Although prophylactic use of fluconazole is safe and effective in preventing invasive candidiasis, this strategy is ineffective against invasive aspergillosis. Many transplant centers have instituted prophylactic strategies utilizing agents with activity against Aspergillus species such as itraconazole secondary to the high morbidity and mortality rates associated with invasive aspergillosis in high-risk immunocompromised patients. In a
prospective, open-label multi-center trial of antifungal prophylaxis in allogeneic hematopoietic stem cell transplants recipients itraconazole did reduce the number of invasive fungal infections compared to fluconazole (9% vs. 25%, respectively; Fig. 2B) (60). A second open-label study conducted at a single-center reported significantly more proven and probable invasive fungal infections in patients randomized to fluconazole versus itraconazole (61). This difference was due to increases in the number of invasive mould infections (primarily aspergillosis). Interestingly, this study was amended after 197 patients were enrolled due to concerns with the safety of itraconazole when administered with cyclophosphamide during the conditioning regimen. Increases in serum bilirubin and a doubling of serum creatinine were observed in patients due a previously unrecognized drug interaction between these two agents when administered concurrently (62). Following this interim analysis, the protocol was changed to start prophylaxis the day of stem cell transplant after completion of the conditioning regimen. In addition, in both studies a significant portion (24-36%) of patients experienced gastrointestinal adverse effects, which resulted in approximately one quarter of the patients discontinuing prophylaxis with itraconazole in one study (61).
Continue reading here: Posaconazole Prophylaxis
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