Pharmacodynamics of echinocandins against Candida glabrata: requirement for dosage escalation to achieve maximal antifungal activity in neutropenic hosts.
نویسندگان
چکیده
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 (PK) and pharmacodynamics (PD) of micafungin, anidulafungin, and caspofungin in a neutropenic murine model of disseminated Candida glabrata infection to gain further insight into optimal therapeutic options for patients with this syndrome. A mathematical model was fitted to the data and 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 h). A dose-dependent decline in fungal burden was observed following the administration of 0.1 to 20 mg/kg of body weight every 24 h 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 result in a fungistatic antifungal effect. Higher human dosages of all three echinocandins are required to induce fungicidal effects in neutropenic hosts.
منابع مشابه
In vivo Pharmacokinetic/Pharmacodynamic (PK/PD) Target Characterization of the Novel, Long Acting Echinocandin CD101 against C. albicans and C. glabrata in the Neutropenic Murine Disseminated Candidiasis Model
متن کامل
Treatment of fungal disease in the setting of neutropenia.
Invasive fungal infections are important causes of morbidity and attributable mortality in neutropenic patients with hematological malignancies, myelodysplasia, and aplastic anemia. Successful risk-based strategies can be implemented for prophylaxis, empirical therapy, and preemptive therapy for the prevention and early treatment of invasive fungal infections in neutropenic hosts. The use of ec...
متن کاملAssessment of the in vitro kinetic activity of caspofungin against Candida glabrata.
Echinocandins have become the drug of choice in infections caused by Candida glabrata. The objective of this study was to evaluate the in vitro activity of caspofungin alone and in combination against C. glabrata. In vitro assays demonstrated that caspofungin alone showed excellent fungicidal activity against C. glabrata, including fluconazole-resistant strains. The combination of caspofungin a...
متن کاملIn vitro Antifungal Effect of Aqueous Garlic (Allium Sativum) Extract and its Combination with Fluconazole Against Five Common Clinical Candida Isolated from Candidiasis Lesions
Introduction: Increasing rate of candidiasis prevalence and consequently use of antifungal drugs as prophylactic and curative agents has led to the widespread emergence of resistant strains. Therefore this study was designed to evaluate the in vitro antifungal activity of an aqueous extract of garlic and the synergic effect of garlic extract with fluconazole against common clinical isolates of ...
متن کاملCurrent treatment strategies for disseminated candidiasis.
The incidence of disseminated candidiasis has increased dramatically over the past several decades. Fortunately, in recent years, a variety of new antifungal agents have become available to treat these infections. On the basis of efficacy, safety, and cost considerations, fluconazole is the agent of choice for the empirical treatment of disseminated candidiasis in nonneutropenic, hemodynamicall...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 55 10 شماره
صفحات -
تاریخ انتشار 2011