Egger Matthias, Bellmann Romuald, Krause Robert, Boyer Johannes, Jakšić Daniela, Hoenigl Martin
Division of Infectious Diseases, Department of Internal Medicine, Medical University of Graz, Graz, Austria.
Biotechmed-Graz, Graz, Austria.
Infect Drug Resist. 2023 Apr 12;16:2167-2178. doi: 10.2147/IDR.S372546. eCollection 2023.
Invasive mold diseases are devastating systemic infections which demand meticulous care in selection, dosing, and therapy monitoring of antifungal drugs. Various circumstances regarding PK/PD properties of the applied drug, resistance/tolerance of the causative pathogen or host intolerability can lead to failure of the initial antifungal therapy. This necessitates treatment adaption in the sense of switching antifungal drug class or potentially adding another drug for a combination therapy approach. In the current state of drastically limited options of antifungal drug classes adaption of therapy remains challenging. Current guidelines provide restricted recommendations only and emphasize individual approaches. However, novel antifungals, incorporating innovative mechanisms of action, show promising results in late stage clinical development. These will expand options for salvage therapy in the future potentially as monotherapy or in combination with conventional or other novel antifungals. We outline current recommendations for salvage therapy including PK/PD considerations as well as elucidate possible future treatment options for invasive aspergillosis and mucormycosis.
侵袭性霉菌病是严重的全身性感染,在抗真菌药物的选择、剂量确定及治疗监测方面需要精心护理。与所用药物的药代动力学/药效学特性、致病病原体的耐药性/耐受性或宿主不耐受性相关的各种情况,都可能导致初始抗真菌治疗失败。这就需要在更换抗真菌药物类别或可能添加另一种药物进行联合治疗的意义上调整治疗方案。在抗真菌药物类别选择极其有限的当前状态下,治疗调整仍然具有挑战性。当前指南仅提供有限的建议,并强调个体化方法。然而,具有创新作用机制的新型抗真菌药物在后期临床开发中显示出有希望的结果。这些药物未来可能会扩大挽救治疗的选择,可作为单一疗法或与传统或其他新型抗真菌药物联合使用。我们概述了挽救治疗的当前建议,包括药代动力学/药效学考虑因素,并阐明侵袭性曲霉病和毛霉病未来可能的治疗选择。