Aspergillosis in the ICU: Hidden Enemy or Bogeyman?
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ABSTRACT:
SUBMITTER: Aberegg SK
PROVIDER: S-EPMC8048762 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC8048741 | biostudies-literature
Project description: Not available
| S-EPMC7560816 | biostudies-literature
Project description:Objective: To assess the effectiveness of three general prognostic models (APACHE II, SAPS II, and SOFA) with serum galactomannan antigen in a clinically suspected invasive aspergillosis (IA) subpopulation admitted to a respiratory medicine ICU and to identify azole-resistant Aspergillus fumigatus (ARAF) cases. Methodology and Results: A total of 235 clinically suspected IA patients were prospectively enrolled and observed 30-day mortality was 29.7%. The three general models showed poor discrimination assessed by area under receiver operating characteristic (ROC) curves (AUCs, <0.7) and good calibration (p = 0.92, 0.14, and 0.13 for APACHE II, SAPS II, and SOFA, respectively), evaluated using Hosmer-Lemeshow goodness-of-fit tests. However, discrimination was significantly better with galactomannan values (AUC, 0.924). In-vitro antifungal testing revealed higher minimum inhibitory concentration (MIC) for 12/34 isolates (35.3%) whereas azole resistance was noted in 40% of Aspergillus fumigatus isolates (6/15) with two hotspot cyp51A mutations, G54R and P216L. Conclusions: Patients diagnosed with putative and probable IA (71.4% and 34.6%, respectively), had high mortality. The general prognostic model APACHE II seemed fairly accurate for this subpopulation. However, the use of local GM cut-offs calculated for mortality, may help the intensivists in prompt initiation or change of therapy for better outcome of patients. In addition, the high MICs highlight the need of antifungal surveillance to know the local resistance rate which might aid in patient treatment.
| S-EPMC8625311 | biostudies-literature
Project description:IntroductionThe incidence of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is increasing, and early diagnosis of the disease and treatment with antifungal drugs is critical for patient survival. Serum biomarker tests for IPA typically give false-negative results in non-neutropenic patients, and galactomannan (GM) detection, the preferred diagnostic test for IPA using bronchoalveolar lavage (BAL), is often not readily available. Novel approaches to IPA detection in ICU patients are needed. In this multicenter study, we evaluated the performance of an Aspergillus lateral-flow device (LFD) test for BAL IPA detection in critically ill patients.MethodsA total of 149 BAL samples from 133 ICU patients were included in this semiprospective study. Participating centers were the medical university hospitals of Graz, Vienna and Innsbruck in Austria and the University Hospital of Mannheim, Germany. Fungal infections were classified according to modified European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria.ResultsTwo patients (four BALs) had proven IPA, fourteen patients (sixteen BALs) had probable IPA, twenty patients (twenty-one BALs) had possible IPA and ninety-seven patients (one hundred eight BALs) did not fulfill IPA criteria. Sensitivity, specificity, negative predictive value, positive predictive value and diagnostic odds ratios for diagnosing proven and probable IPA using LFD tests of BAL were 80%, 81%, 96%, 44% and 17.6, respectively. Fungal BAL culture exhibited a sensitivity of 50% and a specificity of 85%.ConclusionLFD tests of BAL showed promising results for IPA diagnosis in ICU patients. Furthermore, the LFD test can be performed easily and provides rapid results. Therefore, it may be a reliable alternative for IPA diagnosis in ICU patients if GM results are not rapidly available.Trial registrationClinicalTrials.gov NCT02058316. Registered 20 January 2014.
| S-EPMC4421996 | biostudies-literature
Project description:The main objective of this study was to determine the incidence of invasive pulmonary aspergillosis (IPA) in patients with coronavirus disease 2019 (COVID-19) admitted to the intensive care unit (ICU), and to describe the patient characteristics associated with IPA occurrence and to evaluate its impact on prognosis. We conducted a retrospective cohort study including all successive COVID-19 patients, hospitalized in four ICUs, with secondary deterioration and one or more respiratory samples sent to the mycology department. We used a strengthened IPA testing strategy including seven mycological criteria. Patients were classified as probable IPA according to the European Organization for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) classification if immunocompromised, and according to the recent COVID-19-associated IPA classification otherwise. Probable IPA was diagnosed in 21 out of the 366 COVID-19 patients (5.7%) admitted to the ICU and in the 108 patients (19.4%) who underwent respiratory sampling for deterioration. No significant differences were observed between patients with and without IPA regarding age, gender, medical history and severity on admission and during hospitalization. Treatment with azithromycin for ≥3 days was associated with the diagnosis of probable IPA (odds ratio 3.1, 95% confidence interval 1.1-8.5, p = 0.02). A trend was observed with high-dose dexamethasone and the occurrence of IPA. Overall mortality was higher in the IPA patients (15/21, 71.4% versus 32/87, 36.8%, p < 0.01). IPA is a relatively frequent complication in severe COVID-19 patients and is responsible for increased mortality. Azithromycin, known to have immunomodulatory properties, may contribute to increase COVID-19 patient's susceptibility to IPA.
