Voriconazole versus Amphotericin B for Invasive Aspergillosis

Abstract

Herbrecht et al. (Aug. 8 issue)¹ show the superiority of voriconazole over amphotericin B for primary therapy of invasive aspergillosis. However, we are concerned about the striking difference in the duration of treatment: a median of 10 days with amphotericin B, as compared with 77 days with voriconazole. How can one be so sure that “the superiority of voriconazole . . . was not the result of excessive interruptions” of amphotericin B? First, the use of one of the lipid formulations of amphotericin B, which are tolerated better by the kidneys than amphotericin B deoxycholate,² would probably have reduced the number of discontinuations in the control group. Second, an alternative antifungal agent was given to 107 patients in the amphotericin B group and to 52 patients in the voriconazole group. Because severe adverse events accounted for 45 discontinuations in the amphotericin B group and for 26 discontinuations in the voriconazole group, we wonder whether the other interruptions were explained by a poor response to initial therapy (which may be problematic in an open-label study). Therapy was switched from amphotericin B to itraconazole, the efficacy of which remains debatable in this setting, in 38 patients and from voriconazole to itraconazole in only 17 patients. This difference may partly account for the worse results in the amphotericin B group. The excess mortality in the amphotericin B group was evident after about 10 days, which coincides with the median duration of amphotericin B treatment.