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 ( approximately 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 microg/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 < or =2 microg/ml and none among the 24 with levels of >2 microg/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.