CHRONIC SCEDOSPORIUM OSTEOMYELITIS: A DECADE-LONG BATTLE AND A NEW THERAPEUTIC HOPE

AIM To present a case of chronic osteomyelitis caused by Scedosporium apiospermium, highlighting the therapeutic challenge of this rare condition. Scedosporium is a fungus that can cause severe disease in immunocompromised patients, with high mortality, and compartmentalized infections following direct inoculation in immunocompetent individuals. Until recently, an effective treatment for scedosporiasis was virtually unavailable. METHOD This case report describes a 47-year-old woman followed since 2010 at the Infectious Diseases Department of S. Orsola Hospital and the Orthopedic Oncology Department of the Rizzoli Institute in Bologna for post-traumatic chronic osteomyelitis of the left tibia caused by Scedosporium. The initial trauma occurred in Thailand during the 2004 tsunami. RESULTS Between 2010 and 2020, the patient, otherwise healthy, underwent six debridement procedures and received multiple antifungal treatments, including voriconazole (2010), posaconazole and terbinafine (2011), isavuconazole (2018), and isavuconazole plus terbinafine (2020). However, pain and fistulas recurred each time. In November 2023, she underwent resection of the left tibia (approximately 15 cm from the proximal end) and placement of a cement spacer, with the long-term goal of internal prosthesis implantation. Postoperatively, antifungal treatment with oral olorofim (150 mg every 12 hours for two doses, then 90 mg every 12 hours) was initiated on a compassionate use basis, alongside intravenous daptomycin and fosfomycin. Of 11 intraoperative biopsy samples, 8 tested positive for Scedosporium. Following the culture results, daptomycin and fosfomycin were discontinued, and treatment continued with olorofim alone. In February and April 2024, two further surgical procedures with cement spacer replacement were carried out. Olorofim (90 mg BID) was continued. In both instances, Scedosporium was isolated from intraoperative samples and sonicated cement. Thanks to the collaboration of the drug's manufacturer, a sensitivity test for olorofim was conducted on the Scedosporium strains isolated in November and February, with MIC values suggesting full sensitivity. Based on these results, in agreement with the pharmaceutical company, the olorofim dosage was increased from June 2024, first to 120 mg BID, then to 150 mg BID. On 26th February 2025, the patient underwent a fourth spacer exchange and debridement. For the first time, all intraoperative biopsy samples and sonicated cement were microbiologically negative. Olorofim has been well tolerated, with no adverse events or abnormalities in blood tests. Since November 2023, neither fistulas nor pain have recurred. CONCLUSION This case highlights the importance of a multidisciplinary approach and the potential role of newer antifungal therapies, such as olorofim, in managing Scedosporium-related infections.