Review of Newer Antifungal and Immunomodulatory Strategies for Invasive Aspergillosis

Abstract

The incidence of invasive aspergillosis is markedly increasing, and mortality remains dismal. Previously there were only 2 antifungals with activity against Aspergillus, but over the last few years there has been an explosion of newer agents and reformulations of older antifungals. Exploration has also begun with immunotherapy, with use of cytokines and granulocyte transfusions alone or in combination with antifungal therapy. This review will detail the available in vitro, in vivo, and clinical experience with the newer antifungal and immunomodulatory therapies in development for treatment of invasive aspergillosis.

Immunosuppression Related to Collagen-Vascular Disease or Its Treatment

“…It causes pulmonary, central nervous system, and disseminated disease in those who are immunocompromised. Voriconazole, a triazole similar to fluconazole and itraconazole, is now considered the drug of choice for invasive aspergillosis, replacing amphotericin B deoxycholate, a toxic and poorly tolerated drug (30). Voriconazole can be administered intravenously or orally, with 90% or greater bioavailability and good penetration into brain tissue and the meninges.…”

Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients

“…During the past decade, other pathogens such as A. terreus, due in part to its innate 21,22 Ubiquitous fungal species previously considered as colonizers or contaminants including Trichosporon, Fusarium, and Scedosporium have also been observed as invasive pathogens with increasing frequency in HSCT recipients (Table 4). …”

“…In patients with refractory/intolerant of other antifungals, Pos was effective against 53% of aspergillosis, 75% of invasive candidiasis, and 75% of fusariosis 22,84 Oral formulation only. 124 neutropenic patients were randomized between caspofungin 50 mg/day vs Itra 200 mg/day, at a median of 23 days on the study, both drugs provided comparable antifungal prophylaxis and were well tolerated 58 Caspofungin was equivalent to AmB as a primary treatment of patients with invasive candidiasis and candidemia 86 Interaction: CY m blood-level of caspofungin by 35%, and may induce liver toxicity, in absence of further data such combination is not recommended.…”

“…56 In a multicenter study in which 25 patients with refractory IFIs or who were intolerant to standard therapy, posaconazole was well tolerated and effective in 53% of patients at week 4, and 85% of patients by week 8. 22 The new triazoles are attractive alternatives for antifungal prophylaxis as all have enhanced potency, a broadspectrum of activity and are available in oral formulation.…”

Detection of Aspergillus fumigatus and a Mutation That Confers Reduced Susceptibility to Itraconazole and Posaconazole by Real-Time PCR and Pyrosequencing

“…Unfortunately, conventional laboratory tests, such as culture and galactomannan detection, lack sensitivity and are rarely conclusive, resulting in true-positive results only at advanced stages of infection or necessitating invasive procedures for formal microbiological evaluation (2,5). Furthermore, the emergence of clinical resistance to commonly used azole drugs impedes successful treatment (3,8,12). Therefore, the development of techniques to facilitate the early and reliable diagnosis of invasive aspergillosis and to predict susceptibility to antifungal drug treatment is currently under active investigation.…”