Review of Newer Antifungal and Immunomodulatory Strategies for Invasive Aspergillosis

Steinbach, William J.; Stevens, David A.

doi:10.1086/376523

Cited by 149 publications

(110 citation statements)

References 339 publications

(433 reference statements)

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“…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.…”

Section: Aspergillus Speciesmentioning

confidence: 99%

Immunosuppression Related to Collagen-Vascular Disease or Its Treatment

Hamilton¹

2005

Proceedings of the American Thoracic Society

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Collagen-vascular diseases are associated with immune dysregulation and inflammation, leading to tissue destruction or compromise. Immunosuppression is more commonly associated with the drugs used to treat these disorders than with the diseases themselves. The newest agents being used to treat collagen-vascular diseases are the tumor necrosis factor (TNF)-␣ inhibitors. U.S. Food and Drug Administration-approved TNF-␣ inhibitors have differing effects on the immune system, reflecting their potency and mechanisms of action. They are particularly effective in breaking down granulomatous inflammation, which makes them effective treatment for sarcoidosis and Wegener's granulomatosis. This same property makes them likely to break down the host defense mechanism that normally contains pathogens such as mycobacteria and fungi in a dormant state, namely the physical and immunologic barrier formed by granulomas in the lung and elsewhere. The most common infection reported with the TNF-␣ inhibitors has been tuberculosis, which may manifest as pulmonary and/or extrapulmonary disease, with the latter being more common and severe than usual. Histoplasma capsulatum, Aspergillus, Cryptococcus neoformans, and Listeria monocytogenes have also been described in a number of cases, and their frequency is discussed.

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Section: Aspergillus Speciesmentioning

confidence: 99%

Immunosuppression Related to Collagen-Vascular Disease or Its Treatment

Hamilton¹

2005

Proceedings of the American Thoracic Society

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“…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). …”

Section: Emerging Fungal Pathogensmentioning

confidence: 99%

“…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.…”

Section: Posaconazolementioning

confidence: 99%

“…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.…”

Section: Posaconazolementioning

confidence: 99%

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Choices aplenty: antifungal prophylaxis in hematopoietic stem cell transplant recipients

Hamza

Ghannoum

Lazarus

2004

Bone Marrow Transplant

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Summary:The incidence of invasive fungal infection (IFIs) in hematopoietic stem cell transplantation (HSCT) recipients ranges from 10 to 25% with an overall case fatality rate of up to 70-90%. Candida and Aspergillus genera remain the two most common pathogens. Although fluconazole prophylaxis in this population has been moderately effective in reducing mortality due to invasive candidiasis, this agent does not have activity against invasive aspergillosis (IA) and other mould. Several new agents such as voriconazole and caspofungin have enhanced potency and broad-spectrum antifungal activity and show promising results against yeasts and filamentous fungi when given as therapy and as chemoprophylaxis. Further, new diagnostic tools to detect circulating fungal antigens in biological fluids and PCR-based methods to detect species or genus-specific DNA or RNA have been developed. Incorporating these techniques along with clinical criteria appear to improve the accuracy of preclinical diagnosis of IFIs. Such approaches may alter the current treatment strategy from prophylaxis to preemptive therapy, thereby potentially decreasing cost and toxicity in high-risk patients.

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“…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.…”

mentioning

confidence: 99%