An epidemic of invasive fungal infection in a stem cell transplant unit; response to high-dose liposomal amphotericin B

Novel antifungal agents as salvage therapy for invasive aspergillosis in patients with hematologic malignancies: posaconazole compared with high-dose lipid formulations of amphotericin B alone or in combination with caspofungin

“…10 Several studies have suggested that a high-dose lipid formulation of amphotericin B (HD-LPD/AMB; 10 mg kg À1 per day) improves the survival rate in patients with invasive aspergillosis. [11][12][13][14][15][16] Anecdotal experience at our institution supported these studies' findings and this led to the widespread use of HD-LPD/AMB as salvage treatment for invasive aspergillosis in hematologic malignancy patients. 17 In addition, in vitro studies suggesting that the echinocandin caspofungin has synergistic activity with amphotericin B for at least half of the Aspergillus isolates tested 18 and clinical studies showing that this combination had a response rate exceeding 55% in patients with invasive aspergillosis 19,20 led to our use of HD-LPD/AMB plus caspofungin.…”

“…11,12 Furthermore, anecdotal clinical reports have suggested that HD-LPD/AMB is safe, well tolerated and associated with a relatively high response rate (greater than 55%) in patients with invasive aspergillosis. [13][14][15][16] Walsh et al 13 reported that patients with invasive pulmonary invasive aspergillosis who received HD-LPD/AMB (X7.5 mg kg À1 per day) had an overall response rate of 71%, and Ryan et al 15 reported a 75% response rate to HD-LPD/AMB among eight patients with invasive aspergillosis who had hematologic malignancies. In a prospective, randomized study that compared regular-dose LPD/AMB plus caspofungin (3 mg kg À1 per day) with HD-LPD/AMB (10 mg kg À1 per day) in 30 patients with invasive aspergillosis, HD-LPD/AMB monotherapy was associated with an 86% response rate, whereas the Table 6 Renal and hepatic toxicity related to salvage therapy Toxicity HD-LPD/AMB (n ¼ 52) …”

“…This unexpectedly low response rate might be related to several factors. First, compared with earlier studies, [13][14][15][16] the current study included a sicker population of hematologic malignancy patients, most of whom were neutropenic at the onset of infection and almost half of whom had undergone hematopoietic stem cell transplant. In addition, 78% of the transplant patients who received HD-LPD/AMB had graft-versus-host disease.…”