Abstract
Invasive pulmonary aspergillosis remains an important cause of morbidity and mortality among transplant recipients and patients receiving cancer chemotherapy. The lipid-associated formulation of amphotericin B (AmB), AmB lipid complex (ABLC), was evaluated for its prophylactic efficacy when it was administered as an aerosol in a rat model of pulmonary aspergillosis. Aerosol ABLC (aero-ABLC), in doses from 0.4 to 1.6 mg/kg of body weight given 2 days before infection, significantly delayed mortality compared to the mortality of rats given placebo (P < 0.001). At day 10 postinfection, 50% of rats in the 0.4-mg/kg group and 75% of rats in the 1.6-mg/kg group were alive, while all control animals had died. In a second trial aero-ABLC was more effective than an equivalent dose of aerosol AmB (aero-AmB) in prolonging survival, with 100% survival at day 14 postinfection in the ABLC group, compared to 62.5% survival in the AmB group. Mean concentrations of AmB in lungs were 3.7 times higher at day 1 (P < 0.002) and almost six times higher at day 7 (P < 0.001) after treatment with aero-ABLC than after treatment with a similar dose of aero-AmB. We conclude that aero-ABLC provided higher and more prolonged levels of the parent compound in the lungs than aero-AmB and was more effective in delaying mortality from aspergillosis in this model.
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- Allen S. D., Sorensen K. N., Nejdl M. J., Durrant C., Proffit R. T. Prophylactic efficacy of aerosolized liposomal (AmBisome) and non-liposomal (Fungizone) amphotericin B in murine pulmonary aspergillosis. J Antimicrob Chemother. 1994 Dec;34(6):1001–1013. doi: 10.1093/jac/34.6.1001. [DOI] [PubMed] [Google Scholar]
- Beyer J., Barzen G., Risse G., Weyer C., Miksits K., Dullenkopf K., Huhn D., Siegert W. Aerosol amphotericin B for prevention of invasive pulmonary aspergillosis. Antimicrob Agents Chemother. 1993 Jun;37(6):1367–1369. doi: 10.1128/aac.37.6.1367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Christiansen K. J., Bernard E. M., Gold J. W., Armstrong D. Distribution and activity of amphotericin B in humans. J Infect Dis. 1985 Nov;152(5):1037–1043. doi: 10.1093/infdis/152.5.1037. [DOI] [PubMed] [Google Scholar]
- Clark J. M., Whitney R. R., Olsen S. J., George R. J., Swerdel M. R., Kunselman L., Bonner D. P. Amphotericin B lipid complex therapy of experimental fungal infections in mice. Antimicrob Agents Chemother. 1991 Apr;35(4):615–621. doi: 10.1128/aac.35.4.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gondal J. A., Swartz R. P., Rahman A. Therapeutic evaluation of free and liposome-encapsulated amphotericin B in the treatment of systemic candidiasis in mice. Antimicrob Agents Chemother. 1989 Sep;33(9):1544–1548. doi: 10.1128/aac.33.9.1544. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gryn J., Goldberg J., Johnson E., Siegel J., Inzerillo J. The toxicity of daily inhaled amphotericin B. Am J Clin Oncol. 1993 Feb;16(1):43–46. doi: 10.1097/00000421-199302000-00011. [DOI] [PubMed] [Google Scholar]
- Lopez-Berestein G., Bodey G. P., Fainstein V., Keating M., Frankel L. S., Zeluff B., Gentry L., Mehta K. Treatment of systemic fungal infections with liposomal amphotericin B. Arch Intern Med. 1989 Nov;149(11):2533–2536. [PubMed] [Google Scholar]
- Meyer R. D., Young L. S., Armstrong D., Yu B. Aspergillosis complicating neoplastic disease. Am J Med. 1973 Jan;54(1):6–15. doi: 10.1016/0002-9343(73)90077-6. [DOI] [PubMed] [Google Scholar]
- Niki Y., Bernard E. M., Schmitt H. J., Tong W. P., Edwards F. F., Armstrong D. Pharmacokinetics of aerosol amphotericin B in rats. Antimicrob Agents Chemother. 1990 Jan;34(1):29–32. doi: 10.1128/aac.34.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Donnell M. R., Schmidt G. M., Tegtmeier B. R., Faucett C., Fahey J. L., Ito J., Nademanee A., Niland J., Parker P., Smith E. P. Prediction of systemic fungal infection in allogeneic marrow recipients: impact of amphotericin prophylaxis in high-risk patients. J Clin Oncol. 1994 Apr;12(4):827–834. doi: 10.1200/JCO.1994.12.4.827. [DOI] [PubMed] [Google Scholar]
- Schmitt H. J., Bernard E. M., Häuser M., Armstrong D. Aerosol amphotericin B is effective for prophylaxis and therapy in a rat model of pulmonary aspergillosis. Antimicrob Agents Chemother. 1988 Nov;32(11):1676–1679. doi: 10.1128/aac.32.11.1676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomas D. A., Myers M. A., Wichert B., Schreier H., Gonzalez-Rothi R. J. Acute effects of liposome aerosol inhalation on pulmonary function in healthy human volunteers. Chest. 1991 May;99(5):1268–1270. doi: 10.1378/chest.99.5.1268. [DOI] [PubMed] [Google Scholar]