Yazarlar : Howard SJ, Slater J, Sharp A, Goodwin J, Gregson L, Alastruey-Izquierdo A, Perlin DS, Warn PA, Hope WW.

Yayın : Antimicrob Agents Chemother.

Yayın Yılı : 2011

Pubmed Linki : http://www.ncbi.nlm.nih.gov/pubmed/21807969

Konu : Enfeksiyon

Literatür İçeriği :  

Abstract

Candida glabrata is a leading cause of disseminated candidiasis. The echinocandins are increasingly used as first-line agents for the treatment of patients with this syndrome, although the optimal regimen for the treatment of invasive Candida glabrata infections in neutropenic patients is not known. We studied the pharmacokinetics and pharmacodynamics of micafungin, anidulafungin and caspofungin in a neutropenic murine model of disseminated Candida glabrata infection to gain a further insight into optimal therapeutic options for patients with this syndrome. A mathematical model was fitted to the data and the used to bridge the experimental results to humans. The intravenous inoculation of Candida glabrata in mice was followed by logarithmic growth throughout the experimental period (101 hours). A dose-dependent decline in fungal burden was observed following the administration of 0.1-20 mg/kg every 24 hours for all three agents. The exposure-response relationships for each drug partitioned into distinct fungistatic and fungicidal components of activity. Surprisingly, the average human drug exposures following currently licensed regimens were predicted to only result in a fungistatic antifungal effect. Higher human dosages of all three echinocandins are required to induce fungicidal effects in neutropenic hosts.

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