posaconazol in children's

PURPOSE: To establish the population pharmacokinetics (PPK) model of cyclosporine A(CsA) in pediatric patients with thalassemia undergoing allogeneic hematopoietic stem cell transplantation (HSCT), aiming at providing a reference for clinical dose individualization of CsA. METHODS: Children with thalassemia who underwent allogeneic HSCT were enrolled retrospectively. The PPK structural model and the random variable model of CsA were established on NONMEN. And goodness of fit plots (GOFs), visual predictive check (VPC), and bootstrap and normalized prediction distribution errors (NPDE) were used to evaluate the final model...

Erratic absorption of posaconazole oral suspension necessitates frequent dosing and administration with meals or supplements. Alternative enteral formulations are desirable for patients intolerant to enteral nutrition. Crushed posaconazole delayed-release tablets (POS-DRT) show promise in adults; limited evidence exists in children. We used crushed POS-DRT in 10 encounters with nine pediatric patients, achieving target POS concentrations in 90% of encounters. This highlights crushed POS-DRT as a potential enteral option for pediatric antifungal prophylaxis and treatment...

Invasive fungal diseases (IFDs) play an important role in the supportive care of paediatric patients with acute leukaemia and those undergoing allogeneic haematopoietic cell transplantation, and they are associated with significantly decreased overall survival rates in affected individuals. Relative to adults, children and adolescents are distinct in terms of host biology, predisposing conditions, presentation and epidemiology of fungal diseases, and in the pharmacology of antifungal agents. The paediatric development of antifungal agents has moved forward in a coordinated manner, and major advances have been made regarding concepts and recommendations for the prevention and treatment of IFDs...

Leukemia complicated with Mucor and Aspergillus coinfection is very rare, which is difficult to diagnose, and life-threatening. The clinical characteristics, diagnosis and treatment in a child with acute myeloid leukemia (AML), who developed mucormycosis and aspergillus coinfection after chemotherapy, was reported. This case was a 12-year-old boy who presented with fever and cough during chemotherapy. Rhizomucor pusillus and Aspergillus flavus were detected in his blood, cerebrospinal fluid and alveolar lavage fluid by metagenomic next-generation sequencing (mNGS)...

We aimed to assess patient exposure to isavuconazole from samples received in our laboratory for therapeutic antifungal monitoring. We used liquid chromatography coupled with ultraviolet absorbance detection adapted from a multiplex validated method with photodiode array detection to monitor the analytes. The latter device allows the characterization of the azoles UV spectra. The method was validated according to international guidelines for efficient isavuconazole monitoring. The assay exhibited linearity between 0...

Mucormycosis is a very rare fungal infection in children. It is caused by opportunistic fungi and mainly affects immunocompromised patients. Early diagnosis is very important for a good outcome. Successful management requires the reversal of the underlying predisposing risk factors, surgical debridement and prompt administration of active antifungal agents, with liposomal amphotericin B being the first-line therapy. This case, to the best of the authors' knowledge, is the first rhino-orbital-cerebral mucormycosis to be reported on among Omani children...

Invasive fungal infections are a major cause of morbidity and mortality for immunocompromised patients. Posaconazole is approved for treatment and prophylaxis of invasive fungal infection in adult patients, with intravenous, oral suspension, and gastroresistant/delayed-released tablet formulations available. In Europe, until very recently, posaconazole was used off-label in children, although a new delayed-release suspension approved for pediatric use is expected to become available soon. A population pharmacokinetic model was developed which uses posaconazole therapeutic drug monitoring data following intravenous and oral dosing in hospitalized children, thus enabling estimation of pediatric suspension and tablet oral bioavailability...

BACKGROUND AND OBJECTIVE: Posaconazole (PSZ) is a triazole antifungal for the management of invasive fungal disease (IFD) in adults and children. Although PSZ is available as an intravenous (IV) solution, oral suspension (OS) and delayed-release tablets (DRTs), OS is the preferred formulation for pediatric use because of potential safety concerns associated with an excipient in the IV formulation and difficulty in swallowing intact tablets by children. However, poor biopharmaceutical characteristics of the OS formulation leads to an unpredictable dose-exposure profile of PSZ in children, potentially risking therapeutic failure...

Invasive pulmonary aspergillosis (IPA) is a severe condition in immunocompromised children, but the optimal management is still under debate. In order to better clarify this issue, a literature search was performed through MEDLINE/PubMed database to describe current risk factors and diagnostic, therapeutic and prophylactic tools for invasive pulmonary aspergillosis (IPA) in the paediatric age. Observational studies and clinical trials regarding diagnosis, treatment and prophylaxis were considered, and results were summarised...

BACKGROUND: Liver transplantation is increasing worldwide with underlying pathologies dominated by metabolic and alcoholic diseases in developed countries. METHODS: We provide a narrative review of invasive aspergillosis (IA) in liver transplant (LT) recipients. We searched PubMed and Google Scholar for references without language and time restrictions. RESULTS: The incidence of IA in LT recipients is low (1.8%), while mortality is high (∼50%)...

