% of the patients. Two patients experienced a side effect of a small increase in liver enzyme levels.ConclusionVoriconazole plus caspofungin combination therapy is an effective and safe treatment for serious IFI in pediatric patients with acute leukemia.

Treating Common Fungal Infections in Children

Purpose of Review The purpose of this paper is to provide a framework for the paediatric practitioner to approach common superficial fungal infections and less frequent but difficult to manage allergic mycoses and invasive fungal infections. Important research findings are summarised and diagnostic and therapeutic guidance is provided. Best practice recommendations to guide the use of topical and systemic antifungals to treat superficial and invasive paediatric fungal infections are outlined here.

Efficacy and safety of caspofungin in children: systematic review and meta-analysis.

Invasive fungal infections are a significant cause of morbidity and mortality in children. Caspofungin is an echinocandin used as an alternative treatment in the prevention and/or treatment of certain invasive fungal infections in children, although compared to the standard treatment there is little evidence on its efficacy and safety. To evaluate the efficacy and safety of caspofungin compared with other antifungal drugs for the prevention and/or treatment of invasive fungal infections in children. The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. The objective of the initial search strategy was to identify randomized controlled studies of acceptable methodological quality (Jadad scale >3), through the key word "caspofungin", conducted in patients with an age range from 0 to 18 years old. This systematic review suggests that caspofungin could be considered as an alternative drug in children for the prevention and treatment of invasive fungal infections. However, given the small number of existing publications, more studies are required to reach definite conclusions.

Detection of β-D-glucan for the diagnosis of invasive fungal infection in children with hematological malignancy

The ß-D-glucan assay (BDG) has been added to the EORTC/MSG criteria for the diagnosis of invasive fungal infections (IFI), but data from pediatric populations is scarce. The aim of this study was to evaluate performance of BDG in a cohort of hemato-oncological children with hematological malignancy at risk for IFI. 113 patients were included through an 18-month period. In addition to routine IFI screening, BDG was assayed once a week. IFIs were classified using EORTC/MSG criteria without including the BDG results. Performances were assessed after a ROC analysis for optimization and multivariate analysis to detect the causes of false positivity. 8 proven and 4 probable IFIs, and 7 possible IFIs were diagnosed in 9 and 7 patients, respectively. Sensitivity and specificity increased from 75% and 56% to 100% and 91.1%, respectively when considering the whole population and patients not having received any antifungals prior to the test. Multivariate analysis revealed that being younger than 7, severe colitis/mucositis, recent administration of polyvalent immunoglobulins and digestive colonization with Enterococcus sp were independent risk factors for false positivity. BDG is a valuable test to detect IFI in pediatric patients not previously treated with antifungals and to detect the occurrence of chronic infection.

Superficial Fungal Infections in Children

Objective : The study was performed to determine the prevalence and the demographic characteristics of patients, who were diagnosed with superficial fungal infection at the dermatology department of two centers, and compare their epidemiologic data to those reported in the literature. Material and Method : Files of 20716 children, between 0 and 16 years of age, who presented to the Dermatology Outpatient Clinic between 2011 and 2015, were investigated retrospectively. Of these, 518 children, diagnosed with superficial fungal infection, were evaluated with respect to age, gender, presence of systemic disease and demographics. The diagnosis and the laboratory investigations performed were recorded Results : There were 251 girls (48%) and 267 boys (52%), diagnosed with superficial fungal infection. 8 types of superficial fungal infection were detected in 518 patients (2.5%). Assessment by age group revealed the following: 8.4% of the infection were observed between 0 and 2 years of age (n=44), 16.9% were observed (n=88) between 3 and 5 years of age, 34.9% were observed (n=181) between 6 and 11 years of age and 39.5% were observed between 11 and 16 years of age (n=205). Tinea corporis(26%, n=136) and pityriasis versicolor (19%, n=99), candidiasis (17%, n=86) and tinea pedis (14%, n=72) were the most commonly detected ones. Conclusion: While superficial fungal infections occur less in children compared to adults, early diagnosis and treatment is important due to potentially permanent complications. In addition, with respect to preventive medicine, being aware of the factors that would reduce transmission would prevent occurrence of complications.

Prophylactic administration of voriconazole with two different doses for invasive fungal infection in children and adolescents with acute myeloid leukemia.

Pediatric patients under treatment for acute myeloid leukemia (AML) are at high risk for invasive fungal infection (IFI). We evaluated the efficacy of prophylactic administration of voriconazole (VRCZ) with two different doses. Between October 2005 and June 2011, 17 children and adolescents (aged 0-20 years) undergoing chemotherapy for AML were prophylactically administered with 5mg/kg/d of oral VRCZ. Furthermore, 22 AML patients (aged 0-19 years) were administered 10mg/kg/d of oral VRCZ between July 2011 and December 2014. The incidences of IFI with two different doses of VRCZ were compared. Irrespective of the dosage of VRCZ, eight patients developed IFI. Of these eight patients, four belonged to the 5mg/kg/d group and four to the 10mg/kg/d group. Cumulative incidences of IFI at 180 days after the initiation of chemotherapy were not different between the 5mg/kg/d and 10mg/kg/d groups. The trough plasma VRCZ concentration in the 10mg/kg/d group ranged from < 0.09μg/mL to 2.17μg/mL, with a median level of 0.27μg/mL, and patients with the targeted trough concentration (1-4μg/mL) comprised only 18.8% of the evaluable patients in this group, whereas the trough plasma VRCZ concentration of the evaluable patients in the 5mg/kg/d group were all below the limit of sensitivity (< 0.09μg/mL). More dose escalation is required based on this study. As VRCZ concentration is considerably influenced by genetic polymorphisms and drug-drug interactions, VRCZ should be used under therapeutic drug monitoring to keep effective drug concentrations.

