Preventing invasive fungal infections: Results of two studies on posaconazole

April 1, 2007

Invasive fungal infections continue to be a major cause of morbidity and mortality in immunosuppressed patients. Two studies recently addressed the effectiveness of the newer antifungal posaconazole in the prevention of these infections. The first study compared posaconazole with fluconazole in patients with graft versus host disease. The second compared it with fluconazole or itraconazole in patients with prolonged neutropenia.

Invasive fungal infections continue to be a major cause of morbidity and mortality in immunosuppressed patients. Two studies recently addressed the effectiveness of the newer antifungal posaconazole in the prevention of these infections. The first study compared posaconazole with fluconazole in patients with graft versus host disease. The second compared it with fluconazole or itraconazole in patients with prolonged neutropenia.

Ullmann and colleagues: Their study included 600 recipients of hematopoietic stem cell transplants who had severe graft versus host disease and were receiving immunosuppressive therapy. The patients were randomly assigned to receive oral posaconazole or fluconazole as prophylaxis against invasive fungal infections.

After 112 days, posaconazole was documented to be as effective as fluconazole in the prevention of all invasive fungal infections and was better than fluconazole in the prevention of proven or probable invasive aspergillosis (Table). Breakthrough fungal infections were less likely to occur in patients who were receiving posaconazole than in those receiving fluconazole (all fungal infections, 2.4% vs 7.6%, P = .004; invasive aspergillosis, 1% vs 5.9%, P = .001).

The number of deaths from invasive fungal infections was lower in the posaconazole group than in the fluconazole group (1% vs 4%, P = .046). The 2 groups did not differ with respect to overall mortality. The groups also did not differ in the incidence of treatment-related adverse events.

Cornely and colleagues: Their study included patients who were undergoing chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome; all had prolonged neutropenia. The patients were randomly assigned to receive oral antifungal prophylaxis with posaconazole (304) or either fluconazole (240) or itraconazole (58).

The study found that proven or probable invasive fungal infections were significantly less likely to occur in patients who received posaconazole (2%) than in those who received fluconazole or itraconazole (8%). In addition, mortality from any cause was significantly lower in the posaconazole group than in the fluconazole or itraconazole group (16% vs 22%, P = .048).

The most common adverse events in both groups were GI disturbances. Adverse events were significantly more likely to occur in the posaconazole group (6%) than in the fluconazole or itraconazole group (2%).

Based on these findings, the authors conclude that posaconazole is more effective than fluconazole or itraconazole in preventing invasive fungal infections in patients who are undergoing chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome.