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.The larval stage of Echinococcus multilocularis causes alveolar echinococcosis (AE). Surgical resection of hepatic lesions is often incomplete due to the diffuse infiltration into nonresectable structures or insufficient safety margins (7).Benzimidazoles (i.e., mebendazole and albendazole) are the only drugs licensed for the treatment of unresectable AE (6). These drugs have a parasitostatic effect on E. multilocularis metacestodes. Adverse reactions lead to treatment interruptions in up to 10% of cases (3,25), and treatment failure has been reported in 16% of patients (4). The overall success rate ranges somewhere between 55 and 97% (19, 25). In cases with treatment failure the disease will ultimately progress to death.New chemotherapeutic strategies against AE are needed, because alternative treatments have been tested with very limited success (11,14,21,30). Recently, suppression of parasite growth with amphotericin B (AMB) was demonstrated in an in vitro tissue culture model (26). We now report on the first three AE patients treated long-term with AMB. MATERIALS AND METHODSAMB deoxycholate treatment. After a loading dose of 0.5 mg/kg of body weight daily for the first 2 weeks, patients were treated as outpatients and were given AMB three times per week intravenously. For better tolerance of the drug 1 liter of isotonic...

Innovative chemotherapeutical treatment options for alveolar and cystic echinococcosis

“…A major limitation of cAMB is its mode of administration (intravenous), which makes it unsuitable for prolonged use, except for salvage treatment (Reuter et al 2003 b). Also, the effect of cAMB is only parasitostatic and the drug is nephrotoxic, limiting its widespread use.…”

Immunoglobulin G Subclass Responses to Recombinant Em18 in the Follow-Up of Patients with Alveolar Echinococcosis in Different Clinical Stages

“…AE is staged according to the World Health Organization (WHO)-PNM (P, parasitic mass in the liver; N, involvement of neighboring organs; M, metastasis) system (10). Radical resection of parasitic lesions is the preferred treatment (1), but most patients are inoperable at the time of diagnosis (5,13). In a recent serological study, immunoglobulin G (IgG) antibodies directed against Em18, Em10, and Em2plus antigen compositions showed a close relationship between the clinical status and the treatment of patients with AE (16).…”

In Vitro Activities of Itraconazole, Methiazole, and Nitazoxanide versus Echinococcus multilocularis Larvae

“…As an alternative, conventional amphotericin B desoxycholate (cAMB) effectively inhibits larval growth (20). However, its effect is only parasitostatic, and wide use is limited primarily by nephrotoxicity (17).…”

“…The confirmation of in vivo efficacy and the determination of the optimal dosage will be a task for upcoming studies in animals and humans. ITZ would offer several advantages over cAMB, which is the only alternative drug shown to be effective against AE in humans in case of intolerance of benzimidazoles (17). Nephrotoxicity might impede the long-term application of cAMB and, due to the parasitostatic effect, the discontinuation of the drug is associated with the risk of relapses.…”