Antifungal Prophylaxis: Anything New?
Profound immunosuppression is one of the major risk factors for development of invasive fungal infections (IFI). Patients with hematologic malignancies and those undergoing bone marrow transplantation are at high risk of these infections.
IFI are frequently associated with high mortality rates. The meta-analysis of the antifungal prophylaxis trials suggests that prophylactic use of antifungal agents such as
fluconazole or
itraconazole is efficacious in decreasing the incidence of IFI as well as the mortality attributable to IFI, particularly in bone marrow transplant recipients and for infections due to yeasts. Based on these data, recommendations documented in "European Conference on Infections in Leukemia (ECIL)" include the prophylactic use of fluconazole (strongly recommended) and itraconazole (generally recommended) in allogeneic transplant recipients.
Due primarily to the availability of novel antifungal agents, clinical trials are now being carried out to compare the prophylactic potency of the new drugs with that of those already in use. A drug that has been investigated in this respect is the novel echinocandin,
micafungin. The use of micafungin for prophylaxis against
Candida infections in hematopoietic stem cell transplant (HSCT) recipients during neutropenia and pre-engraftment period has already been approved by FDA in 2005. The other antifungal that has been studied more recently is the novel triazole, posaconazole.
Posaconazole (Noxafil) is active in vitro against a variety of fungi, including
Candida,
Aspergillus, class
Zygomycetes, some
Fusarium isolates,
Scedosporium apiospermum, thermally dimorphic fungi and some dematiaceous fungal genera. Importantly, its activity covers some
Candida spp. (such as some of the isolates belonging to
C. krusei and
C. glabrata) that are less susceptible to fluconazole. Also, its activity against fungi from the class Zygomycetes is of remarkable significance. Posaconazole is available only as oral suspension formulation.
The first approval for clinical use of posaconazole was salvage therapy. The use of posaconazole in treatment of adult patients with invasive aspergillosis, fusariosis, mycetoma, chromoblastomycosis, and coccidioidomycosis who remain refractory or intolerant to other antifungal agents was approved by the European Commission.
As of September 18, 2006, FDA has approved the use of posaconazole for prophylaxis of IFI as well, for specific settings. These include (i) patients who receive remission-induction chemotherapy for acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS), and are expected to experience prolonged neutropenia, and (ii) HSCT recipients who are undergoing high-dose immunosuppressive therapy for graft-versus-host disease. These indications were based on the results of the clinical trials, which proved enhanced efficacy and improved overall survival with prophylactic posaconazole as compared to those with fluconazole or itraconazole.
Novel drugs have added more to the antifungal prophylaxis armamentarium as well. Precise definition of patients who are at greatest risk of IFI and who require antifungal prophylaxis remains as the critical point in rational prophylactic use of antifungal drugs.
Related reading
-
Cornely OA et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med. 2007; 356: 348-59.
-
Maertens J. Evaluating prophylaxis of invasive fungal infections in patients with haematologic malignancies. Eur J Haematol. 2007 Jan 23; [Epub ahead of print].
-
Paugam A. The latest data on posaconazole. Med Mal Infect. 2007 Jan 29; [Epub ahead of print].
-
Ullman AJ et al. Posaconazole or fluconazole for prophylaxis in severe graft-versus-host disease. N Engl J Med. 2007; 356: 335-47.
-
Van Burik JA. Role of new antifungal agents in prophylaxis of mycoses in high risk patients. Curr Opin Infect Dis. 2005; 18:479-83.
