Journal article
Assessment of Antifungal Activities of Fluconazole and Amphotericin B Administered Alone and in Combination against Candida albicans by Using a Dynamic In Vitro Mycotic Infection Model
Antimicrobial agents and chemotherapy, Vol.42(6), pp.1382-1386
06/01/1998
DOI: 10.1128/AAC.42.6.1382
PMCID: PMC105608
PMID: 9624480
Abstract
We evaluated the pharmacodynamic activities of fluconazole and amphotericin B given alone and in combination against
Candida albicans
by using an in vitro model of bloodstream infection that simulates human serum pharmacokinetic parameters for these antifungals. Fluconazole was administered as a bolus into the model to simulate regimens of 200 mg every 24 h (q24h) and 400 mg q24h. Amphotericin B was administered at doses producing the peak concentration (2.4 μg/ml) observed with a regimen of 1 mg/kg of body weight q24h. A combination regimen of fluconazole (400 mg q24h) and amphotericin B (1 mg/kg q24h) administered simultaneously and as a staggered regimen (amphotericin B bolus given 8 h after fluconazole bolus) was also simulated in the model to characterize possible antagonism between these agents. Fluconazole alone and amphotericin B alone demonstrated fungistatic (<99.9% reduction in numbers of CFU per milliliter from the starting inoculum) and fungicidal (>99.9% reduction) activity, respectively. When fluconazole and amphotericin B were administered simultaneously, fungicidal activity similar to that observed with amphotericin B alone was observed. Staggered administration of fluconazole and amphotericin B, however, resulted in a substantial reduction of the fungicidal activity of amphotericin B, producing fungistatic activity similar to that observed with noncombination fluconazole regimens. These results demonstrate the usefulness of this model for comparing the in vitro pharmacodynamic characteristics of different antifungal regimens and support the theory of azole-polyene antagonism. The effects of this antagonism on the in vivo activity and clinical usefulness of combination antifungal therapy, however, remain to be determined.
Details
- Title: Subtitle
- Assessment of Antifungal Activities of Fluconazole and Amphotericin B Administered Alone and in Combination against Candida albicans by Using a Dynamic In Vitro Mycotic Infection Model
- Creators
- Russell E. Lewis - University of IowaBrian C. Lund - American Association of Colleges of PharmacyMichael E. Klepser - American Association of Colleges of PharmacyErika J. Ernst - American Association of Colleges of PharmacyMichael A. Pfaller - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Antimicrobial agents and chemotherapy, Vol.42(6), pp.1382-1386
- Publisher
- American Society for Microbiology
- DOI
- 10.1128/AAC.42.6.1382
- PMID
- 9624480
- PMCID
- PMC105608
- ISSN
- 0066-4804
- eISSN
- 1098-6596
- Language
- English
- Date published
- 06/01/1998
- Academic Unit
- Epidemiology; Pathology; Emergency Medicine; Pharmacy Practice and Science
- Record Identifier
- 9984365906002771
Metrics
10 Record Views