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Antimicrobial Agents and Chemotherapy, November 2002, p. 3499-3505, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3499-3505.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antifungal Activity of Amphotericin B, Fluconazole, and Voriconazole in an In Vitro Model of Candida Catheter-Related Bloodstream Infection

Russell E. Lewis,1,2* Dimitrios P. Kontoyiannis,1,2 Rabih O. Darouiche,3 Issam I. Raad,1 and Randall A. Prince1,2,3

University of Houston College of Pharmacy,1 The University of Texas M. D. Anderson Cancer Center,2 Baylor College of Medicine, Houston, Texas3

Received 12 December 2001/ Returned for modification 24 March 2002/ Accepted 15 August 2002

The activity of five simulated antifungal regimens for eradication of catheter-related bloodstream Candida infection was evaluated with an in vitro pharmacodynamic model. Single-lumen central venous catheters were colonized with Candida species by sequentially incubating central venous catheters in plasma and then in growth medium (RPMI plus morpholinepropanesulfonic acid) containing a standardized suspension (105 CFU/ml) of Candida albicans, Candida glabrata, or slime-producing Candida parapsilosis. Colonized central venous catheters were then placed in a one-compartment pharmacodynamic model where five antifungal regimens (plus control) were simulated: amphotericin B, 1.0 mg/kg every 24 h; amphotericin B, 0.5 mg/kg every 24 h; fluconazole, 400 mg every 24 h; fluconazole, 800 mg every 24 h; and voriconazole, 4 mg/kg every 12 h. During exposure to the simulated clinical regimens, samples were serially removed from the model over 48 h for quantitation of viable organisms. All antifungal regimens suppressed fungal counts by both peripheral and catheter sampling versus control (P = 0.001). Overall, antifungal activity ranked amphotericin B (1 mg/kg) > amphotericin B (0.5 mg/kg) >= voriconazole > fluconazole (800 mg) >= fluconazole (400 mg). No regimen, however, completely eradicated (by culture and electron microscopy) central venous catheter colonization. Regrowth was noted in the model during therapy against C. glabrata and C. parapsilosis but was not associated with an increase in the MICs for the isolates. Lack of in vitro antifungal activity against biofilm-encased organisms appeared to be the primary reason for mycological failure of antifungal regimens in the model.

* Corresponding author. Mailing address: 1441 Moursund St. #423, Texas Medical Center, Houston TX 77030. Phone: (713) 795-8326. Fax: (713) 795-8383. E-mail: rlewis{at}uh.edu.

Antimicrobial Agents and Chemotherapy, November 2002, p. 3499-3505, Vol. 46, No. 11
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.11.3499-3505.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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