Abstract
Invasive aspergillosis has been mainly reported among immunocompromised patients during prolonged periods of neutropenia. Recently, however, non-neutropenic patients in the ICU population have shown an increasing risk profile for aspergillosis. Associations with chronic obstructive pulmonary disease and corticosteroid therapy have been frequently documented in this cohort. Difficulties in achieving a timely diagnosis of aspergillosis in non-neutropenic patients is related to the non-specificity of symptoms and to lower yields with microbiological tests compared to neutropenic patients. Since high mortality rates are typical of invasive aspergillosis in critically ill patients, a high level of suspicion and prompt initiation of adequate antifungal treatment are mandatory. Epidemiology, risk factors, diagnostic algorithms, and different approaches in antifungal therapy for invasive aspergillosis in non-neutropenic patients are reviewed.
Highlights
Invasive aspergillosis (IA) is an opportunistic infection that occurs mainly among patients with hematological malignancies, most notably during prolonged periods of neutropenia, and in subjects with solid tumors, critical illness, and HIV/AIDS, and those undergoing allogeneic stem cell transplantation and solid-organ transplantation [1,2]
We describe the epidemiology of and the risk factors for pulmonary IA in non-neutropenic patients, limitations and advances in the diagnostic process, and the different approaches in antifungal therapy, including the main pharmacological properties of different antifungal drugs
In a retrospective study of 289 IA patients, the authors observed that, after October 2002, the overall survival rate increased from 47.5% to 60.4% (P = 0.01), without concomitant modifications regarding diagnostic strategy [44]
Summary
Invasive aspergillosis (IA) is an opportunistic infection that occurs mainly among patients with hematological malignancies, most notably during prolonged periods of neutropenia, and in subjects with solid tumors, critical illness, and HIV/AIDS, and those undergoing allogeneic stem cell transplantation and solid-organ transplantation [1,2]. Among the various lipidic formulations of amphotericin B, liposomal amphotericin B (LAmB) has the more favorable pharmacokinetic behavior in terms of achieving higher peak plasma levels, having lower intracellular penetration rates and lower clearance through the reticuloendothelial system [104] Both LAmB and amphotericin B lipid complex (ABLC) were shown to achieve therapeutically effective concentrations in the epithelial lining fluid of critically ill patients [105]. Trof and colleagues [11] showed that IA diagnosis was established post-mortem in 38% of patients, 94% of whom did not receive antifungal treatment These data could explain the results observed by Meersseman and colleagues [16] in a restrospective cohort study on 127 ICU patients with IA; patients with proven or probable infection without hematologic malignancy presented a two-fold increase in mortality rate compared with mortality expected by Simplified Acute Physiology Score II score. It is possible that the overall mortality rate from IA is significantly higher in non-neutropenic patients
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