Salvage Therapy for Alveolar Echinococcosis—A Case Series

Abstract

Benzimidazoles are the only approved drugs for the treatment of inoperable human alveolar echinococcosis but may be limited due to intolerance or, rarely, ineffectiveness. A medical second-line or salvage therapy is not available, though it is urgently needed. We report long-term follow-up data from 14 patients who underwent salvage therapy with repurposed drugs with cumulatively 53.25 patient-years. Treatment response was evaluated by both clinical outcome and image studies, preferably PET/CT. Eleven patients received amphotericin B, and 70% of evaluable cases showed some positive treatment response, but side effects often limited therapy. Five patients received nitazoxanide, of which two showed clear progression but one achieved a lasting stable disease. One patient was treated with mefloquine combination therapy in advanced disease, and overall, a positive treatment response could not be assessed. Furthermore, we report on one patient receiving pembrolizumab for a concomitant malignancy, which did not result in a reduction of echinococcal manifestation. In summary, current options of salvage therapy can sometimes induce persistent disease control, although with potentially significant side effects and high treatment costs, and mortality remains high. No clear recommendation for a salvage therapy can be given; treatment remains highly experimental, and non-pharmaceutical interventions have to be considered.

Case Report: Amphotericin B and Mefloquine as a Salvage Treatment of Alveolar Echinococcosis

“…Only one patient treated with mefloquine in combination with ABZ and AmBD has been reported, with no treatment response after 7 months. 13 Although avoidance of palliative surgery is advised whenever possible, 3 in the case of our patient, it was performed to alleviate symptoms, need for repeated hospitals admissions (pleural effusions and recurring bacteremia episodes), and deterioration of the patient's condition despite pharmacological therapy. However, because palliative surgery can result in a worse outcome than pharmacological therapy alone, it is important to carefully choose patients who can benefit from the procedure.…”

“…This regimen was chosen owing to in vitro kinetics studies that showed the cycling effect and possible prolonged suppressive effect on parasite growth. 12 Recently, Burkert et al 13 reported the largest series yet, comprising 11 patients treated with different AmBD formulations and dosing regimens. Of these, three had stable disease, three had clear progression, and six developed nephrotoxicity requiring treatment cessation or reduction of dosage.…”

“…Interestingly, the authors suggested possible differences in treatment outcomes with liposomal and non-liposomal formulations; 43% of patients treated with liposomal formulations had treatment failure. 13 Because of its parasitostatic effect, AmBD treatment should be lifelong, requires intravenous application, and can be inconvenient for some patients. In addition, long-term use can cause adverse effects such as nephrotoxicity and hepatotoxicity.…”

Investigation of the mechanism of action of mefloquine and derivatives against the parasite Echinococcus multilocularis

“…When used in malaria prophylaxis, mefloquine can induce strong neuropsychiatric side-effects ( Tickell-Painter et al, 2017 ). A first clinical report of an AE patient that was treated with MEF did not lead to a positive treatment response, but no adverse effects did occur either ( Burkert et al, 2022 ). This further confirms the potential lack of parasiticidal activity of MEF in an in vivo setting.…”