Isavuconazole in childrens

Invasive fungal disease (IFD) remains a significant cause of morbidity and mortality in children undergoing transplantation. There is a growing armamentarium of novel antifungal agents recently approved for use or in late stages of clinical development. The overarching goal of this review is to discuss the mechanisms of action, spectrum of activity, stage of development, and pediatric-specific data for the following agents: encochleated amphotericin B deoxycholate, fosmanogepix, ibrexafungerp, isavuconazole, olorofim, opelconazole, oteseconazole, and rezafungin...

Isavuconazole (ISA) is approved for treating invasive aspergillosis and mucormycosis in adults, but its use in children remains off-label. We report on the use of ISA in real-world pediatric practice with 15 patients receiving ISA for treatment of invasive fungal infections. Therapeutic drug monitoring (TDM) was performed in all patients, with 52/111 (46.8%) Ctrough determinations out of range, thus supporting the need for TDM in children, especially those receiving extracorporeal membrane oxygenation (ECMO)...

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...

BACKGROUND AND PURPOSE: Given the high mortality rate of invasive candidiasis in hospitalized pediatric patients, it is crucial to establish a predictive system to achieve early diagnosis and treatment of patients who are likely to benefit from early antifungal treatment. This study aimed to assess the Candida colonization index, species distribution, and antifungal susceptibility pattern of Candida strains isolated from pediatric patients with high Candida colonization index (CI). MATERIALS AND METHODS: This study was carried out at the Children's Medical Center in Tehran-Iran...

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...

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%)...

Isavuconazole is a broad-spectrum azole anti-fungal not yet approved in children. We conducted a retrospective, single-center review of isavuconazole use and routine therapeutic drug monitoring in pediatric patients, extracting demographic, dosing, concentration, mortality and hepatoxicity data. We constructed a nonparametric population model using Pmetrics. Of 26 patients, 19 (73%) were male. The mean (SD) age and weight were 12.7 (5.5) years and 50.9 (26.8) kg. Eighty percent received between 9.7 and 10.6 mg/kg per dose...

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...

BACKGROUND: Limited evidence concerning optimal azole dosing regimens currently exists for antifungal prophylaxis in hemato-oncological pediatric patients. METHODS: Hemato-oncological children receiving intravenous or oral isavuconazole or voriconazole for primary antifungal prophylaxis at IRCCS Azienda Ospedaliero-Universitaria of Bologna during November 2020 to October 2021 and undergoing CPA programs based on real-time therapeutic drug monitoring (TDM) were retrospectively analyzed...

This work's objective was to evaluate the safety of isavuconazole (ISA) as a treatment or prophylaxis for invasive fungal infections (IFIs) in immunocompromised children. IFI was reported as proven or probable according to international definitions. Therapeutic drug monitoring was performed using mass tandem spectrometry to quantify trough plasma concentrations. Targeted ISA levels were 2-4 mg/L, as reported in adult series. Nine patients received ISA as a curative treatment, and six received ISA as prophylaxis...

Introduction: Antimicrobial treatment is quite common among hospitalized children. The dynamic age-associated physiological variations coupled with the pathophysiological alterations caused by underlying illness and potential drug-drug interactions makes the implementation of appropriate antimicrobial dosing extremely challenging among paediatrics. Therapeutic drug monitoring (TDM) may represent a valuable tool for assisting clinicians in optimizing antimicrobial exposure. Clinical pharmacological advice (CPA) is an approach based on the correct interpretation of the TDM result by the MD Clinical Pharmacologist in relation to specific underlying conditions, namely the antimicrobial susceptibility of the clinical isolate, the site of infection, the pathophysiological characteristics of the patient and/or the drug-drug interactions of cotreatments...

A previously healthy 9-year-old girl developed fulminant myocarditis due to severe influenza A infection complicated with methicillin-resistant Staphylococcus aureus pneumonia, requiring extracorporeal membrane oxygenation (ECMO) support. Twelve days after admission, Aspergillus fumigatus was isolated in tracheal aspirate, and 12 h later she suddenly developed anisocoria. Computed tomography (CT) of the head showed fungal brain lesions. Urgent decompressive craniectomy with lesion drainage was performed; histopathology found hyphae in surgical samples, culture-positive for Aspergillus fumigatus (susceptible to azoles, echinocandins, and amphotericin B)...

