Invasive Aspergillosis

Abstract

Morbidity and mortality caused by invasive Aspergillus infections are increasing. This is because of the higher number of patients with malignancies treated with intensive immunosuppressive therapy regimens as well as their improved survival from formerly fatal bacterial infections, and the rising number of patients undergoing allogeneic haematopoietic stem cell or organ transplantation. Early initiation of effective systemic antifungal treatment is essential for a successful clinical outcome in these patients; however, clinical clues for diagnosis are sparse and early microbiological proof of invasive aspergillosis (IA) is rare. Clinical diagnosis is based on pulmonary CT scan findings and non-culture based diagnostic techniques such as galactomannan or DNA detection in blood or bronchoalveolar lavage samples. Most promising outcomes can be expected in patients at high risk for aspergillosis in whom antifungal treatment has been started pre-emptively, backed up by laboratory and imaging findings. The gold standard of systemic antifungal treatment is voriconazole, which has been proven to be significantly superior to conventional amphotericin B and has led to a profound improvement of survival rates in patients with cerebral aspergillosis. Liposomal amphotericin B at standard dosages appears to be a suitable alternative for primary treatment, while caspofungin, amphotericin B lipid complex or posaconazole have shown partial or complete response in patients who had been refractory to or intolerant of primary antifungal therapy. Combination therapy with two antifungal compounds may be a promising future strategy for first-line treatment. Lung resection helps to prevent fatal haemorrhage in single patients with pulmonary lesions located in close proximity to larger blood vessels, but is primarily considered for reducing the risk of relapse during subsequent periods of severe immunosuppression. Strict reverse isolation appears to reduce the incidence of aspergillosis in allogeneic stem cell transplant recipients and patients with acute myeloid leukaemia undergoing aggressive anticancer therapy. Well designed, prospective randomised studies on infection control measures effective to prevent aspergillosis are lacking. Prophylactic systemic antifungal treatment with posaconazole significantly improves survival and reduces IA in acute myeloid leukaemia patients and reduces aspergillosis incidence rates in patients with intermediate-to-severe graft-versus-host reaction emerging after allogeneic haematopoietic stem cell transplantation. Voriconazole prophylaxis may be suitable for prevention of IA as well; however, the results of large clinical trials are still awaited.

Treatment of invasive fungal infections in cancer patients—Recommendations of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO)

“…The fatality rate is 30-60% [34, 58,72]. Early treatment at first signs of infection is mandatory and can improve the chance of survival (BIII) [11,43].…”

Multicenter Study of Method-Dependent Epidemiological Cutoff Values for Detection of Resistance in Candida spp. and Aspergillus spp. to Amphotericin B and Echinocandins for the Etest Agar Diffusion Method

“…KEYWORDS ECVs, Etest ECVs, Etest MICs Candida, Etest MICs Aspergillus, WT isolates, amphotericin B resistance, antifungal resistance, echinocandin resistance, non-WT, susceptibility marker T he incidence and prevalence of invasive infections caused by Candida, Aspergillus, and other fungal pathogens continue to increase, especially among immunocompromised patients and those with serious underlying diseases; their attributable mortality rates can be as high as 47% depending on the patient population and age (1)(2)(3)(4). Three echinocandins (anidulafungin, caspofungin, and micafungin) have been licensed for intravenous treatment and prevention of invasive Candida infections (including candidemia) (5).…”

In Vitro Analyses of Mild Heat Stress in Combination with Antifungal Agents against Aspergillus fumigatus Biofilm

“…Aspergillus fumigatus is the second most common invasive fungal pathogen after Candida albicans (1). In some patient populations, A. fumigatus is associated with mortality rates ranging from 30% to 90% (2)(3)(4)(5). The significance of biofilm formation in fungal infections caused by Aspergillus spp.…”