Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes

Purpose:To describe concisely the current standards of care, major recent advances, common beliefs that have been contradicted by recent trials, areas of uncertainty, and clinical studies that need to be performed over the next decade and their expected outcomes with regard to Candida and Aspergillus infections in non-neutropenic patients in the ICU setting. Methods:A systematic review of the medical literature taking account of national and international guidelines and expert opinion. Results:Severe invasive fungal infections (IFIs) are becoming increasingly frequent in critically ill patients. Approximately 80% of IFIs are due to Candida spp. and 0.3-19% to Aspergillus spp. Recent observations emphasize the necessity of building a worldwide sentinel network to monitor the emergence of new fungal species and changes in susceptibility. Robust data on the attributable mortality are essential for the design of clinical studies with mortality endpoints. Although early antifungal therapy for Candida has been recommended in patients with risk factors, sepsis of unknown cause, and positive Candida serum biomarkers [β-1 → 3-d-glucan (BDG) and Candida albicans germ tube antibody (CAGTA)], its usefulness and influence on outcome need to be confirmed. Future studies may specifically address the optimal diagnostic and therapeutic strategies for patients with abdominal candidiasis. Better knowledge of the pharmacokinetics of antifungal molecules and tissue penetration is a key issue for intensivists. Regarding invasive aspergillosis, further investigation is needed to determine its incidence in the ICU, its relationship with influenza outbreaks, the clinical impact of rapid diagnosis, and the significance of combination treatment. Conclusions:Fundamental questions regarding IFI have to be addressed over the next decade. The clinical studies described in this research agenda should provide a template and set priorities for the clinical investigations that need to be performed.

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“…[26]. The "classical" risk factors for IPA are classified in high, intermediate, and low risk categories (Table 2).…”

Section: Invasive Aspergillosismentioning

confidence: 99%

“…According to Taccone et al, the mortality predictors for critically ill with IPA include age, SOFA score, mechanical ventilation, and renal replacement therapy at diagnosis [26,88].…”

Section: Invasive Aspergillosismentioning

confidence: 99%

Intensive care medicine research agenda on invasive fungal infection in critically ill patients

et al. 2017

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“…Af has also been implicated in the pathogenesis of asthma, chronic obstructive airways disease, and bronchiectasis (11)(12)(13). Treatment options remain limited, and high mortality rates persist (14). Better understanding of susceptibility to PA in the nonneutropenic host is a key clinical research priority.…”

mentioning

confidence: 99%

Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death

Shah

Kannambath

Herbst

et al. 2016

Am J Respir Crit Care Med

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Rationale: Pulmonary aspergillosis is a lethal mold infection in the immunocompromised host. Understanding initial control of infection and how this is altered in the immunocompromised host are key goals for comprehension of the pathogenesis of pulmonary aspergillosis.Objectives: To characterize the outcome of human macrophage infection with Aspergillus fumigatus and how this is altered in transplant recipients on calcineurin inhibitor immunosuppressants. Methods:We defined the outcome of human macrophage infection with A. fumigatus, as well as the impact of calcineurin inhibitors, through a combination of single-cell fluorescence imaging, transcriptomics, proteomics, and in vivo studies.Measurements and Main Results: Macrophage phagocytosis of A. fumigatus enabled control of 90% of fungal germination. However, fungal germination in the late phagosome led to macrophage necrosis. During programmed necroptosis, we observed frequent cell-cell transfer of A. fumigatus between macrophages, which assists subsequent control of germination in recipient macrophages. Lateral transfer occurred through actin-dependent exocytosis of the late endosome in a vasodilator-stimulated phosphoprotein envelope. Its relevance to the control of fungal germination was also shown by direct visualization in our zebrafish aspergillosis model in vivo. The calcineurin inhibitor FK506 (tacrolimus) reduced cell death and lateral transfer in vitro by 50%. This resulted in uncontrolled fungal germination in macrophages and also resulted in hyphal escape.Conclusions: These observations identify programmed, necrosisdependent lateral transfer of A. fumigatus between macrophages as an important host strategy for controlling fungal germination. This process is critically dependent on calcineurin. Our studies provide fundamental insights into the pathogenesis of pulmonary aspergillosis in the immunocompromised host.

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“…Recently, invasive aspergillosis is on the rise and very difficult to diagnose in patients with severe critical illness (but without chronic underlying disease and certainly without host factors as defined by the EORTC/ Mycosis Study Group). Especially when the patient is mechanically ventilated, medical imaging is particularly problematic due to non-specific imaging finding in most of those patients (11,12). However, the incidence among immunocompetent patients without acute or chronic critical illness is rather low (9,10).…”

Section: Discussionmentioning

confidence: 99%

Airway centered invasive pulmonary aspergillosis in an immunocompetent patient: case report and literature review

Kim¹,

Lee²,

Kim³

et al. 2016

J. Thorac. Dis.

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Invasive pulmonary aspergillosis is a major problem that occurs in severely immunocompromised patients. Airway centered invasive pulmonary aspergillosis is rare in patients with normal immunity or those without critical illness. Computed tomography (CT) is a very useful diagnostic modality, yielding characteristic imaging findings for early diagnosis of this infection in immunocompromised and immunocompetent patients. We describe the case of an immunocompetent patient with airway centered invasive aspergillosis, who was successfully treated with voriconazole.

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Epidemiology of invasive aspergillosis in critically ill patients: clinical presentation, underlying conditions, and outcomes

Cited by 313 publications

References 52 publications

Intensive care medicine research agenda on invasive fungal infection in critically ill patients

Intensive care medicine research agenda on invasive fungal infection in critically ill patients

Calcineurin Orchestrates Lateral Transfer of Aspergillus fumigatus during Macrophage Cell Death

Airway centered invasive pulmonary aspergillosis in an immunocompetent patient: case report and literature review

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