TY - JOUR
T1 - Efficacy of unilamellar liposomal amphotericin b in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits
T2 - The potential role of bronchoalveolar d-mannitol and serum galactomannan as markers of infection
AU - Francis, Peter
AU - Lee, James W.
AU - Hoffman, Alan
AU - Peter, Joanne
AU - Francesconi, Andrea
AU - Bacher, John
AU - Shelhamer, James
AU - Pizzo, Philip A.
AU - Walsh, Thomas J.
PY - 1994/2
Y1 - 1994/2
N2 - A model of primary pulmonary aspergillosis in rabbits was developed to reproduce the persistent levels of profound granulocytopenia and the histopathologic features of bronchopneumonia, vascular invasion, and hemorrhagic infarction encountered in humans. d-mannitol was detectable in bronchoalveolar lavage fluid by gas-liquid chromatography/mass spectroscopy, and galactomannan was measurable in serum by latex agglutination immunoassay. A pharmacokinetically distinctive unilamellar vesicle formulation of liposomal amphotericin B, 5 mg/kg/day intravenously, compared with high-dose conventional desoxycholate amphotericin B, 1 mg/kg/day intravenously, was more effective in preventing nephrotoxicity, increasing survival, reducing the number of viable organisms, and decreasing tissue injury due to Aspergillus organisms. Thus, d-mannitol in lavage fluid and galactomannan in serum may be useful markers of pulmonary aspergillosis, and liposomal amphotericin B was significantly more effective and safer than desoxycholate amphotericin B for treatment of pulmonary aspergillosis in profoundly granulocytopenic rabbits.
AB - A model of primary pulmonary aspergillosis in rabbits was developed to reproduce the persistent levels of profound granulocytopenia and the histopathologic features of bronchopneumonia, vascular invasion, and hemorrhagic infarction encountered in humans. d-mannitol was detectable in bronchoalveolar lavage fluid by gas-liquid chromatography/mass spectroscopy, and galactomannan was measurable in serum by latex agglutination immunoassay. A pharmacokinetically distinctive unilamellar vesicle formulation of liposomal amphotericin B, 5 mg/kg/day intravenously, compared with high-dose conventional desoxycholate amphotericin B, 1 mg/kg/day intravenously, was more effective in preventing nephrotoxicity, increasing survival, reducing the number of viable organisms, and decreasing tissue injury due to Aspergillus organisms. Thus, d-mannitol in lavage fluid and galactomannan in serum may be useful markers of pulmonary aspergillosis, and liposomal amphotericin B was significantly more effective and safer than desoxycholate amphotericin B for treatment of pulmonary aspergillosis in profoundly granulocytopenic rabbits.
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U2 - 10.1093/infdis/169.2.356
DO - 10.1093/infdis/169.2.356
M3 - Article
C2 - 8106769
AN - SCOPUS:0028140216
SN - 0022-1899
VL - 169
SP - 356
EP - 368
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 2
ER -