High-Dose Amphotericin B Lipid Complex (ABLC) for Treatment of Invasive Aspergillosis and Zygomycosis.



INTRO: ABLC is less nephrotoxic than amphotericin B making it an attractive treatment option for invasive aspergillosis and zygomycosis where high-doses are required. Although the recommended maximum dose of ABLC is 5 mg/kg/day, some patients may not respond at this dose. We describe one such case and review experience to date with high-dose ABLC (>= 6.0 mg/kg/day). CASE: A 71 year-old man with steroid-dependent glomerulonephritis developed invasive pneumonia with Aspergillus fumigatus and was given ABLC 5 mg/kg/day. His pneumonia progressed and ABLC was increased to 8 mg/kg/day, after which he improved considerably. He received a total dose of 18,575 mg over 34 days. Although his serum creatinine increased from 2.0 mg/dL to 4.1 mg/dL during treatment, he was also receiving trimethoprim/ sulfamethoxazole for concomitant pulmonary nocardiosis. METHODS: We queried the database of the Collaborative Exchange of Antifungal Research (CLEARTM}). CLEARTM} is a national registry regarding the pharmacoepidemiology of invasive fungal infections treated with ABLC. It contains information collected retrospectively on 929 patients between January 1996 and October 1997. RESULTS: Including our patient, forty-two (4.5%) received high- dose ABLC. Of these, 13 (31%) were treated for invasive aspergillosis (11) or zygomycosis (2). Ten (77%) had pulmonary or rhinocerebral involvement. Underlying diseases included leukemia (5), lymphoma (2), renal disease (2), organ transplantation (2), vasculitis (1), and diabetes mellitus (1). Patients received a daily dose (median and range) of 6.6 mg/kg (6.2 to 8.5 mg/kg). The change in serum creatinine (median and range) during therapy was +0.4 mg/dL (-0.9 to 2.1 mg/dL). Only 3 patients had an increase in serum creatinine of more than 1.0 mg/dL; all received concomitant nephrotoxic agents. Seven patients (54%) were improved or stable at the end of therapy; their duration of therapy (median and range) was 26 days (5 to 80 days). The 6 who failed were treated for 13 days (4 to 73 days). Only one death occurred during therapy (day 21) in a patient with leukemia and disseminated aspergillosis. CONCLUSION: At doses up to 8.5 mg/kg/day, ABLC appears to have minimal nephrotoxicity in the absence of other nephrotoxic agents. It is unclear if efficacy is improved, however.

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38th Interscience Conference on Antimicrobial Agents and Chemotherapy
    • ICAAC 38th