Fungal infections in children in the early postoperative period after cardiac surgery for congenital heart disease: a single-centre experience.

Postoperative infections are still an important problem in cardiac surgery, especially in the paediatric population, and may influence the final outcome of congenital heart disease treatment. Postoperative infections with fungi are uncommon. The aetiology is poorly understood, and the proper diagnosis and treatment is unclear. In this single-centre study, the frequency of invasive fungal disease in children who underwent surgical management of congenital heart diseases was determined along with the risk factors for infection, treatment options and outcomes. All consecutive paediatric patients (<18 years of age) who underwent cardiac surgery for congenital heart disease between September 2008 and December 2015 in a paediatric cardiac centre in Poland were identified. Those who developed invasive fungal disease in the early postoperative period (30 days) were identified. Of the 1540 cardiosurgical procedures for congenital heart disease, 6 were complicated by fungal infection (0.39%). One patient had a high probability of fungal infection, but the diagnosis was unproved. Nevertheless, the patient was successfully treated with antifungal treatment. Five had proven invasive fungal disease. Of these, 3 were diagnosed with candidaemia. All had undergone cardiopulmonary bypass. Of the remaining 2 patients, 1 was a preterm newborn with complete atrioventricular septal defect who developed rib fungal invasion. The remaining patient had pulmonary atresia with ventricular septal defect and developed Fournier's gangrene after surgery. None of the patients died due to infection in the early postoperative period. However, the child with rib fungal invasion died 39 days after surgery as a result of multiorgan failure. Fungal infections in paediatric patients after cardiac surgery may markedly influence morbidity and mortality. Fungal infection prophylaxis in this specific group of children may reduce morbidity, whereas early empirical treatment followed by a targeted approach may improve outcomes. The 'hit fast, hit hard' treatment strategy may be the best rescue option for children who develop invasive fungal disease after cardiac surgery.

Use of Fungal Diagnostics and Therapy in Pediatric Cancer Patients in Resource-Limited Settings.

Fungal diseases are an important cause of mortality in immunocompromised hosts, and their incidence in pediatric cancer patients in low- to middle-income countries is underestimated. In this review, we present relevant, up-to-date information about the most common opportunistic and endemic fungal diseases among children with cancer, their geographic distribution, and recommended diagnostics and treatment. Efforts to improve the care of children with cancer and fungal disease must address the urgent need for sustainable and cost-effective solutions that improve training, fungal disease testing capability, and the use of available resources. We hope that the collective information presented here will be used to advise healthcare providers, regional and country health leaders, and policymakers of the current challenges in diagnosing and treating fungal infections in children with cancer in low- to middle-income countries.

Factors in Etiology and Predisposition of Adult Tinea Capitis and Review of Published Literature.

Tinea capitis is a common fungal infection in children but is less frequently encountered in adults, especially in immunocompromised individuals. To determine the incidence of tinea capitis in adults, the predisposing factors and causative species. A retrospective study was conducted over a period of 5years, from 2010 to 2015, on cases of tinea capitis diagnosed in the Department of Dermatology and Mycology Research Center in Tehran, Iran. The information was collected from the patients including age, gender, location of the lesions, results of direct examination and culture, cause of immunosuppression and the prescribed treatment. Twenty-five (20.6%) patients (10 men and 15 women) with a mean age of 45.28years were affected by tinea capitis among a total number of 121 positive cases. Most of these adults (80%) had a grade of immunodeficiency due to the underlying syndromes or diseases, and the rest were immunocompetent. Trichophyton species were isolated from 84% of these adult patients, indicating Trichophyton violaceum (T. violaceum) as the most common fungal agent. Treatment with oral terbinafine or itraconazole was successful in all these cases. The results showed that most cases affecting the adult population were caused by species of the genus Trichophyton. T. violaceum was the most common dermatophyte of adult patients. Thus, it is important to consider tinea capitis as a differential diagnosis in immunocompromised adults, even though it is considered to be rare in adults.

The European Paediatric Mycology Network (EPMyN): Towards a Better Understanding and Management of Fungal Infections in Children

The European Paediatric Mycology Network (EPMyN) was launched in 2014 to create a European platform for research and education in the field of paediatric mycology. The EPMyN aims to address the lack of paediatric specific evidence and knowledge needed to (1) improve the management and outcome of invasive fungal infections in children and neonates and to (2) enhance and develop paediatric antifungal stewardship programmes.

Voriconazole plasma levels, its determinants, and impact on outcome of invasive fungal infections in children with cancer: a prospective study

Voriconazole plasma levels, its determinants, and impact on outcome of invasive fungal infections in children with cancer: a prospective study