Cure of orthopaedic infection with Scedosporium prolificans, using voriconazole plus terbinafine, without the need for radical surgery

Abstract

Scedosporium prolificans infections of normal hosts usually require extensive debridement and sometimes amputation to effect cure, due to the intrinsic resistance of this species to available antifungal agents. Newer agents have not tested favourably. Variable results are obtained with voriconazole, and 100% resistance is described with echinocandins. Itraconazole and terbinafine has offered synergy against various moulds including S. prolificans. In vivo success is reported with the azole/terbinafine combination in S. apiospermum pulmonary infection and Pythium insidiosum periorbital cellulitis. We report a case of orthopaedic infection in a non-immunocompromised host with S. prolificans, in which the combinations of itraconazole/terbinafine and voriconazole/terbinafine showed synergy in vitro, and success was achieved without radical surgery, using voriconazole and terbinafine.

Lomentospora prolificans vertebral osteomyelitis with spinal epidural abscess in an immunocompetent woman: Case report and literature review

“…A combination of terbinafine and voriconazole or itraconazole showed a synergistic effect against L. prolificans isolates [12] , in which both agents inhibited an ergosterol synthesis of fungal cell wall at different sites of action [11] . Anecdotal data showed the combined voriconazole and terbinafine was used to treat a patient who had L. prolificans osteoarticular infection of the left ankle successfully [13] . However, the opitmal dosing regimen and duration of antifungal therapy are still unknown.…”

Scedosporium prolificansSeptic Arthritis and Osteomyelitis of the Hip Joints in an Immunocompetent Patient: A Case Report and Literature Review

“…Reports have seen success with older antifungal agents including Amphotericin B, Ketoconazole, Miconazole, nystatin, 5-fluorocytosine, and fluconazole [3, 10, 11]. Three previous reports have demonstrated satisfactory results with newer antifungal agents Terbinafine/Voriconazole in immunocompetent patients with septic arthritis [12–15]. Another report has shown success in an 8-year-old immunocompetent patient using Hexadecylphosphocholine with Voriconazole/Terbinafine [16].…”

Terbinafine in Combination with Other Antifungal Agents for Treatment of Resistant or Refractory Mycoses: Investigating Optimal Dosing Regimens Using a Physiologically Based Pharmacokinetic Model

“…The complementary mechanisms of action of terbinafine and azoles, which inhibit squalene epoxidase and lanosterol 14␣-demethylase, respectively, theoretically result in dual inhibition of fungal ergosterol production (29). These synergistic relationships are particularly important in the treatment of multiresistant Scedosporium prolificans; several case reports have demonstrated in vitro synergy for terbinafine with other agents despite resistance to all available antifungals, leading to successful combination therapy (30)(31)(32)(33). However, the choice of antifungal agents should be made cautiously, as in vitro antagonistic interactions have been observed for both terbinafine and azoles when combined with amphotericin B for several isolates of Aspergillus fumigatus (6).…”