Impact of antimicrobial dosing regimen on evolution of drug resistance in vivo:: Fluconazole and Candida albicans

被引:59
作者
Andes, D.
ForreSt, A.
Lepak, A.
Nett, J.
Marchillo, K.
Lincoln, L.
机构
[1] Univ Wisconsin, Dept Med, Madison, WI 53792 USA
[2] Univ Wisconsin, Dept Med Microbiol & Immunol, Madison, WI 53792 USA
[3] SUNY Buffalo, Sch Pharm, Buffalo, NY 14260 USA
关键词
D O I
10.1128/AAC.01053-05
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Numerous factors have been theorized to affect the development of antimicrobial resistance, including those specific to the host, the organism, the environment, the drug, and the drug prescriber. One variable under the control of the prescriber is the drug dosing regimen. Dosing regimens can vary in dose level, dosing interval, and treatment duration. The current studies examined the relationships between antimicrobial dosing regimens and resistance development by use of an in vivo model. A murine model of systemic Candida albicans infection was used to examine resistance emergence during exposure to the triazole antifungal fluconazole. Data from this experimental model demonstrated that the more frequently administered dosing prevented selection of the isogenic resistant cell populations. Conversely, dosing regimens producing prolonged sub-MIC effects appeared to contribute to the outgrowth of isogenic resistant strains. The association between dosing and resistance emergence observed in the current investigation is disparate from that described for antimicrobial compounds with cidal killing characteristics. The inhibitory or static antimicrobial activity of the triazole compounds may explain these differences.
引用
收藏
页码:2374 / 2383
页数:10
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