Salvage treatment with amphotericin B in progressive human alveolar echinococcosis

Abstract

Most patients with alveolar echinococcosis are diagnosed at a late stage when the disease has advanced to unresectable hepatic lesions. These patients require lifelong therapy with benzimidazoles, the only medical treatment currently available. To date, no treatment option remains for patients with benzimidazole intolerance or treatment failure. Amphotericin B was recently shown to exert antiparasitic activity in vitro. Here, we report the efficacy of amphotericin B in human alveolar echinococcosis. In three patients with extensive disease and without further treatment options, disease progression had been documented over several months. They were treated with amphotericin B intravenously at a dose of 0.5 mg/kg of body weight three times per week. Follow-up parameters were physical examination, laboratory parameters, and imaging techniques. Amphotericin B treatment effectively halted parasite growth in all three patients. The antiparasitic effect was most evident by spontaneous closure of cutaneous fistulae in two patients and by constant size of parasitic lesions during treatment, as assessed radiologically. Metabolic activity in parasitic areas was visualized by positron emission tomography and significantly decreased during treatment. However, progressive affection of the heart in one patient could not be stopped. All patients currently continue on amphotericin B and have been treated for 25, 17, and 14 months, respectively. We introduce amphotericin B as salvage treatment for alveolar echinococcosis patients with intolerance or resistance to benzimidazoles, as it effectively suppresses parasite growth. Amphotericin B is not parasitocidal; therefore long-term treatment has to be anticipated.

FIG. 1.

AE of the sternum with involvement of the subcutaneous tissue and cutaneous fistulation. The fistula was draining purulent liquid before AMB treatment (a) and was completely closed 4 months later (b). Viable E. multilocularis larvae were found in the aspirate from the fistulae when it was injected into Mongolian gerbils.

FIG. 2.

Progressive disease was noted on MRI in patient 2 during benzimidazole treatment between July 2001 and January 2002 (a and b, left images). During progression, intense metabolic activity in the parasitic area was shown on FDG-PET (b, right image). At this point AMB treatment was initiated. Progression could be halted (c, left image), and metabolic activity in the parasitic area decreased (c, right image).

FIG. 3.

Sequence of FDG-PET images during AMB therapy in patient 3. The antiparasitic activity of AMB is shown by a significant reduction of metabolic activity in the parasitic area over time. The upper row shows coronal views with a metabolically active focus in the subcutaneous tissue of the ventral thoracic wall (arrows pointing right). In the lower row the same focus is depicted in a lateral view (arrows pointing left).