This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Olson, J. A.
Right arrow Articles by Proffitt, R. T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Olson, J. A.
Right arrow Articles by Proffitt, R. T.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2006, p. 2122-2131, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00315-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Comparative Efficacies, Toxicities, and Tissue Concentrations of Amphotericin B Lipid Formulations in a Murine Pulmonary Aspergillosis Model

Jon A. Olson,1 Jill P. Adler-Moore,1* Julie Schwartz,2 Gerard M. Jensen,3 and Richard T. Proffitt4

Department of Biological Sciences, California State Polytechnic University, Pomona, California 91768,1 Pathology Associates Division, Charles River Laboratories, Inc., Davis, California 95616,2 Gilead Sciences, Inc., 650 Cliffside Drive, San Dimas, California 91773,3 RichPro Associates, 2095 Lavender Hill Court, Lincoln, CA 956484

Received 13 March 2006/ Returned for modification 14 March 2006/ Accepted 17 March 2006

Invasive aspergillosis, an important cause of morbidity and mortality in immunosuppressed (IS) patients, is often treated with amphotericin B lipid formulations. In the present study, liposomal amphotericin B (L-AMB) and amphotericin B lipid complex (ABLC) were compared in treatment of murine pulmonary aspergillosis. Uninfected, IS mice were treated for 4 days with 1, 4, 8, or 12 mg L-AMB or ABLC/kg of body weight, and their lungs were analyzed by high-performance liquid chromatography for drug concentrations. IS mice intranasally challenged with Aspergillus fumigatus were treated with 12, 15, or 20 mg/kg L-AMB or ABLC and monitored for survival, fungal burden (CFU), and tissue drug concentration. Blood urea nitrogen (BUN) levels and kidney histopathology were determined for uninfected and infected mice given 15 or 20 mg/kg L-AMB or ABLC. The results showed that both drugs had therapeutic levels of drug (>3.0 µg/g) in the lungs of uninfected or infected mice, and 24 h after the last dose, ABLC levels were significantly higher than L-AMB levels (P < 0.02). L-AMB and ABLC at 12 mg/kg both produced 57% survival, but only L-AMB at 15 or 20 mg/kg further increased survival to 80 to 90%, with BUN levels and kidney morphology similar to those of controls. Survival at 15 or 20 mg/kg ABLC was not significantly different than that of controls, and BUN levels were significantly elevated, with tubular alterations in uninfected animals and acute necrosis in kidney tubules of infected animals. In conclusion, although both drugs were effective in prolonging survival at 12 mg/kg, the reduced nephrotoxicity of L-AMB increased its therapeutic index, allowing for its safe and effective use at 15 or 20 mg/kg.

* Corresponding author. Mailing address: Department of Biological Sciences, California State Polytechnic University, Pomona, CA 91768. Phone: (909) 869-4047. Fax: (909) 869-4048. E-mail: jpadler{at}csupomona.edu.

Antimicrobial Agents and Chemotherapy, June 2006, p. 2122-2131, Vol. 50, No. 6
0066-4804/06/$08.00+0     doi:10.1128/AAC.00315-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Ellis, M., Bernsen, R., Ali-Zadeh, H., Kristensen, J., Hedstrom, U., Poughias, L., Bresnik, M., Al-Essa, A., A. Stevens, D. (2009). A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever. J Med Microbiol 58: 1474-1485 [Abstract] [Full Text]  
  • Gubbins, P. O., Amsden, J. R., McConnell, S. A., Anaissie, E. J. (2009). Pharmacokinetics and Buccal Mucosal Concentrations of a 15 Milligram per Kilogram of Body Weight Total Dose of Liposomal Amphotericin B Administered as a Single Dose (15 mg/kg), Weekly Dose (7.5 mg/kg), or Daily Dose (1 mg/kg) in Peripheral Stem Cell Transplant Patients. Antimicrob. Agents Chemother. 53: 3664-3674 [Abstract] [Full Text]  
  • Odabasi, Z., Karaalp, A., Cermik, H., Mohr, J., Tigen, E. T., Koc, M., Korten, V. (2009). Reduction of Amphotericin B-Induced Renal Tubular Apoptosis by N-Acetylcysteine. Antimicrob. Agents Chemother. 53: 3100-3102 [Abstract] [Full Text]  
  • Gautam, P., Shankar, J., Madan, T., Sirdeshmukh, R., Sundaram, C. S., Gade, W. N., Basir, S. F., Sarma, P. U. (2008). Proteomic and Transcriptomic Analysis of Aspergillus fumigatus on Exposure to Amphotericin B. Antimicrob. Agents Chemother. 52: 4220-4227 [Abstract] [Full Text]  
  • Lewis, R. E., Albert, N. D., Kontoyiannis, D. P. (2008). Efficacy of Single-Dose Liposomal Amphotericin B or Micafungin Prophylaxis in a Neutropenic Murine Model of Invasive Pulmonary Aspergillosis. Antimicrob. Agents Chemother. 52: 4178-4180 [Abstract] [Full Text]  
  • Vallon-Eberhard, A., Makovitzki, A., Beauvais, A., Latge, J.-P., Jung, S., Shai, Y. (2008). Efficient Clearance of Aspergillus fumigatus in Murine Lungs by an Ultrashort Antimicrobial Lipopeptide, Palmitoyl-Lys-Ala-DAla-Lys. Antimicrob. Agents Chemother. 52: 3118-3126 [Abstract] [Full Text]  
  • Olson, J. A., Adler-Moore, J. P., Jensen, G. M., Schwartz, J., Dignani, M. C., Proffitt, R. T. (2008). Comparison of the Physicochemical, Antifungal, and Toxic Properties of Two Liposomal Amphotericin B Products. Antimicrob. Agents Chemother. 52: 259-268 [Abstract] [Full Text]  
  • Smith, P. J., Olson, J. A., Constable, D., Schwartz, J., Proffitt, R. T., Adler-Moore, J. P. (2007). Effects of dosing regimen on accumulation, retention and prophylactic efficacy of liposomal amphotericin B. J Antimicrob Chemother 59: 941-951 [Abstract] [Full Text]  
  • Lewis, R. E., Liao, G., Hou, J., Chamilos, G., Prince, R. A., Kontoyiannis, D. P. (2007). Comparative Analysis of Amphotericin B Lipid Complex and Liposomal Amphotericin B Kinetics of Lung Accumulation and Fungal Clearance in a Murine Model of Acute Invasive Pulmonary Aspergillosis. Antimicrob. Agents Chemother. 51: 1253-1258 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»