Caspofungin and liposomal amphotericin B therapy of experimental murine scedosporiosis

Abstract

Immunosuppressed mice were infected intravenously with conidia of Scedosporium prolificans. Treatment was begun 1 day later with liposomal amphotericin B, caspofungin, or both drugs initiated concurrently. Amphotericin B and caspofungin were each effective, but combined therapy did not appear to offer advantages over liposomal amphotericin B alone.

FIG. 1.

Survival of mice infected with S. prolificans and treated with various antifungal agents. (A) Mice were infected i.v. with 2.4 × 10⁵ conidia/mouse (low dose of inoculum) and treated days 1 to 10 postchallenge. Controls received 0.2 ml sterile water i.p. Liposomal amphotericin B (LAMB) was given i.v. at 10, 20, or 30 mg/kg. (B) Caspofungin (CAS) was given i.p. at 5, 10, or 20 mg/kg. (C) Mice were infected i.v. at 2.3 × 10⁶ conidia/mouse (high dose of inoculum) and treated from days 1 to 10 postchallenge. Controls received 0.2 ml sterile water i.p. Liposomal amphotericin B was given i.v. at 10, 20, or 30 mg/kg. (D) Caspofungin was given i.p. at 5, 10, or 20 mg/kg. Caspofungin at 5 mg/kg was not effective. (E) In this survival study, mice were infected i.v. at 2.4 × 10⁵ conidia/mouse (low dose of inoculum). Therapy was administered days 1 to 10 postchallenge. Controls received 0.2 ml sterile distilled water i.p. Caspofungin was given i.p. at 20 mg/kg alone and in combination with liposomal amphotericin B. Liposomal amphotericin B was given i.v. at 30 mg/kg alone and in combination with caspofungin.

FIG. 2.

Burden of S. prolificans in kidney tissue treated with various antifungal agents. (A) Mice were infected i.v. with 2.7 × 10⁵ conidia/mouse and treated days 1 to 7 postchallenge. Controls received 0.2 ml sterile water i.p. Caspofungin (CAS) was given i.p. at 20 mg/kg alone and in combination with liposomal amphotericin B (LAMB). Liposomal amphotericin B was given i.v. at 30 mg/kg alone and in combination with caspofungin. (B) In this study, mice were infected with a sublethal dose of 8.7 × 10⁴ conidia/mouse and treated with lower doses of liposomal amphotericin B at 10 or 20 mg/kg, caspofungin at 20 mg/kg, or combined therapy.