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Antimicrobial Agents and Chemotherapy, December 1999, p. 2841-2847, Vol. 43, No. 12
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Interaction between Fluconazole and Amphotericin B in Mice with Systemic Infection Due to Fluconazole-Susceptible or -Resistant Strains of Candida albicans

Arnold Louie,1,2,* Partha Banerjee,1,2 George L. Drusano,1,3 Mehdi Shayegani,2 and Michael H. Miller1,3

Division of Infectious Diseases1 and Clinical Pharmacology,3 Department of Medicine, Albany Medical College, Albany, New York 12208, and Wadsworth Center, New York State Department of Health, Albany, New York 122012

Received 10 July 1998/Returned for modification 13 December 1998/Accepted 8 September 1999

The interaction between fluconazole (Flu) and amphotericin B (AmB) was evaluated in a murine model of systemic candidiasis for one Flu-susceptible strain (MIC, 0.5 µg/ml), two strains with intermediate Flu resistance (Flu mid-resistant strains) (MIC, 64 and 128 µg/ml), and one highly Flu-resistant strain (MIC, 512 µg/ml) of Candida albicans. Differences in fungal densities in kidneys of infected mice after 24 h of therapy and in survival rates at 62 days of mice treated with an antifungal drug or a combination of antifungal drugs for 4 days were compared. For the Flu-susceptible and Flu mid-resistant strains, the combination of Flu and AmB was antagonistic, as shown by both quantitative culture results and survival. The interaction was additive for the highly Flu-resistant strain. These results suggest that the combination of Flu and AmB should be used with caution in infections due to fungi that are usually susceptible to both antifungal agents and as empirical antifungal drug therapy.

* Corresponding author. Mailing address: Division of Infectious Diseases, Mail Code-49, Albany Medical College, 47 New Scotland Ave., Albany, NY 12208. Phone: (518) 262-6548. Fax: (518) 262-6727. E-mail: arnold_louie_at_amc01-3{at}ccgateway.amc.edu.

Antimicrobial Agents and Chemotherapy, December 1999, p. 2841-2847, Vol. 43, No. 12
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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