RESUMEN
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 beta-(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.
Asunto(s)
Antifúngicos/uso terapéutico , Lipoproteínas/uso terapéutico , Micosis/tratamiento farmacológico , Péptidos Cíclicos/uso terapéutico , Anidulafungina , Profilaxis Antibiótica/métodos , Aspergilosis/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Caspofungina , Cateterismo/efectos adversos , Cuidados Críticos/métodos , Quimioterapia Combinada , Equinocandinas , Humanos , Lipopéptidos , Micafungina , Trasplantes/microbiologíaRESUMEN
PURPOSE: The chemistry, pharmacology, spectrum of activity, resistance, pharmacokinetics, pharmacodynamics, clinical efficacy, adverse effiects, 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 beta-(1,3)-dglucan 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.
Asunto(s)
Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Micosis/tratamiento farmacológico , Antifúngicos/clasificación , HumanosRESUMEN
BACKGROUND: In response to vancomycin-resistant bacteria, particularly vancomycin-resistant enterococci (VRE), measures have been recommended to improve on the appropriate use of vancomycin. METHODS: Intervention 1 consisted of an automatic 72-hour vancomycin stop order; Intervention 2, a standardized procedure for sampling of blood cultures; and Intervention 3, an interdisciplinary critical care team. RESULTS: After Intervention 1, inappropriate use decreased, particularly in treatment of febrile neutropenia and undocumented gram-positive infections. After Intervention 2, the baseline rate of inappropriately drawn blood cultures (IDBCs) was unchanged, and use in patients with IDBCs was comparable during both periods. Before Intervention 3, 38/55 orders continuing > 72 hours were considered inappropriate versus 24/53 (p < .025) after. After the interventions, hospitalwide vancomycin use was reduced. Yet the overall rate of VRE infection initially decreased but then increased once again over time. DISCUSSION: Despite substantial reduction in hospitalwide vancomycin use, the impact on the overall rate of VRE was inconsistent and ward dependent.