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Medicina 2023Invasive aspergillosis (IA) is a serious disease with high mortality. There are several risk factors and in-hospital outbreaks related with construction have been...
Invasive aspergillosis (IA) is a serious disease with high mortality. There are several risk factors and in-hospital outbreaks related with construction have been described. An entity related to COVID-19 infection, known as COVID-19 associated pulmonary aspergillosis (CAPA), has recently appeared. Early and appropriate treatment is of paramount importance, especially in immunocompromised and critically ill patients. Diagnosis is based on recognition of predisposing factors, clinical signs, imaging, direct examination, culture, histopathology, and biomarkers such as galactomannan. The drug of choice is voriconazole, but alternative therapies must be taken into account given the increasing presence of resistant isolates.
Topics: Humans; COVID-19; Aspergillosis; COVID-19 Testing
PubMed: 36774601
DOI: No ID Found -
The Cochrane Database of Systematic... Dec 2015Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Invasive aspergillosis is the most common life-threatening opportunistic invasive mycosis in immunocompromised patients. A test for invasive aspergillosis should neither be too invasive nor too great a burden for the already weakened patient. The serum galactomannan enzyme-linked immunosorbent assay (ELISA) seems to have the potential to meet both requirements.
OBJECTIVES
To obtain summary estimates of the diagnostic accuracy of galactomannan detection in serum for the diagnosis of invasive aspergillosis.
SEARCH METHODS
We searched MEDLINE, EMBASE and Web of Science with both MeSH terms and text words for both aspergillosis and the sandwich ELISA. We checked the reference lists of included studies and review articles for additional studies. We conducted the searches in February 2014.
SELECTION CRITERIA
We included cross-sectional studies, case-control designs and consecutive series of patients assessing the diagnostic accuracy of galactomannan detection for the diagnosis of invasive aspergillosis in patients with neutropenia or patients whose neutrophils are functionally compromised. The reference standard was composed of the criteria given by the European Organization for Research and Treatment of Cancer (EORTC) and the Mycoses Study Group (MSG).
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed quality and extracted data. We carried out meta-analysis using the bivariate method. We investigated sources of heterogeneity by adding potential sources of heterogeneity to the model as covariates.
MAIN RESULTS
We included 54 studies in the review (50 in the meta-analyses), containing 5660 patients, of whom 586 had proven or probable invasive aspergillosis. When using an optical density index (ODI) of 0.5 as a cut-off value, the sensitivity of the test was 82% (73% to 90%) and the specificity was 81% (72% to 90%). At a cut-off value of 1.0 ODI, the sensitivity was 72% (65% to 80%) and the specificity was 88% (84% to 92%). At a cut-off value of 1.5 ODI, the sensitivity was 61% (47% to 75%) and the specificity was 93% (89% to 97%). None of the potential sources of heterogeneity had a statistically significant effect on either sensitivity or specificity.
AUTHORS' CONCLUSIONS
If we used the test at a cut-off value of 0.5 ODI in a population of 100 patients with a disease prevalence of 9% (overall median prevalence), two patients who have invasive aspergillosis would be missed (sensitivity 82%, 18% false negatives), and 17 patients would be treated unnecessarily or referred unnecessarily for further testing (specificity 81%, 19% false negatives). If we used the test at a cut-off value of 1.5 in the same population, that would mean that four invasive aspergillosis patients would be missed (sensitivity 61%, 39% false negatives), and six patients would be treated or referred for further testing unnecessarily (specificity 93%, 7% false negatives). These numbers should, however, be interpreted with caution because the results were very heterogeneous.
Topics: Aspergillosis; Biomarkers; Galactose; Humans; Immunocompromised Host; Mannans; Opportunistic Infections; Sensitivity and Specificity
PubMed: 26716951
DOI: 10.1002/14651858.CD007394.pub2 -
American Journal of Respiratory and... Aug 2023
Topics: Humans; Influenza, Human; COVID-19; Pulmonary Aspergillosis; Invasive Pulmonary Aspergillosis
PubMed: 37348113
DOI: 10.1164/rccm.202306-1022ED -
MBio Jun 2022The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive...
