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 (B38 years). A total of 10 fungal infections were seen in patients on voriconazole (18% actuarial probability at 1 year): Candida glabrataand Mucor (n ¼ 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 o0.2, o0.2, 0.33, 0.55, 0.63 and 1.78 lg/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 p2 lg/ml and none among the 24 with levels of 42 lg/ml (P ¼ 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.

Pulmonary aspergillosis in hematologic malignancies: lights and shadows

“…[31][32][33][34][35][36][37] However, it is still to be decided which is the best choice of treatment. Posaconazole seems to be better when compared to others, since not only is it active in vitro against a wide range of yeasts (including candida species) and molds (including aspergillus species, zygomycetes, and fusarium species) but also appears to have an acceptable adverse-event profile and it is well tolerated.…”

Development and application of two independent real-time PCR assays to detect clinically relevant Mucorales species

“…Breakthrough invasive mucormycosis has been observed in patients receiving voriconazole or echinocandins (Kontoyiannis et al, 2005;Trifilio et al, 2007), and also for posaconazole (Kang et al, 2015;Mousset et al, 2010), showing reduced sensitivity of some Mucorales species (Almyroudis et al, 2007).…”

Tacrolimus use in adult allogeneic stem cell transplant recipients receiving voriconazole: preemptive dose modification and therapeutic drug monitoring

“…Voriconazole is a triazole drug with a broad spectrum of activity, and is one of the agents used for fungal prophylaxis after allogeneic HSCT. 7,8 Voriconazole is a competitive inhibitor for the cytochrome P450 3A4, 2C9 and 2C19 isosenzyme systems. 9,10 Predictably, numerous serious drug interactions have been described for voriconazole when combined with other drugs metabolized through these systems, including tacrolimus.…”