Echinocandins - first line in invasive candidiasis: how strong is this 'strong' evidence?

Abstract

In the previous issue of Critical Care, Kett and colleagues [1] published a post hoc analysis of a randomized controlled trial comparing the effi cacy of anidulafungin versus fl uconazole in non-neutropenic critically ill patients with invasive Candida infections (89% had candidemia). But the authors’ claim that their data support the superiority of anidula fungin may be misleading and raises several concerns. First, the primary endpoint of the study was clinical and microbiological success at the end of intravenous therapy. However, surrogate endpoints must be predictive of the clinically relevant endpoint that is mortality [2]. Th at was not the case, and no diff erence in 28-day mortality was noted (20.2% versus 24.3%; P = 0.57). Second, in the present study [1], the duration of intra venous therapy was unclear, but in their original study [3], patients on anidulafungin received, on average, 3 more days of intravenous therapy than the fl uconazol group. Besides, more patients in the anidulafungin arm had their central venous catheter removed. Th ese facts markedly biased the results and could explain the observed diff erences [4]. Th ird, this was a non-inferiority study [3]. Th erefore, from a statis tical point of view, any conclusions regarding superiority must be interpreted with extreme caution [5]. Finally, at the time of the study design [3], the use of amphotericin B, and not fl uconazole, was recommended in unstable patients with invasive Candida infections. Th erefore, the choice of fl uconazole as a comparator limits the study conclusions even further. We believe that, at present, there is no evidence to support the selection of a specifi c antifungal class in invasive Candida infections [4].