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American Journal of Health-System Pharmacy, Vol. 63, Issue 19, 1813-1820
Copyright © 2006 by American Society of Health-System Pharmacists
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Clinical Reviews

Echinocandins in the management of invasive fungal infections, part 2

Michele I. Morris and Mark Villmann

MICHELE I. MORRIS, M.D., FACP, is Assistant Professor of Clinical Medicine, Division of Infectious Diseases, School of Medicine, University of Miami, Miami, FL. MARK VILLMANN, PHARM.D., is Scientific Liaison, Infectious Diseases Division, Astellas Pharma US, Plantation, FL; at the time of writing he was Clinical Pharmacist, Infectious Diseases, Jackson Memorial Hospital, Miami.

Address correspondence to Dr. Morris at the Division of Infectious Diseases, School of Medicine, University of Miami, 1400 N.W. 10th Avenue, D90-A, Dominion Tower 812A, Miami, FL 33136 (mmorris2{at}med.miami.edu).


Purpose. The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effects, drug interactions, dosage and administration, cost, and place in therapy of echinocandins are reviewed.

Summary. Three echinocandins are currently available: caspofungin, micafungin, and anidulafungin. The principal mechanism of action of the echinocandins is the noncompetitive inhibition of ß-(1,3)-D-glucan synthase, an essential component of the cell wall of many fungi that is not present in mammalian cells. Echinocandins exhibit fungicidal activity against Candida species, including triazole-resistant isolates, and fungistatic activity against Aspergillus species. While fungistatic against mold, echinocandins may hold promise for the treatment of these pathogens when given in combination with amphotericin B or broad-spectrum triazoles, such as voriconazole. To date, resistance to echinocandins has been reported in only two patients. Echinocandins exhibit concentration-dependent activity against Candida species. In clinical trials, caspofungin has demonstrated efficacy in treating candidemia, esophageal candidiasis, and febrile neutropenia. Micafungin has demonstrated efficacy as antifungal prophylaxis in hematopoietic stem cell transplant recipients and in the treatment of esophageal candidiasis. Anidulafungin received approved labeling from the Food and Drug Administration in February 2006. Clinical efficacy data will be forthcoming.

Conclusion. Echinocandins are fungicidal against yeast and fungistatic against mold. Their limited toxicity profile and minimal drug–drug interactions make them an attractive new option for the treatment of invasive fungal infections. Their cost may limit their use as initial therapy for patients with fungemia in medical centers or intensive care units with a high rate of triazoleresistant Candida infections.

Index terms: Anidulafungin; Antifungals; Caspofungin; Combined therapy; Concentration; Costs; Dosage; Drug administration; Drug interactions; Mechanism of action; Micafungin; Mycoses; Pharmacodynamics; Pharmacokinetics; Resistance; Spectrum microbial; Toxicity

 






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