title: Breakthrough fungal infections after allogeneic hematopoietic stem cell transplantation in patients on prophylactic voriconazole.
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 ( 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.
authors.affiliation: Northwestern Memorial Hospital, Chicago, IL, USA.
authors.forename: S
authors.initials: S
authors.lastname: Trifilio
authors.forename: S
authors.initials: S
authors.lastname: Singhal
authors.forename: S
authors.initials: S
authors.lastname: Williams
authors.forename: O
authors.initials: O
authors.lastname: Frankfurt
authors.forename: L
authors.initials: L
authors.lastname: Gordon
authors.forename: A
authors.initials: A
authors.lastname: Evens
authors.forename: J
authors.initials: J
authors.lastname: Winter
authors.forename: M
authors.initials: M
authors.lastname: Tallman
authors.forename: J
authors.initials: J
authors.lastname: Pi
authors.forename: J
authors.initials: J
authors.lastname: Mehta
mesh_terms: D000935:Antifungal Agents / Q000627:therapeutic use; D001228:Aspergillosis / Q000188:drug therapy / Q000517:prevention & control; D002177:Candidiasis / Q000188:drug therapy; D003625:Data Collection; D004341:Drug Evaluation; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D009181:Mycoses / Q000188:drug therapy*; D011292:Premedication; D011743:Pyrimidines / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D014230:Triazoles / Q000097:blood / Q000493:pharmacokinetics / Q000627:therapeutic use*; D065819:Voriconazole; D020096:Zygomycosis / Q000188:drug therapy
chemical_list: D000935:Antifungal Agents; D011743:Pyrimidines; D014230:Triazoles; D065819:Voriconazole