Significant alterations in the epidemiology and treatment outcome of invasive fungal infections in patients with hematological malignancies

Department of Internal Medicine, Division of Hematology and Oncology, Innsbruck Medical University, Innsbruck, Austria.
International journal of hematology (Impact Factor: 1.92). 12/2008; 88(5):508-15. DOI: 10.1007/s12185-008-0184-2
Source: PubMed


Invasive fungal infections (IFI) remain a leading cause of morbidity and mortality in immunocompromised patients. This retrospective single-center study analyzed incidence, treatment and outcome of invasive fungal infections in 1,095 patients with hematological malignancies receiving either cytoreductive chemotherapy or autologous or allogeneic hematopoietic stem cell transplantation at our institution between 1995 and 2004. IFI occurred in 167/1,095 (15%) patients with a significant increase over time (12.7% between 1995 and 2000 vs. 18.1% in the later IFI cohort, P = 0.0134). Fifty-four (32%) patients had proven, 70 (42%) patients had probable, and 43 (26%) patients suffered from possible IFI according to EORTC/MSG criteria. In 108/124 (87%) cases with proven or probable IFI, moulds were the causative pathogens. Both, Aspergillus fumigatus (n = 46) and Aspergillus
terreus (n = 41) were predominant. Yeast infections (Candida spp.) were documented in 16/124 (10%) cases with proven or probable IFI. Median overall survival of the entire IFI cohort was 7 (3–17) months. Overall survival was significantly better in patients with probable or possible IFI (37 and 38%, respectively) compared with patients with proven IFI (28%, P = 0.019). In 35% of patients, IFI was the principal cause of death with a significant decrease over time (44% in time cohort 1995–2000 vs. 28% in the later IFI cohort, P = 0.018) accompanied by an increased use of novel antifungals. By multivariate analysis, only proven IFI was significantly predictive for death (HR 1.7, P = 0.018). A significant decrease in fungus-related deaths was observed despite a significant increase of IFI over time, probably due to improved diagnostic and therapeutic approaches.

