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Antimicrobial Agents and Chemotherapy, February 2003, p. 813-815, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.813-815.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Efficacy of Amphotericin B or Itraconazole in a Murine Model of Central Nervous System Aspergillus Infection

Tom M. Chiller,1,2,3 Raymond A. Sobel,4,5 Javier Capilla Luque,1,2,3 Karl V. Clemons,1,2,3 and David A. Stevens1,2,3*

Division of Infectious Diseases, Department of Medicine, Santa Clara Valley Medical Center, San Jose, California 95128-2699,1 California Institute for Medical Research, San Jose, California 95128,2 Division of Infectious Diseases and Geographic Medicine,3 Department of Pathology, Stanford University School of Medicine, Stanford, California 94305,4 Department of Pathology, Palo Alto VA Health Care System, Palo Alto, California 943045

Received 19 July 2002/ Returned for modification 6 September 2002/ Accepted 4 November 2002

Given the greater than 90% lethality of clinical central nervous system (CNS) aspergillosis despite current therapies, there is a need for an animal model to study therapeutic strategies. We previously established a model of CNS aspergillosis by intracerebral infection and report here the results of treatment with the two therapies with the greatest clinical experience, i.e., treatments with amphotericin B (AMB) and itraconazole (ITZ). Mice were given cyclophosphamide to produce pancytopenia. AMB was given intraperitoneally (i.p.; 3 mg/kg of body weight) or intravenously (i.v.; 0.8 mg/kg) once daily. ITZ in cyclodextrin was given by gavage once daily at a dose of 100 mg/kg or twice daily at 50 mg/kg. Treatments were started at day 1 postinfection and given for 10 days. At day 15, survivors were euthanatized. Ninety percent of the mice given no treatment died by day 6, and 100% died by day 10. Mice treated with AMB either i.p. or i.v. had 40% survival. Mice treated with ITZ either once or twice per day had a median survival time of 10 days, compared with 4 days for control animals, but a survival rate of only 10%. AMB and ITZ prolonged survival (P, <0.0001 to <0.05) compared with controls. Brains from surviving mice had CFU of Aspergillus fumigatus. This model can be used to compare newer antifungals and to study combination therapy or immunotherapy to find better therapeutic alternatives.

* Corresponding author. Mailing address: Department of Medicine, Division of Infectious Diseases, Santa Clara Valley Medical Center, 751 S. Bascom Ave., San Jose, CA 95128-2699. Phone: (408) 885-4302. Fax: (408) 885-4306. E-mail: stevens{at}stanford.edu.

Antimicrobial Agents and Chemotherapy, February 2003, p. 813-815, Vol. 47, No. 2
0066-4804/03/$08.00+0     DOI: 10.1128/AAC.47.2.813-815.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Clemons, K. V., Parmar, R., Martinez, M., Stevens, D. A. (2006). Efficacy of Abelcet alone, or in combination therapy, against experimental central nervous system aspergillosis. J Antimicrob Chemother 58: 466-469 [Abstract] [Full Text]  
  • Clemons, K. V., Espiritu, M., Parmar, R., Stevens, D. A. (2005). Comparative Efficacies of Conventional Amphotericin B, Liposomal Amphotericin B (AmBisome), Caspofungin, Micafungin, and Voriconazole Alone and in Combination against Experimental Murine Central Nervous System Aspergillosis. Antimicrob. Agents Chemother. 49: 4867-4875 [Abstract] [Full Text]  
  • Imai, J., Singh, G., Fernandez, B., Clemons, K. V., Stevens, D. A. (2005). Efficacy of Abelcet and caspofungin, alone or in combination, against CNS aspergillosis in a murine model. J Antimicrob Chemother 56: 166-171 [Abstract] [Full Text]  
  • Singh, G., Imai, J., Clemons, K. V., Stevens, D. A. (2005). Efficacy of Caspofungin against Central Nervous System Aspergillus fumigatus Infection in Mice Determined by TaqMan PCR and CFU Methods. Antimicrob. Agents Chemother. 49: 1369-1376 [Abstract] [Full Text]  
  • Imai, J. K., Singh, G., Clemons, K. V., Stevens, D. A. (2004). Efficacy of Posaconazole in a Murine Model of Central Nervous System Aspergillosis. Antimicrob. Agents Chemother. 48: 4063-4066 [Abstract] [Full Text]  


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