Objectives: Describe the epidemiology, risk factors and clinical outcomes of invasive aspergillosis (IA) in solid organ transplant recipients (SOTR) in a contemporary cohort. Methods: Using the prospective observational Swiss Transplant Cohort Study (STCS), we retrospectively analyzed all SOTR between 05/2008 and 12/2014 to describe the incidence and clinical outcomes of proven and probable IA (1). To identify risk factors associated with IA, we performed a nested case-control study: patients with IA were identified as index-cases and were matched with controls (1:3 ratio) based on SOT type, time and location of SOT (±6 months of the index case at the same center), and a minimum follow-up similar to that of the index-case. Results: A total of 70/3035 (2.4%) SOTR developed IA. The incidence in heart, kidney, liver, lung, and combined SOT was 7.1%, 1.3%, 1.2%, 8.3%, and 2.6%, respectively. The median time between transplantation and IA was 100 days (interquartile range, IQR: 15-275); shorter in lung (median 11 days; IQR: 5-103) and liver (median 18 days; IQR: 9-122) SOTR. Diagnosis of IA was proven in 29 (41.4%), probable in 41 (55.6%) SOTR, and was based on histopathology (N = 30, 44.1%), culture (N = 68, 97%), and/or serum galactomannan enzyme immunoassay (N = 15, 21%). Using the nested case-control data, prior infections with bacteria (odds ratio, OR: 4.6, 95% confidence interval, CI: 2.23, 9.57, P < .001), respiratory viruses (OR: 11.1, 95%CI: 3.06, 40.15, P < .001), CMV (OR: 2.91, 95%CI: 1.3, 6.54, P = .01), and fungal pathogens (OR: 2.6, 95%CI: 1.10, 6.11, P = .0.3) were identified as significant predictors of IA. Moreover, intravenous administration of glucocorticosteroids (OR: 5.4, 95%CI: 1.45, 20.14, P = .01) and renal failure (OR: 4.3, 95%CI: 1.64, 11.17, P = .003) were also identified as risk factors for IA. Sixteen of 70 (22.9%) patients with IA were dead by 12 weeks: 4 in 15 heart (26.7%), 5 in 20 kidney (25%), 6 in 7 liver (85.7%), and 1 in 24 lung (4.2%) transplant recipients, respectively (P < .001). Univariate analyses identified liver transplantation as a risk factor for 12-weekmortality (HR 33.7; 95%CI 4.01-283.51), followed by bacterial co-infection (HR: 2.74; 95% CI 1.02-7.37), CMV infection (HR 3.36; 95% CI 1.25-9.05), extra-pulmonary IA (HR 2.94; 95%CI 1.09-7.72) and a treated rejection event (HR 2.94; 95% CI 1.10-7.86). Conclusion: IA remains an important infection among SOTR, affecting primarily heart and lung SOTR. Co-infections with other pathogens (mainly bacterial and viral) appear to increase susceptibility to IA and 12-week survival. Mortality remains high among liver SOTR with IA. References: 1. De Pauw, B., et al., Revised definitions of invasive fungal disease from the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) Consensus Group. Clin Infect Dis, 2008. 46(12): p. 1813-21.
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- TIMM 8th (2017)