Efficacy of unilamellar liposomal amphotericin b in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits: The potential role of bronchoalveolar d-mannitol and serum galactomannan as markers of infection

Peter Francis, James W. Lee, Alan Hoffman, Joanne Peter, Andrea Francesconi, John Bacher, James Shelhamer, Philip A. Pizzo, Thomas J. Walsh

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)356-368
Number of pages13
JournalJournal of Infectious Diseases
Volume169
Issue number2
DOIs
StatePublished - 1994
Externally publishedYes

Fingerprint

Pulmonary Aspergillosis
Amphotericin B
Mannitol
Rabbits
Infection
Serum
Bronchopneumonia
Unilamellar Liposomes
Agranulocytosis
Therapeutic Irrigation
Agglutination
Latex
Bronchoalveolar Lavage Fluid
Aspergillus
Immunoassay
Gas Chromatography
Infarction
Blood Vessels
Mass Spectrometry
Therapeutics

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy
  • Immunology
  • Public Health, Environmental and Occupational Health

Cite this

Efficacy of unilamellar liposomal amphotericin b in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits : The potential role of bronchoalveolar d-mannitol and serum galactomannan as markers of infection. / Francis, Peter; Lee, James W.; Hoffman, Alan; Peter, Joanne; Francesconi, Andrea; Bacher, John; Shelhamer, James; Pizzo, Philip A.; Walsh, Thomas J.

In: Journal of Infectious Diseases, Vol. 169, No. 2, 1994, p. 356-368.

Research output: Contribution to journalArticle

Francis, Peter ; Lee, James W. ; Hoffman, Alan ; Peter, Joanne ; Francesconi, Andrea ; Bacher, John ; Shelhamer, James ; Pizzo, Philip A. ; Walsh, Thomas J. / Efficacy of unilamellar liposomal amphotericin b in treatment of pulmonary aspergillosis in persistently granulocytopenic rabbits : The potential role of bronchoalveolar d-mannitol and serum galactomannan as markers of infection. In: Journal of Infectious Diseases. 1994 ; Vol. 169, No. 2. pp. 356-368.
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abstract = "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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