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Objectives The aim of this study was to characterize voriconazole trough concentrations (Cmin) and associated hepatotoxicity, and to determine predictors of hepatotoxicity and identify high-risk groups in critically ill patients. Methods This was a nationwide, multicenter, retrospective study. We studied Cmin and hepatotoxicity in 363 critically ill patients from 2015 to 2020 who received voriconazole treatment. Logistic regression and classification and regression tree (CART) models were...

Objective: Posaconazole is used for prophylaxis and treatment of invasive fungal infections in lung transplant recipients (LTR). Previous studies have not described the relationship between elevated posaconazole trough concentrations and adverse drug reactions in this population. Methods: This IRB-approved, retrospective cohort study at NewYork-Presbyterian Hospital included LTR who had posaconazole trough concentrations measured. The primary aim of this study was to evaluate elevated...

Abstract Background Acute myeloid leukemia (AML) is associated with poor prognosis, particularly in elderly patients with comorbidities. Combining azacitidine (AZA) with BCL-2 inhibitor venetoclax (VEN) demonstrated significant improvement in outcomes for newly-diagnosed AML patients compared to AZA alone. However, this regimen is myelosuppressive, and the incidence of invasive fungal infections (IFIs) and impact of antifungal prophylaxis are not...

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...

Invasive fungal diseases due to resistant yeasts and molds are an important and increasing public health threat, likely due to a growing population of immunosuppressed hosts, increases in antifungal resistance, and improvements in laboratory diagnostics.  The significant morbidity and mortality associated with these pathogens bespeaks the urgent need for novel safe and effective therapeutics.  This review highlights promising investigational antifungal agents in clinical phases of...

Background Antifungal stewardship (AFS) has emerged as an important component of quality in managing invasive fungal infections (IFIs), and cost-benefit calculations suggest regular training in AFS is well worth the effort. Methods This review will discuss the most common IFIs in solid organ transplantation (SOT)-recipients, how to diagnose them, and current recommendations for antifungal treatment and prophylaxis before demonstrating key takeaway points of AFS in this high-risk population....

At present, there is still a lack of effective invasive fungal prophylaxis therapy in liver transplant recipients (LTRs). This study aimed to analysis the latest evidence on efficacy of current prophylactic anti-fungal therapy, and systematically compare between anti-fungal agents and placebo by a fixed-effects meta-analysis in all randomised controlled trials. A network meta-analysis was performed for invasive fungal infection (IFI) among different agents in 14 randomised controlled trials,...

Background Invasive fungal infections (IFI), particularly invasive aspergillosis (IA), cause significant morbidity and mortality in lung transplant (LTx) recipients. The optimum strategy and antifungal agents for prevention are unclear. Methods We performed a comprehensive literature search, systematic review, and network meta-analysis using a frequentist framework to compare the efficacy of various antifungal drugs on the incidence of IA/IFI in the setting of universal prophylaxis or no...

Background Antifungal stewardship (AFS) lags behind antimicrobial stewardship (AMS) in terms of implementation, evidence base, and workforce experience. Solid-organ transplantation (SOT) carries a significant risk of invasive fungal infection, with high associated mortality, and is therefore associated with significant opportunities to optimize antifungal use. Methods A literature search for the terms “antifungal stewardship” and “solid-organ transplant” revealed a small evidence base to...

Abstract Clinicians treating patients with fungal infections may turn to susceptibility testing to obtain information regarding the activity of different antifungals against a specific fungus that has been cultured. These results may then be used to make decisions regarding a patient’s therapy. However, for many fungal species that are capable of causing invasive infections, clinical breakpoints have not been established. Thus, interpretations of susceptible or resistant cannot...

This review summarizes the investigational antifungals in clinical development with the potential to address rising drug resistance patterns. The relevant pharmacodynamics, spectrum of activity, preclinical studies, and latest clinical trial data are described.

Background.  Children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) are at high risk for invasive fungal disease (IFD). Methods.  This multicenter, randomized, open-label trial planned to enroll 560 children and adolescents (3 months to <21 years) undergoing allogeneic HCT between April 2013 and September 2016. Eligible patients were randomly assigned to antifungal prophylaxis with caspofungin or a center-specific comparator triazole (fluconazole or...

Invasive fungal infections (IFIs) are associated with high mortality rates and timely appropriate antifungal therapy is essential for good outcomes. Emerging antifungal resistance among Candida and Aspergillus spp., the major causes of IFI, is concerning and has led to the increasing incorporation of in vitro antifungal susceptibility testing (AST) to guide clinical decisions. However, the interpretation of AST results and their contribution to management of IFIs remains a matter of debate....

The epidemiology of invasive fungal infections is changing, with new populations at risk and the emergence of resistance caused by the selective pressure from increased usage of antifungal agents in prophylaxis, empiric therapy, and agriculture. Limited antifungal therapeutic options are further challenged by drug–drug interactions, toxicity, and constraints in administration routes. Despite the need for more antifungal drug options, no new classes of antifungal drugs have become available...

Background. Invasive fungal disease (IFD) is a major cause of morbidity and mortality in patients after hematopoietic stem cell transplantation (HSCT). Itraconazole has been used for prevention of IFD, but data related to incidence and associated factors of IFD in pediatric and adolescent patients on itraconazole prophylaxis remain scarce. Objectives. To identify incidence and risk factors associated with IFD among pediatric and adolescent patients receiving itraconazole prophylaxis after...