Triazoles represent an important class of antifungal drugs in the prophylaxis and treatment of invasive fungal disease in pediatric patients. Understanding the pharmacokinetics of triazoles in children is crucial to providing optimal care for this vulnerable population. While the pharmacokinetics is extensively studied in adult populations, knowledge on pharmacokinetics of triazoles in children is limited. New data are still emerging despite drugs already going off patent. This review aims to provide readers with the most current knowledge on the pharmacokinetics of the triazoles: fluconazole, itraconazole, voriconazole, posaconazole, and isavuconazole...

BACKGROUND: Mucormycosis is a rare but emerging life-threatening fungal disease with limited treatment options. Isavuconazole is a new triazole that has shown efficacy in adults for primary and salvage treatment of mucormycosis. However, data in children are scarce. METHODS: The demographic and clinical data of pediatric patients with proven mucormycosis who were treated with isavuconazole in 2015 to 2019 at 2 centers were collected. RESULTS: Four children of median age 10...

We analyzed the use of isavuconazole (ISA) as treatment or prophylaxis for invasive fungal disease (IFD) in children with hemato-oncologic diseases. A multicentric retrospective analysis was performed among centers belonging to the Italian Association for Pediatric Hematology and Oncology (AIEOP). Pharmacokinetic (PK) monitoring was applied by a high-performance liquid chromatography-tandem mass spectrometry (HLPC-MS/MS) assay. Twenty-nine patients were studied: 10 during chemotherapy and 19 after allogeneic hematopoietic stem cell transplantation (HSCT)...

BACKGROUND: The use of isavuconazole is approved for the management of invasive aspergillosis and mucormycosis, only in adults, as no paediatric pharmacology studies have been reported to date. Very few paediatric cases have been published concerning the use of isavuconazole. Amphotericin B is the only antifungal agent recommended in paediatric mucormycosis, but adverse effects and especially nephrotoxicity, even with the liposomal formulation, could be problematic. In this context, the use of other antifungal molecules active on Mucorales becomes needful...

BACKGROUND: Invasive mucormycosis is a rare but frequently fatal fungal disease. The acute and rapidly progressive evolution causes unfavourable outcome in 22%-59% of patients and its treatment represents a clinical challenge, especially in immunocompromised patients. Current data in paediatric oncological patients are limited. OBJECTIVES: The infection Working Group of the Italian Association of Pediatric Hematology and Oncology (AIEOP) analysed the episodes of invasive mucormycosis occurred between 2009 and 2016...

The main indications for antifungal drug administration in pediatrics are reviewed as well as an update of the data of antifungal agents and antifungal policies performed. Specifically, antifungal therapy in three main areas is updated as follows: a) Prophylaxis of premature neonates against invasive candidiasis; b) management of candidemia and meningoencephalitis in neonates; and c) prophylaxis, empiric therapy, and targeted antifungal therapy in children with primary or secondary immunodeficiencies. Fluconazole remains the most frequent antifungal prophylactic agent given to high-risk neonates and children...

Invasive mucormycosis in immunocompromised children is a life-threatening fungal infection. We report a case of a 7-year-old girl treated for acute lymphoblastic leukaemia complicated by disseminated mucormycosis during induction therapy. Microscopic examination of surgically removed lung tissue revealed wide, pauci-septate hyphae suggesting a Mucorales infection. This diagnosis was confirmed immunohistochemically and by PCR analysis followed by a final identification of Cunninghamella sp. The patient was treated successfully with surgical debridement and antifungal combination therapy with amphotericin B, caspofungin and isavuconazole...

BACKGROUND: Invasive mold infections (IMIs) are a leading cause of mortality among immunocompromised patients. Isavuconazole is a new drug that shows promise in the adult population for the treatment of IMIs. No data regarding the use of isavuconazole in pediatric patients have been published. METHODS: Patients with a diagnosis of IMI from our pediatric hemato-oncology division, treated with isavuconazole between 2010 and 2016, were identified using the hospital's computerized database...