The difference was not significant, as was the difference of the success rates in the composite primary endpoint (36% vs. 38%) made up of defervescence and absence of emergent fungal infection, discontinuation of study drug for toxicity or use of other systemic antifungals. At a first glance, these results may be interpreted as evidence that antifungal therapy is dispensable or ineffective in ICU patients with signs of systemic infection.
Yet, the efficacy of antifungals in documented candidaemia has been established in large prospective trials. We therefore Dabrafenib conclude that the criteria used for the identification of patients at high risk of IC in this study were not adequate and too broad to select for the relevant patient population. Recently updated guidelines from three international expert boards provide rather concise guidance on the choice of suitable antifungal agents for the initial therapy of invasive Candida infections. Treatment recommendations are mostly focussed on bloodstream infection, which is the most common manifestation of IC in intensive care patients. According to the 2009 guidelines of the Infectious Disease Society of America (IDSA),42 an echinocandin is the treatment of choice for candidaemia in moderately to severely ill patients with or without neutropenia and in all patients with previous exposure to azole antifungals. Fluconazole may be used
in less critically ill patients. To date, the term ‘moderately to severely ill’ has not been defined more precisely by the IDSA experts. In our view, intensive care patients generally must be allocated Selleckchem Olaparib to this high-risk category because of failure or major insufficiency of one or more organs and/or haemodynamic instability. The
European Conference on Infections in Leukemia (ECIL-3)43 confirms the notion of echinocandins being the first-choice option with grade A–I recommendations, particularly if therapy is initiated prior to species identification. Voriconazole is recommended with grade A–I in patients without previous azole prophylaxis. According to ECIL, liposomal amphotericin B is an equivalent alternative – which may appear less attractive because of a 30% rate of renal function deteriorations44 and excessive cost. Guanylate cyclase 2C The initial use of fluconazole is restricted to less severely ill patients without azole pre-exposure. Use of azoles is discouraged in C. glabrata infections. In the 2009 update of their guidelines on treatment of fungal infections in cancer patients, the German Society of Hematology and Oncology Infectious Diseases Working Group (DGHO-AGIHO)45 recommends the use of an echinocandin for the initial therapy of IC (grade A–I). Based on the randomised trial showing the inferiority of fluconazole in contrast to anidulafungin in non-neutropenic patients46 and the prevalence of Candida strains with reduced fluconazole susceptibility, the AGIHO explicitly recommends preference of an echinocandin as the primary treatment.