Scedosporium prolificansOsteomyelitis in an Immunocompetent Child Treated with a Novel Agent, Hexadecylphospocholine (Miltefosine), in Combination with Terbinafine and Voriconazole: A Case Report

Abstract

We describe an 8-year-old girl who sustained multiple compound fractures in an accident involving agricultural equipment. She developed Scedosporium prolificans osteomyelitis of the pelvis, septic arthritis of the hip, and myositis of adjacent muscles. The infection progressed, despite extensive surgical debridement and joint washouts with 0.2% polyhexamethylene biguanide; antifungal therapy with caspofungin, terbinafine, and voriconazole; and adjunctive therapy with interferon-gamma. Gradual resolution was achieved after the addition of a novel agent, hexadecylphospocholine (miltefosine), and the continuation of terbinafine and voriconazole. This is the first report of the use of miltefosine as an antifungal agent in the management of severe infection with S. prolificans.

Melanized Fungi in Human Disease

“…There are relatively few case reports of isolated osteoarticular infections due to dematiaceous fungi, perhaps reflecting the significant trauma often required for implantation into these deeper tissues, though some cases did not have noticeable trauma. S. prolificans is the most common cause, with all except two cases occurring in young children (166,299,325,406,453,474,716,718). In addition to surgery, various antifungal therapies have been employed, with three cases using the combination of voriconazole and terbinafine with success (166,299,406).…”

“…S. prolificans is the most common cause, with all except two cases occurring in young children (166,299,325,406,453,474,716,718). In addition to surgery, various antifungal therapies have been employed, with three cases using the combination of voriconazole and terbinafine with success (166,299,406). Unusual therapies have also been tried, including irrigation with polyhexamethylbiguanide and oral therapy with miltefosine (406,716).…”

Disseminated Scedosporium / Pseudallescheria Infection after Double-Lung Transplantation in Patients with Cystic Fibrosis

“…The in vitro study of 35 antifungal combinations against S. apiospermum and S. prolificans describing a potent synergy between azole drugs and echinocandins will probably reopen the debate on combination therapy (8,23). Promising results obtained with new antifungal agents such as miltefosine remain to be confirmed (20,30). In the present case, it is interesting to note the reliability of the Etest for MIC determination for Scedosporium species, as MICs obtained by the Etest were generally correlated with those obtained by the EUCAST method, especially for voriconazole.…”

Can repurposing of existing drugs provide more effective therapies for invasive fungal infections?

“…In addition, more recently, it has been shown to have fungicidal activity against Scedosporium, Fusarium, and Mucormycetes. [18][19][20] In vitro studies have shown that miltefosine demonstrates synergistic interactions when combined with posaconazole or voriconazole against a series of uncommon filamentous fungi [20] and can also cause a significant reduction in amphotericin B and voriconazole minimum inhibitory concentrations when used against Scedosporium spp. [21] In vivo, miltefosine given orally to mice after intravenous infection with C. neoformans delayed the morbidity and mortality and reduced the cryptococcal burden in the brain.…”