Abstract
Invasive fungal infections (IFIs) cause significant morbidity, mortality, and increased cost of care in patients with hematological malignancies, prolonged (i.e. >7-10 days) treatment induced neutropenia, and other disease states causing underlying immunosuppression. One strategy often used to combat the development of invasive infections is the use of antifungal agents as prophylaxis in at risk patients. Posaconazole is an oral triazole with a useful spectrum of activity against many fungal pathogens of concern in patients at risk for the development of IFIs. Posaconazole is only available in oral formulation and therapeutic drug monitoring may provide value due to variable absorption and serum concentrations. Clinical efficacy and pharmacoeconomic data have demonstrated the utility of posaconazole in the treatment of oropharyngeal candidiasis and for prophylaxis in patients at risk for development of IFIs. Several organizations or expert groups involved in developing guidelines for the management of IFIs recommend posaconazole anti-fungal prophylaxis in patients with AML or MDS and chemotherapy induced neutropenia or significant GVHD. In addition, nonrandomized studies (largely of salvage therapy) and case series suggest that posaconazole may be effective as treatment for invasive aspergillosis, zygomycosis, and coccidiomycosis. Further, small case series or individual case reports suggest activity against other less commonly encountered filamentous fungi and Histoplasma.
Highlights
Patients who receive allogenieic hematopoietic stem cell transplant (HSCT) are more likely to develop invasive aspergillosis with an incremental cost of treatment estimated in 1998 at $86,635.2,3 Most concerning are the fatality rates associated with these difficult to treat infections which may range as high as 60% to 90% and complicate or delay further chemotherapy, compromising treatment of the underlying malignancy.[4,5]
And colleagues compared posaconazole to itraconazole or fluconazole in 602 patients with neutropenia resulting from chemotherapy for acute myelogenous leukemia or myelodysplastic syndrome.[32]
Invasive fungal infections (IFIs) cause significant morbidity, mortality, and increased cost of care and antifungal prophylaxis is recommended as a means to prevent or reduce these infections in immunocompromised patients
Summary
Invasive fungal infections (IFIs) cause significant morbidity, mortality, and increased cost of care in patients with hematological malignancies, prolonged (i.e. 7–10 days) treatment induced neutropenia, and other disease states or treatments resulting in immunosuppression.[1,2] For example, patients who receive allogenieic hematopoietic stem cell transplant (HSCT) are more likely to develop invasive aspergillosis with an incremental cost of treatment estimated in 1998 at $86,635.2,3 Most concerning are the fatality rates associated with these difficult to treat infections which may range as high as 60% to 90% and complicate or delay further chemotherapy, compromising treatment of the underlying malignancy.[4,5]One strategy often used to combat the development of invasive infections involves the use of antifungal agents as prophylaxis in at risk patients.
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