Abstract：
Aspergillus fracture-related infection (FRI) is a rare, but severe complication in trauma surgery. The optimal antifungal treatment for Aspergillus osteomyelitis, including FRI, has not been established yet, as only cases have been documented and data on bone penetration of antifungal drugs are scarce. We describe a patient with Aspergillus fumigatus FRI of the tibia who was treated with isavuconazole after developing liver function disturbances during voriconazole therapy. Isavuconazole, the active moiety formed after hydrolysis of the prodrug isavuconazonium sulfate by plasma esterases, was administered in a maintenance dose of 200 mg q24 h, followed by 150 mg q24 h. The patient completed a six-month antifungal treatment course. Although fracture union was not achieved during six months of follow-up after therapy cessation, no confirmatory signs of FRI were observed. Additionally, two literature searches were conducted to review available data on antifungal treatment of Aspergillus osteomyelitis and bone penetration of antifungals. One hundred and eight cases of Aspergillus osteomyelitis, including six (5.6%) FRI cases, were identified. Voriconazole and (lipid formulations of) amphotericin B were the most commonly used antifungals. In three (2.8%) cases isavuconazole was prescribed as salvage therapy. Data on antifungal bone penetration were reported for itraconazole, voriconazole, amphotericin B, anidulafungin and 5-fluorocytosin. Isavuconazole might be a promising alternative for the treatment of Aspergillus osteomyelitis. However, standardized case documentation is needed to evaluate the efficacy of isavuconazole and other antifungals in the treatment of Aspergillus osteomyelitis, including FRI.
摘要：
曲霉菌骨折相关性感染（FRI）是一种罕见的，而是创伤手术的严重并发症.曲霉菌骨髓炎的最佳抗真菌治疗方法，包括FRI,尚未建立，因为只有病例被记录，关于抗真菌药物骨渗透的数据很少。我们描述了一名患有胫骨烟曲霉FRI的患者，该患者在伏立康唑治疗期间出现肝功能紊乱后接受了伊沙康康唑治疗。伊沙武康唑,通过血浆酯酶水解前药isavuconazonsulate后形成的活性部分，以200毫克q24小时的维持剂量给药，然后是150mgq24h。患者完成了为期六个月的抗真菌治疗过程。尽管在停止治疗后的6个月随访期间未实现骨折愈合，未观察到FRI的确证征象.此外,本研究进行了两次文献检索,目的是回顾有关曲霉菌骨髓炎的抗真菌治疗和抗真菌药物的骨渗透的现有数据.108例曲霉骨髓炎,包括六例(5.6%)FRI病例，已确定。伏立康唑和两性霉素B（脂质制剂）是最常用的抗真菌药。在3例（2.8％）中，以阿武康唑被规定为挽救疗法。报告了伊曲康唑抗真菌骨渗透的数据，伏立康唑,两性霉素B,anidulafungin和5-氟胞嘧啶。伊沙武康唑可能是治疗曲霉骨髓炎的有希望的替代药物。然而,需要标准化的病例文件来评估伊沙武康唑和其他抗真菌药物治疗曲霉骨髓炎的疗效，包括FRI。
