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

Excerpt

In the previous issue of Critical Care, Kett and colleagues [1] published a post hoc analysis of a randomized controlled trial comparing the efficacy of anidulafungin versus fluconazole in non-neutropenic critically ill patients with invasive Candida infections (89% had candidemia). But the authors' claim that their data support the superiority of anidulafungin 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]. That was not the case, and no difference in 28-day mortality was noted (20.2% versus 24.3%; P = 0.57). Second, in the present study [1], the duration of intravenous therapy was unclear, but in their original study [3], patients on anidulafungin received, on average, 3 more days of intravenous therapy than the fluconazol group. Besides, more patients in the anidulafungin arm had their central venous catheter removed. These facts markedly biased the results and could explain the observed differences [4]. Third, this was a non-inferiority study [3]. Therefore, from a statistical 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 fluconazole, was recommended in unstable patients with invasive Candida infections. Therefore, the choice of fluconazole as a comparator limits the study conclusions even further. We believe that, at present, there is no evidence to support the selection of a specific antifungal class in invasive Candida infections [4]. …