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Chapter 32 : Echinocandins in the Treatment of Aspergillosis
Category: Clinical Microbiology; Fungi and Fungal Pathogenesis
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In the presence of caspofungin, blunting and abnormal branching of the hyphae in actively growing areas of the cell are observed, primarily at the tips and branching points. These observations are consistent with the mechanism of action but do not fit the classical definitions of a fungicidal or fungistatic agent. Echinocandins are large molecules with a relative molecular weight of approximately 1,200. Due to their large molecule size and poor oral bioavailability (less than 10%), echinocandins are available for parenteral administration only. Recently, the European Organization for Research and Treatment of Cancer reported on their multicenter clinical trial that evaluated caspofungin as first-line treatment for proven and probable invasive aspergillosis in 61 evaluable patients with hematological cancer. Four compassionate use studies conducted prior to licensure in several different countries showed that caspofungin produced favorable responses in a variety of patients with invasive aspergillosis, most of whom demonstrated refractoriness to or intolerance of prior systemic antifungal therapy. Initial reports of combination therapy in invasive aspergillosis have focused on refractory disease. Echinocandins are generally very well tolerated both in the healthy subjects of the clinical pharmacology studies and in patients with a wide spectrum of diseases and receiving many concomitant medications who were included in the clinical trials. In clinical studies of patients with invasive aspergillosis, caspofungin and micafungin are well-tolerated for prolonged treatment durations (up to 162 days for caspofungin), and the favorable safety profile was maintained with extended therapy.
Key Concept Ranking
- Fungal Infections
Comparison of echinocandins in adults