The French National Reference Center for Invasive Mycoses and Antifungals leads an active and sustained nationwide surveillance program on probable and proven invasive fungal diseases (IFDs) to determine their epidemiology in France. Between 2012 and 2018, a total of 10,886 IFDs were recorded. The incidence increased slightly over time (2.16 to 2.36/10,000 hospitalization days, = 0.0562) in relation with an increase of fungemia incidence (1.03 to 1.19/10,000, = 0.0023), while that of other IFDs remained stable. The proportion of ≥65-year-old patients increased from 38.4% to 45.3% ( < 0.0001). Yeast fungemia ( = 5,444) was due mainly to Candida albicans (55.6%) with stable proportions of species over time. Echinocandins became the main drug prescribed (46.7% to 61.8%), but global mortality rate remained unchanged (36.3% at 1 month). Pneumocystis jirovecii pneumonia ( = 2,106) was diagnosed mostly in HIV-negative patients (80.7%) with a significantly higher mortality than in HIV-positive patients (21.9% versus 5.4% at 1 month, < 0.0001). Invasive aspergillosis ( = 1,661) and mucormycosis ( = 314) were diagnosed mostly in hematology (>60% of the cases) with a global mortality rate of 42.5% and 59.3%, respectively, at 3 months and significant changes in diagnosis procedure over time. More concurrent infections were also diagnosed over time (from 5.4% to 9.4% for mold IFDs, = 0.0115). In conclusion, we observed an aging of patients with IFD with a significant increase in incidence only for yeast fungemia, a trend toward more concurrent infections, which raises diagnostic and therapeutic issues. Overall, global survival associated with IFDs has not improved despite updated guidelines and new diagnostic tools. The epidemiology of invasive fungal diseases (IFDs) is hard to delineate given the difficulties in ascertaining the diagnosis that is often based on the confrontation of clinical and microbiological criteria. The present report underlines the interest of active surveillance involving mycologists and clinicians to describe the global incidence and that of the main IFDs. Globally, although the incidence of Pneumocystis pneumonia, invasive aspergillosis, and mucormycosis remained stable over the study period (2012 to 2018), that of yeast fungemia increased slightly. We also show here that IFDs seem to affect older people more frequently. The most worrisome observation is the lack of improvement in the global survival rate associated with IFDs despite the increasing use of more sensitive diagnostic tools, the availability of new antifungal drugs very active in clinical trials, and a still low/marginal rate of acquired resistance in France. Therefore, other tracks of improvement should be investigated actively.
Topics: Aged; Antifungal Agents; Aspergillosis; Fungemia; Humans; Invasive Fungal Infections; Mucormycosis; Pneumonia, Pneumocystis; Watchful Waiting
PubMed: 35499498
DOI: 10.1128/mbio.00920-22 -
Frontiers in Cellular and Infection... 2023The identification of by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of...
PURPOSE
The identification of by metagenomic next-generation sequencing (mNGS) remains a challenging task due to the difficulty of nucleic acid extraction. The objective of this study was to determine whether mNGS could provide an accurate and efficient method for detecting invasive pulmonary (IPA) in immunocompromised patients (ICP).
METHODS
A total of 133 ICP admitted to the ICU between January 2020 and September 2022 were enrolled in the study, of which 46 were diagnosed with IPA and 87 were non-IPA cases. The bronchoalveolar lavage fluid (BALF) was analyzed for the presence of and other co-pathogens using mNGS, and its diagnostic performance was compared to conventional microbial tests (CMTs) that included smear, cultures, serum and BALF galactomannan (GM) test. Clinical composite diagnosis was used as the reference standard.