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    • "However, these studies pre-date the availability improved diagnostics and newer antifungal agents studied in our analysis. Our study may reflect a recent trend of decreasing mortality in patients with aspergillosis [11,21,22]. Kim and colleagues describe crude in-hospital mortality of 36.7% reported for years 2005–2006 in a broad national cohort of hospitalized patients with IA [11]. "
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    ABSTRACT: Background Few data are available regarding the epidemiology of invasive aspergillosis (IA) in ICU patients. The aim of this study was to examine epidemiology and economic outcomes (length of stay, hospital costs) among ICU patients with IA who lack traditional risk factors for IA, such as cancer, transplants, neutropenia or HIV infection. Methods Retrospective cohort study using Premier Inc. Perspective™ US administrative hospital database (2005–2008). Adults with ICU stays and aspergillosis (ICD-9 117.3 plus 484.6) who received initial antifungal therapy (AF) in the ICU were included. Patients with traditional risk factors (cancer, transplant, neutropenia, HIV/AIDS) were excluded. The relationship of antifungal therapy and co-morbidities to economic outcomes were examined using Generalized linear models. Results From 6,424 aspergillosis patients in the database, 412 (6.4%) ICU patients with IA were identified. Mean age was 63.9 years and 53% were male. Frequent co-morbidities included steroid use (77%), acute respiratory failure (76%) and acute renal failure (41%). In-hospital mortality was 46%. The most frequently used AF was voriconazole (71% received at least once). Mean length of stay (LOS) was 26.9 days and mean total hospital cost was $76,235. Each 1 day lag before initiating AF therapy was associated with 1.28 days longer hospital stay and 3.5% increase in costs (p < 0.0001 for both). Conclusions Invasive aspergillosis in ICU patients is associated with high mortality and hospital costs. Antifungal timing impacts economic outcomes. These findings underscore the importance of timely diagnosis, appropriate treatment, and consideration of Aspergillus as a potential etiology in ICU patients.
    Full-text · Article · Jan 2013 · BMC Infectious Diseases
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    • "In immunocompromised and especially in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) invasive aspergillosis (IA) remains a main obstacle to overcome during hospitalisation. e overall incidence of IA in patients with hematological malignancies varies between 0.3% and 15%, depending on the underlying disease [1] [2] [3] [4] [5] [6] [7]. Case fatality rates up to 87% are reported for patients following allogeneic HSCT [12]. "
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    ABSTRACT: Invasive fungal infections (IFI) remain a leading cause of morbidity and mortality in immunocompromised patients. Despite major improvements, it often remains difficult to obtain accurate diagnosis in neutropenic patients. Timely initiation of antifungal treatment in this high-risk population is mandatory to improve survival. Today, clinicians have a choice among a growing armamentarium of novel antifungal agents. Agents such as "veteran" amphotericin B deoxycholate (d-AMB) have been replaced with lipid formulations, and new generation triazoles as well as novel class echinocandins finally offer opportunities to improve prognosis with less systemic toxicity. Clinical decision-making depends on several guidelines, published studies and not least on economic considerations. The current review summarises up-to-date treatment recommendations of the DGHO/AGIHO, and ECIL-3, as well as the recently published 2010 Clinical Practice Guidelines of the IDSA.
    Full-text · Article · Dec 2012 · memo - Magazine of European Medical Oncology
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    • "Interestingly, in this heterogeneous population, the authors also found that the degree of certainty of diagnosis is an independent prognostic factor, with an improved OS in patients with possible aspergillosis. In contrast, in the study by Auberger et al.,7 whose analysis was similar to ours, only proven IFI was predictive for death in a multivariate analysis. A possible reason why they could not identify more risk factors might be the inhomogeneous population analysed, including patients with intensive chemotherapy, and autologous and allogeneic SCT. "
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    ABSTRACT: Invasive fungal infections (IFIs) contribute significantly to mortality and morbidity in patients receiving myelosuppressive chemotherapy for haematological malignancies. The present study investigates the overall survival (OS), infection-related mortality and changes in treatment of IFIs in our department from 1995 until 2006. Outcomes of all chemotherapy courses were retrospectively evaluated using a standard questionnaire. Modified EORTC/MSG criteria for IFIs were applied: a positive PCR result for Aspergillus spp. in bronchoalveolar lavage was also defined as probable IFI. In total, 1693 chemotherapy courses in 592 patients were evaluated. Sixty-three percent of chemotherapy courses were given to treat acute myeloid leukaemia, with the rest for acute lymphoblastic leukaemia or aggressive lymphoma. IFIs were observed in 139/592 patients [23.5%, 95% confidence interval (CI) 20%-27%] and in 149/1693 courses (8.8%, 95% CI 8%-10%). IFI-related mortality was 56.9% in 1995-2001 and 28.6% in 2002-06, P < 0.001. Accordingly, median OS in patients with IFI increased: 54 days (95% CI 26-82 days) in 1995-2001 versus 229 days (95% CI 35-423 days) in 2002-06, P = 0.001. By multivariate analysis, factors predictive for better OS were controlled disease after chemotherapy [hazard ratio (HR) 0.228, P < 0.001], possible IFI (in contrast to proven/probable IFI, HR 0.537, P = 0.005), age <60 years (HR 0.583, P = 0.008), time period 2002-06 (HR 0.612, P = 0.021) and use of novel antifungals (HR 0.589, P = 0.033). Compared with 1995-2001, IFI-related mortality decreased and OS in patients with IFI increased significantly in recent years. Improved OS was associated with controlled haematological disease, certainty of IFI diagnosis (possible), younger age, time period 2002-06 and the use of novel antifungals.
    Full-text · Article · Apr 2010 · Journal of Antimicrobial Chemotherapy
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