1. ¹Northwestern Memorial Hospital, Chicago, IL, USA
2. ²The Feinberg School of Medicine, Northwestern University, Chicago, IL, USA

Correspondence: Dr J Mehta, Department of Hematology/Oncology, Northwestern University Medical School, 676 N St Clair Street, Suite 850, Chicago, IL 60611-2927, USA. E-mail: j-mehta@northwestern.edu

Received 16 November 2006; Revised 27 March 2007; Accepted 2 May 2007; Published online 25 June 2007.

Abstract

Seventy-one allograft recipients receiving voriconazole, in whom complete clinical, microbiologic and pharmacokinetic data were available, were studied to determine the efficacy of voriconazole in preventing fungal infections. The length of voriconazole therapy was 6–956 days (median 133). The total number of patient-days on voriconazole was 13 805 (38 years). A total of 10 fungal infections were seen in patients on voriconazole (18% actuarial probability at 1 year): Candida glabrata (n=5), Candida krusei (n=1), Cunninghamella (n=1), Rhizopus (n=2) and Mucor (n=1). Two of the four zygomycosis cases were preceded by short durations of voriconazole therapy, but prolonged itraconazole prophylaxis. The plasma steady-state trough voriconazole levels around the time the infection occurred were <0.2, <0.2, 0.33, 0.55, 0.63 and 1.78 g/ml in the six candidiasis cases. Excluding the four zygomycosis cases, all the six candidiasis cases were seen among the 43 patients with voriconazole levels of 2 g/ml and none among the 24 with levels of >2 g/ml (P=0.061). We conclude that voriconazole is effective at preventing aspergillosis. However, breakthrough zygomycosis is seen in a small proportion of patients. The role of therapeutic voriconazole monitoring with dose adjustment to avoid breakthrough infections with fungi that are otherwise susceptible to the drug needs to be explored prospectively.