Lipid‐based amphotericin in pulmonary zygomycosis: safety and efficacy of high exposure in a renal allograft recipient

Abstract

Zygomycosis is associated with a high mortality in immunosuppressed patients. Treatment typically includes surgical resection and administration of intravenous amphotericin B. Success of treatment may require withdrawal of immunosuppression, with risk of graft loss. We report the successful treatment of invasive pulmonary zygomycosis, following initial surgical resection, using very high doses of lipid-based amphotericin B without withdrawal of immunosuppression. The patient received daily doses up to 10 mg/kg/day (51 g cumulatively) of lipid-based amphotericin B along with a brief course of intrapleural amphotericin. Despite immunosuppression not being withdrawn, the patient's kidney allograft function remained stable. We conclude that high doses of lipid-based amphotericin B can be safe and effective as part of the treatment regimen for pulmonary zygomycosis.

Pseudohyperphosphatemia associated with high-dose liposomal amphotericin B therapy

“…This lipid formulation has a favorable toxicity profile when compared to conventional amphotericin B deoxycholate [2][3][4] and has been approved for use at dosages ranging from 3 to 6 mg/kg/day for indications including empirical therapy of persistent febrile neutropenia, systemic aspergillus, candida, and cryptococcus infections, visceral leishmaniasis, and cryptococcal meningitis in HIV infected patients. The improved safety and tolerability of this formulation have allowed for the use of increasingly higher dosages for the treatment of refractory infections [5][6][7][8]. However, a single case in the pediatric literature reported severe hyperphosphatemia related to therapy with 25 mg/kg/day of L-AMB [9].…”

Cunninghamella bertholletiae Infection in Children

“…27,28 Favorable outcomes with adjuvant intrapleural AmB have been reported in adults with proven pulmonary mucormycosis and extensive pleural or chest wall involvement. 29,30 In children, intrapleural AmB was reported in a 12-year-old immunocompromised boy with proven pleuropulmonary and central nervous system aspergillosis. 31 No serious side-effects were reported either in adults or children with intrapleural AmB.…”

Lipid formulations of amphotericin B as first-line treatment of zygomycosis

“…Their efficacy appears to be comparable to or better than that of AmB deoxycholate [8]. These lipid formulations of AmB have been used in the treatment of zygomycosis with consistently successful outcomes [43,44,49–53] and therefore are considered as drugs of choice for this disease [52]. AmB lipid formulations should be used at a dose starting at 3–5 mg/kg/day, although higher doses will be needed occasionally.…”

“…In a murine model of disseminated Rhizopus oryzae infection in mice with diabetic ketoacidosis, high‐dose L‐AmB (15 mg/kg/day) was considerably more effective than AmB deoxycholate (1 mg/kg/day), nearly doubling the survival rate [66]. Although the optimal dose and duration of treatment with L‐AmB has not been established and the recommended dose for other invasive fungal infections is 3 mg/kg, in most cases it has been used in doses of 5–15 mg/kg/day and for a duration of ≤6 months [39,51,53,57,61–63,67–70].…”