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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...

Invasive fungal diseases are important clinical problems that are often complicated by severe illness and therefore the inability to use invasive measures to definitively diagnose the disease. Tests for a range of fungal biomarkers that do not require an invasive sample-collection procedure have been incorporated into adult clinical practice, but pediatric data and pediatric-specific recommendations for some of these diagnostic tools are lacking. In this review, we summarize the published...

Aspergillus species are ubiquitous fungi that infect humans after their asexual spores are inhaled and deposited in the respiratory tract. Neutrophils and cell-mediated immunity are crucial components of host defenses that prevent invasion of Aspergillus, and these elements are often lacking or impaired in transplant recipients. Aspergillosis is the most common invasive fungal infection in hematopoietic stem cell transplant recipients and the second most common in solid organ transplant...

Infectious complications are a major cause of morbidity and mortality in patients undergoing solid organ or stem cell transplantation. Over the past years, advances in immunology and molecular biology have greatly contributed to a better understanding of the pathogenesis of opportunistic infections in the immunocompromised host. The lifelong immunosuppression required by the transplant recipients together with the limitations of the current anti-infective agents makes strategies able to...

Infections of the central nervous system (ICNS) contribute significantly to morbidity and mortality in patients receiving solid organ and stem cell transplants. The risk for ICNS is influenced by multiple factors, including the organ transplanted, type and degree of immunosuppression, post-transplant adverse events, as well as donor characteristics. These infections may be classified by anatomic location – intracranial, spinal, and paraspinal – as well as by time of onset. The early...

Infections are major complications in pediatric patients undergoing hematopoietic stem cell or solid organ transplantation. They also represent the most significant barrier to short- and long-term survival of the transplanted allograft. The achievements and advances during the past 30 years have resulted in remarkably improved outcome for pediatric patients undergoing transplantation. These advances in pediatric infectious disease supportive care have contributed substantially to the...

Antifungal prophylaxis can prevent invasive fungal diseases (IFDs) in high-risk, immunocompromised patients. This study assessed real-world use of mold-active triazoles (MATs) for the prevention of IFDs.This subgroup analysis of a multicenter, observational, prospective registry in the US from March 2017 to April 2020 included patients who received MATs for prophylaxis (isavuconazole, posaconazole, and voriconazole) at study index/enrollment. The primary objective was to describe patient...

In this randomized trial of patients undergoing treatment for acute myelogenous leukemia or the myelodysplastic syndrome, prophylaxis with posaconazole resulted in fewer fungal infections and longer survival than did prophylaxis with fluconazole or itraconazole. The difference was primarily due to a lower rate of invasive aspergillosis in the posaconazole group.

Abstract. It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician

It is important to realize that guidelines cannot always account for individual variation among patients. They are not intended to supplant physician judgment with respect to particular patients or special clinical situations. IDSA considers adherence to these guidelines to be voluntary, with the ultimate determination regarding their application to be made by the physician in the light of each patient's individual circumstances.

In recent years, the global public health community has increasingly recognized the importance of antimicrobial stewardship (AMS) in the fight to improve outcomes, decrease costs, and curb increases in antimicrobial resistance around the world. However, the subject of antifungal stewardship (AFS) has received less attention. While the principles of AMS guidelines likely apply to stewarding of antifungal agents, there are additional considerations unique to AFS and the complex field of fungal...

Sargramostim (yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]) augments innate and adaptive immune responses and accelerates hematopoietic recovery of chemotherapy-induced neutropenia. However, considerably less is known about its efficacy as adjunctive immunotherapy against invasive fungal diseases (IFDs).The clinical courses of 15 patients with pediatric malignancies and IFDs treated adjunctively with sargramostim at a single...

BACKGROUND: Invasive aspergillosis (IA) is associated with poor outcomes in patients with hematologic malignancies (HMs) and hematopoietic cell transplantation (HCT). Small studies suggest a role for combination antifungal therapy. OBJECTIVE: To assess the safety and efficacy of voriconazole and anidulafungin compared with voriconazole monotherapy for treatment of IA. DESIGN: Randomized, double-blind, placebo-controlled multicenter trial. (ClinicalTrials.gov: NCT00531479). SETTING: 93...

Rising antimicrobial resistance rates may impact the efficacy of empirical antibiotic treatment for febrile neutropenia in high-risk cancer patients. Lacking contemporary data about the epidemiology, antibiotic resistance patterns, and clinical outcomes from bloodstream infections (BSIs) in US cancer patients, it is unclear if current guidelines remain relevant.In a cross-sectional study, 14 US cancer centers prospectively identified BSIs in high-risk febrile neutropenic (FN) patients,...

Invasive fungal infection (IFI) is a serious threat after allogeneic hematopoietic cell transplant (HCT). This multicenter, randomized, double-blind trial compared fluconazole (N = 295) versus voriconazole (N = 305) for the prevention of IFI in the context of a structured fungal screening program. Patients undergoing myeloablative allogeneic HCT were randomized before HCT to receive study drugs for 100 days, or for 180 days in higher-risk patients. Serum galactomannan was assayed twice...

Invasive fungal diseases (IFDs) remain important causes of morbidity and mortality. The consensus definitions of the Infectious Diseases Group of the European Organization for Research and Treatment of Cancer and the Mycoses Study Group have been of immense value to researchers who conduct clinical trials of antifungals, assess diagnostic tests, and undertake epidemiologic studies. However, their utility has not extended beyond patients with cancer or recipients of stem cell or solid organ...