Early this year the IDSA published new, modified guidelines providing recommendations on the management of patients with Candidiasis (Full Text Here). Of particular focus, and one of the primary changes implemented in these updated guidelines, is the recommendation that all patients with Candida fungemia be initially treated with an echinocandin up front rather than fluconazole, regardless of their immune status.
The basis for this recommendation is based on a number of studies that suggested that for invasive Candidiasis, echinocandin therapy appeared to produce equivalent and perhaps more favorable outcomes when compared to fluconazole therapy (see references below). One of the primary papers to help establish this trend comes from Reboli and colleagues from NEJM, who in 2007 performed a double-blinded non-inferiority study comparing anidulafungin to fluconazole for the treatment of Candida fungemia. A minimum of 14 days of antifungal therapy (either with anidulafungin or fluconazole) was provided to all patients once fungemia was confirmed to be cleared, and treatment success was defined as achieving both symptom resolution along with microbiological clearance of fungemia. Both the anidulafungin and fluconazole study arms displayed no statistically significant differences in demographic factors, risk factors or the incidence of the different Candida species found in the blood at the time of diagnosis. At end of therapy, 2-, and 6-weeks after, those on anidulafungin appeared to be better than those on fluconazole therapy with respect to the primary endpoint [statistically significant up to the 2 week follow up point]. Given these findings, anidulafungin was deemed to be non-inferior to fluconazole in the empiric treatment of Candida associated fungemia.
Studies like the one above are further reinforced by the increasing rates of fluconazole resistant Candida species noted in our health care settings. In Reboli’s study, the primary Candida species noted in the blood were C. albicans and C. glabrata, of which the latter species has variable susceptibility to fluconazole. Other Candida species, such as C. kruzeii, are intrinsically resistant to fluconazole, and the incidence of this organism is increasing in the hospital setting. In addition, the side effect profile of echinocandins when compared to azole agents are more favorable, with less potential hepatotoxicity and drug-drug interactions associated with the echinocandins when compared to drugs like fluconazole.
Thus, given the above points, the recommendation now is for empiric echinocandin therapy for patients who develop Candida fungemia, with plans for step-down to oral therapy if possible in 5-7 days, after species and susceptibility data are available. The new recommendation for obtaining the species and susceptibility data on Candida found in the blood also underline the increasing incidence of fluconazole resistant strains in the nosocomial setting. Newer oral drugs, such as voriconazole, posaconazole and the new extended spectrum isavuconazole, appear to show promise as alternatives for fluconazole in providing oral therapy for Candida fungemia, but further studies will need to be done before these drugs are more definitively cemented into the guidelines.
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