BACKGROUND: Glucocorticoids are crucial components of the treatment of leukemia and lymphoma. High doses can lead to suppression of the hypothalamic-pituitary-adrenal (HPA) axis and be causative for an impaired stress response during infection. This study aims to evaluate the cortisol response in pediatric oncologic patients during febrile episodes. METHODS: Totally, 75 children and adolescents (5 months-18 years) with fever during chemotherapy were consecutively enrolled in this study...

We described a 14-year-old girl with acute lymphoblastic leukemia who developed disseminated mucormycosis during induction therapy. Disseminated Cunninghamella elegans infection was confirmed by histopathology, microbiological culture, and metagenomic next-generation sequencing analysis of skin tissue, blood, and cerebrospinal fluid. Subsequently, the patient received a combination of liposomal amphotericin B, posaconazole, and caspofungin for antifungal treatment, but eventually died because of severe fungal pneumonia, respiratory failure, and septic shock...

Posaconazole is often used for the prophylaxis and treatment of invasive fungal infections (IFI). However, intra- and inter-individual differences and drug interactions affect the efficacy and safety of posaconazole. Precision dosing of posaconazole based on the population pharmacokinetic (PopPK) model may assist in making significant clinical decisions. This review aimed to comprehensively summarize the published PopPK models of posaconazole and analyze covariates that significantly influence posaconazole exposure...

Sirolimus is used to treat pediatric patients with PIK3CD mutation-related immunodeficiency disease. However, the initial dosages of sirolimus remain undecided. The present study aims to explore initial dosages in pediatric patients with PIK3CD mutation-related immunodeficiency disease. Pediatric patients with this disease were analyzed using the population pharmacokinetic (PPK) model and the Monte Carlo simulation. Body weight and concomitant use of posaconazole were included in the final PPK model, where, under the same weight, clearances of sirolimus were 1 : 0...

Magnusiomyces capitatus (also denominated " Geotrichum capitatum " and "the teleomorph stage of Saprochaete capitata ") mainly affects immunocompromised patients with hematological malignancies in rare cases of invasive fungal infections (IFIs). Few cases have been reported for pediatric patients with acute lymphoblastic leukemia (ALL), in part because conventional diagnostic methods do not consistently detect M. capitatus in infections. The current contribution describes a systemic infection in a 15-year-old female diagnosed with ALL...

Invasive aspergillosis (IA) is associated with significant morbidity and mortality. Voriconazole remains the drug of choice for the treatment of IA in children; however, the complex kinetics of voriconazole in children make dosing challenging and therapeutic drug monitoring (TDM) essential for treatment success. The overarching goal of this review is to discuss the role of voriconazole, posaconazole, isavuconazole, liposomal amphotericin B, echinocandins, and combination antifungal therapy for the treatment of IA in children...

We report a case of mucormycosis induced by Cunninghamella spp. infection in a ten-year-old girl with acute lymphoblastic leukemia, who developed fever and respiratory symptoms after chemotherapy and was diagnosed with invasive fungal disease. Peripheral blood DNA sequences were analyzed using metagenomic next-generation sequencing (mNGS), and by comparison with the Pathogens Metagenomics Database (PMDB), we identified Cunninghamella spp. with sequence number 514 as the pathogen. The patient was treated with amphotericin B combined with posaconazole and showed a favorable response...

Experience in the clinical use of posaconazole (PCZ) in pediatric patients is limited, and no specific dose recommendations exist. This study aimed to investigate an appropriate dosing regimen, and assess the exposure-response relationships of PCZ in children. We reviewed the medical records of inpatients aged <18 years who subjected to PCZ concentrations monitoring. Clinical data, PCZ dosing and monitoring data were collected. A total of 375 PCZ trough concentrations ( C min ) from 105 pediatric patients were included...

The present study explored the effects of posaconazole on tacrolimus population pharmacokinetics (PPK) in children with Crohn's disease (CD) undergoing hematopoietic stem cell transplantation (HSCT). Tacrolimus concentrations, physiological and biochemical factors, and concomitant medications from 51 CD children undergoing HSCT were used to establish a PPK model based on a nonlinear mixed-effect model. Steady-state concentrations of tacrolimus for children weighing less than 20 kg treated with different dose regimens were simulated by the Monte Carlo method...

OBJECTIVE: Prophylaxis with posaconazole (PP) is effective in the prevention of invasive fungal infections in immunocompromised adult patients. However, evaluation of its effectiveness and safety in children is limited. The aim of the study was to describe the use of posaconazole as antifungal prophylaxis in children. METHODS: We reviewed the medical records of immunocompromised patients younger than 13 years with hematologic diseases and post hematopoietic stem cell transplant (HSCT) who received antifungal PP at the Instituto Nacional de Salud del Niño San Borja (INSN-SB) in Lima, Peru, from January 2014 to December 2018...