| S-EPMC7733556 | biostudies-literature
Project description:ObjectiveThis study was conducted to get a complete clinical and mycological picture of invasive aspergillosis (IA) in respiratory medicine ICU of a tertiary care hospital.PatientsFrom the cohort of 235 patients only one had proven IA. Based on AspICU algorithm, 21 had putative IA (8.9%), 12 were colonised (5.1%).ResultsAdjusting the confounding factors, significant risk factors for IA were chronic obstructive pulmonary disease (COPD), temperature of ≥38°C, pneumonia and acute respiratory distress syndrome (ARDS). The best predictor of IA was AspICU algorithm (AUC, 1) followed by serum galactomannan antigen (GM) cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.822). For 37% of patients, IA diagnoses was made earlier with serum GM than radiology. There were 70/235 (29.8%) deaths within 30 days of enrolment in the study. Aspergillus culture positivity (34/235, 14.5%) was associated with very high mortality (27/34, 79.4%), (p<0.05). The best predictor of mortality was GM cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.835).ConclusionThis study imparts the focus on relatively underestimated Aspergillus infections prevalent in ICUs. The AspICU algorithm was found to be useful over others for IA diagnosis. The prognostic usefulness of serum GM antigen detection test highlighted overlooking the same may not be rewarding for the outcome of IA suspected ICU subpopulation.
| S-EPMC5912734 | biostudies-literature
Project description:BackgroundA high prevalence of COVID-19 associated pulmonary aspergillosis (CAPA) has been reported, though histopathological evidence is frequently lacking. To assess the clinical significance of Aspergillus species in respiratory samples of mechanically ventilated COVID-19 patients, we implemented routine screening for Aspergillus in tracheal aspirate (TA).Patients/methodsFrom all adult COVID-19 patients admitted to the intensive care unit (ICU), TA samples were collected twice a week for Aspergillus screening by PCR and or culture. Bronchoalveolar lavage (BAL) sampling was performed in patients with a positive screening result if possible. Clinical information was obtained from the electronic patient record and patients were categorised according to the recently published consensus case definition for CAPA.ResultsOur study population consisted of 63 predominantly (73%) male patients, with a median age of 62 years and total median ICU stay of 18 days. Aspergillus species were present in TA screening samples from 15 patients (24%), and probable CAPA was diagnosed in 11 (17%) patients. Triazole resistance was detected in one patient (14%). Concordance between TA and BAL was 86%, and all TA culture positives were confirmed in BAL. We were able to withhold treatment in three of fifteen patients with positive screening (20%) but negative BAL results.ConclusionsPositive culture, molecular detection and or antigen detection of Aspergillus species do not equal infection. Until we understand the clinical relevance of Aspergillus species detected in respiratory samples of COVID-19 patients, minimal-invasive screening by TA is a feasible method to monitor patients. Positive screening results should be an indication to perform a BAL to rule out upper airway colonisation.
| S-EPMC8014245 | biostudies-literature
Project description:BackgroundCOVID-19-associated invasive pulmonary aspergillosis (CAPA) is associated with increased mortality. Cases of CAPA caused by azole-resistant Aspergillus fumigatus strains have been reported.ObjectivesTo analyse the twelve-month CAPA prevalence in a German tertiary care hospital and to characterise clinical A. fumigatus isolates from two German hospitals by antifungal susceptibility testing and microsatellite genotyping.Patients/methodsRetrospective observational study in critically ill adults from intensive care units with COVID-19 from 17 February 2020 until 16 February 2021 and collection of A. fumigatus isolates from two German centres. EUCAST broth microdilution for four azole compounds and microsatellite PCR with nine markers were performed for each collected isolate (N = 27) and additional for three non-COVID A. fumigatus isolates.Resultswelve-month CAPA prevalence was 7.2% (30/414), and the rate of azole-resistant A. fumigatus isolates from patients with CAPA was 3.7% with detection of one TR34/L98H mutation. The microsatellite analysis revealed no major clustering of the isolates. Sequential isolates mainly showed the same genotype over time.ConclusionsOur findings demonstrate similar CAPA prevalence to other reports and a low azole-resistance rate. Genotyping of A. fumigatus showed polyclonal distribution except for sequential isolates.
| S-EPMC9115305 | biostudies-literature
Project description: Not available
| S-EPMC8340564 | biostudies-literature
Project description:The granule-exocytosis pathway is the major mechanism via which cytotoxic lymphocytes eliminate virus-infected and tumor cells. In this pathway, cytotoxic lymphocytes release granules containing the pore-forming protein perforin and a family of serine proteases known as granzymes into the immunological synapse. Pore-formation by perforin facilitates entry of granzymes into the target cell, where they can activate various (death) pathways. Humans express five different granzymes, of which granzymes A and B have been most extensively characterized. However, much less is known about granzyme M (GrM). Recently, structural analysis and advanced proteomics approaches have determined the primary and extended specificity of GrM. GrM functions have expanded over the past few years: not only can GrM efficiently induce cell death in tumor cells, it can also inhibit cytomegalovirus replication in a noncytotoxic manner. Finally, a role for GrM in lipopolysaccharide-induced inflammatory responses has been proposed. In this review, we recapitulate the current status of GrM expression, substrate specificity, functions, and inhibitors.
| S-EPMC3921602 | biostudies-literature