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.
Highlights
Fracture-related infection (FRI) is a challenging and severe complication in musculoskeletal trauma surgery, especially in cases of open fractures [1,2]
We describe a case of A. fumigatus FRI following a bifocal open tibia and fibula fracture in which isavuconazole was used as salvage therapy
Articles were included if a conclusive diagnosis of Aspergillus osteomyelitis, including FRI, or spondylodiscitis was reported and information was given on the administered systemic antifungal treatment
Summary
Fracture-related infection (FRI) is a challenging and severe complication in musculoskeletal trauma surgery, especially in cases of open fractures [1,2]. Infection incidences up to 30% have been reported in cases of severe injury [2]. FRI is predominantly caused by direct inoculation of microorganisms during trauma or during the insertion of orthopedic devices [1]. Staphylococcus aureus, coagulase-negative staphylococci and Enterobacterales are the most commonly isolated microorganisms causing FRI [1]. FRI caused by fungi, such as the Candida and Aspergillus species, are rare [3–7]. Until today, the term ‘Aspergillus FRI’ has not been described in the literature as a separate entity [8]
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