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Antimicrobial Agents and Chemotherapy, August 2005, p. 3297-3301, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3297-3301.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Correspondence of In Vitro and In Vivo Fluconazole Dose-Response Curves for Cryptococcus neoformans

Robert A. Larsen,1* Madeline Bauer,1 Ann M. Thomas,2 Alejandro Sanchez,1 Diane Citron,1 Meri Rathbun,1,{dagger} and Thomas S. Harrison3

Department of Medicine (Infectious Diseases), University of Southern California, Los Angeles, California,1 Department of Statistics, University of Northern Colorado, Greeley, Colorado,2 St. Georges Hospital Medical School, London, England3

Received 14 April 2005/ Returned for modification 25 April 2005/ Accepted 11 May 2005

We conducted in vitro experiments to evaluate the susceptibility of a clinical isolate of Cryptococcus neoformans to a wide range of concentrations of fluconazole. In vitro susceptibility was tested using broth macrodilution methods modified to provide a numeric count of viable organisms. The association between the quantitative in vitro response and fluconazole drug concentrations was estimated using local nonparametric regression. Regression analysis was used to assess the correspondence between the in vitro fluconazole concentration-response curve and the murine dose-response curve observed in our previously reported murine model. The regression model was then used to predict the murine response. There was a strong correspondence between in vitro measures of response to fluconazole alone and the previously reported biologic effects seen in the mouse. In vitro antifungal drug susceptibility testing can reliably predict the murine response to fluconazole.

* Corresponding author. Mailing address: Department of Medicine (Infectious Diseases), 2020 Zonal Ave., IRD Room 620, MC 9520, University of Southern California, Los Angeles, CA 90033. Phone: (323) 226-7556. Fax: (323) 226-2775. E-mail: rlarsen{at}usc.edu.

{dagger} Present address: Whittier Health Center, Whittier, CA.

Antimicrobial Agents and Chemotherapy, August 2005, p. 3297-3301, Vol. 49, No. 8
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.8.3297-3301.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Larsen, R. A., Bauer, M., Brouwer, A. E., Sanchez, A., Thomas, A. M., Rajanuwong, A., Chierakul, W., Peacock, S. J., Day, N., White, N. J., Rinaldi, M. G., Harrison, T. S. (2007). In Vitro-Clinical Correlations for Amphotericin B Susceptibility in AIDS-Associated Cryptococcal Meningitis. Antimicrob. Agents Chemother. 51: 343-345 [Abstract] [Full Text]  
  • Dannaoui, E., Abdul, M., Arpin, M., Michel-Nguyen, A., Piens, M. A., Favel, A., Lortholary, O., Dromer, F., the French Cryptococcosis Study Group, (2006). Results obtained with various antifungal susceptibility testing methods do not predict early clinical outcome in patients with cryptococcosis.. Antimicrob. Agents Chemother. 50: 2464-2470 [Abstract] [Full Text]  


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