Introduction: Invasive fungal infections represent an expanding threat to public health. The recent emergence of Candida auris, which is often resistant to existing antifungal agents and is associated with a high mortality rate, underscores the urgent need for novel drug development strategies.
Areas covered: In this paper, we examine both challenges and opportunities associated with antifungal drug development and explore potential avenues to accelerate the development pipeline, including data sharing, surrogate endpoints, and the role of historical controls in clinical trials.
Expert commentary: We review important lessons learned from the study of other rare diseases, including mitochondrial storage diseases and certain forms of cancer that may inform strategies to develop new antifungal agents while highlighting promising new compounds such as SCY-078 for the treatment of invasive fungal infections. 相似文献
Invasive mold infections continue to account for significant morbidity and mortality in immunocompromised patients; outcomes are dependent on both underlying host factors and appropriate therapy. The antifungal armamentarium has gradually increased during the past, with liposomal amphotericin B (L-AMB) being an important representative. Still, the question of what dose to use – a maximum tolerated or a minimum effective – has yet to be answered. On this basis, a randomized trial comparing a high-loading dose regimen with a standard dosing of L-AMB (AmBiLoad trial) for primary therapy of mold infections was initiated. No significant differences in response between the treatment groups were detected, although recipients of the 10-mg/kg daily dose experienced higher rates of nephrotoxicity and hypokalemia. Uncontrolled malignancy and allogeneic stem cell transplantation were significantly associated with poor survival. This article analyzes the study, discusses the rationale and the results and concludes that this study supports the routine application of L-AMB. 相似文献
Introduction: Invasive candidiasis is responsible for ~ 10% of nosocomial sepsis in very-low-birth-weight infants and is associated with substantial morbidity and mortality. Over the last two decades, the antifungal armamentarium against Candida spp. has increased; however, efficacy and safety studies in this population are lacking.
Areas covered: We reviewed the medical literature and extracted information on clinical and observational studies evaluating the use of antifungal agents in neonates with invasive candidiasis.
Expert opinion: Efficacy and safety data for antifungals in neonates are lacking, and the majority of studies conducted to date have concentrated on pharmacokinetic/pharmacodynamic evaluations. Unlike other anti-infective agents, efficacy data in the setting of neonatal candidiasis cannot be extrapolated from adult studies due to differences in the pathophysiology of the disease in this population relative to older children and adults. Data for amphotericin B deoxycholate, fluconazole, and micafungin suggest that these are the current agents of choice for this disease in neonates until data for newer antifungal agents become available. For prophylaxis, data from fluconazole randomized controlled trials will be submitted to the regulatory agencies for labeling. Ultimately, the field of therapeutics for neonatal candidiasis will require multidisciplinary collaboration given the numerous challenges associated with conducting clinical trials in neonates. 相似文献