RESULTS
mNGS had a sensitivity, specificity, and accuracy of 82.6%, 97.7%, and 92.5%, respectively, in diagnosing IPA. These findings were comparable to those of the combination of multiple CMTs. Interestingly, the sensitivity of mNGS was superior to that of any single CMT method, as demonstrated by comparisons with smears (8.7%, < 0.001), culture (39.1%, < 0.001), serum GM (23.9%, < 0.001) and BALF GM (69.6%, = 0.031). mNGS was capable of accurately distinguish strains of genus, with a consistency of 77.8% with culture. Furthermore, mNGS also identified , , , and spp. in culture-negative cases. The sequencing reads of by mNGS exhibited extensive variation, ranging from 11 to1702. A positive correlation was observed between the optical density index of BALF GM and unique reads by mNGS (r = 0.607, = 0.001) in BALF-GM positive patients. Notably, mNGS was able to diagnose 35 out of 37 cases with mixed infection, with and being the most common co-pathogens.
CONCLUSIONS
mNGS presents a feasible and remarkably sensitive approach for detecting in ICP, thereby serving as a valuable adjunctive tool to CMT. Furthermore, mNGS's ability to accurately identify fungal species and co-pathogens can assist in guiding appropriate antimicrobial therapy.
Topics: Humans; Retrospective Studies; Aspergillosis; Invasive Pulmonary Aspergillosis; High-Throughput Nucleotide Sequencing; Immunocompromised Host
PubMed: 38188627
DOI: 10.3389/fcimb.2023.1209724 -
Medical Mycology Journal 2016Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged... (Review)
Review
Invasive aspergillosis (IA) is still one of the leading causes of morbidity and mortality in hematological patients, although its outcome has been improving. Prolonged and profound neutropenia in patients receiving intensive chemotherapy for acute leukemia and stem cell transplantation is a major risk factor for IA. Allogeneic stem cell transplant recipients with graft-versus-host disease and corticosteroid use are also at high risk. Management in a protective environment with high efficiency particular air (HEPA) filter is generally recommended to prevent aspergillosis in patients with prolonged and profound neutropenia. Antifungal prophylaxis against Aspergillus species should be considered in patients with past history of aspergillosis or colonization of Aspergillus species, at facilities with high incidence of IA and those without a protective environment. Early diagnosis and prompt antifungal treatment is important to improve outcome. Imaging studies such as computed tomography and biomarkers such as galactomannan antigen and β-D-glucan are useful for early diagnosis. Empirical antifungal treatment based on persistent or recurrent fever during neutropenia despite broad-spectrum antibiotic therapy is generally recommended in high-risk patients. Alternatively, a preemptive treatment strategy has recently been proposed in the context of progress in the early diagnosis of IA based on the results of imaging studies and biomarkers. Voriconazole is recommended for initial therapy for IA. Liposomal amphotericin B is considered as alternative initial therapy. Combination antifungal therapy of echinocandin with voriconazole or liposomal amphotericin B could be a choice for refractory cases.
Topics: Amphotericin B; Antifungal Agents; Antineoplastic Agents; Aspergillosis; Biomarkers; Echinocandins; Hematologic Neoplasms; Humans; Neutropenia; Opportunistic Infections; Risk Factors; Stem Cell Transplantation; Tomography, X-Ray Computed; Voriconazole
PubMed: 27251320
DOI: 10.3314/mmj.57.J77 -
Journal of Molecular Biology Oct 2019The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans... (Review)
Review
The genus Aspergillus is ubiquitous in the environment and contains a number of species, primarily A. fumigatus, that cause mold-associated disease in humans. Humans inhale several hundred to several thousand Aspergillus conidia (i.e., vegetative spores) daily and typically clear these in an asymptomatic manner. In immunocompromised individuals, Aspergillus conidia can germinate into tissue-invasive hyphae, disseminate, and cause invasive aspergillosis. In this review, we first discuss novel concepts in host defense against Aspergillus infections and emphasize new insights in fungal recognition and signaling, innate immune activation, and fungal killing. Second, the review focuses on novel concepts of Aspergillus pathogenesis and highlights emerging knowledge regarding fungal strain heterogeneity, stress responses, and metabolic adaptations on infectious outcomes. Mechanistic insight into the host-pathogen interplay is thus critical to define novel druggable fungal targets and to exploit novel immune-based strategies to improve clinical outcomes associated with aspergillosis in vulnerable patient populations.
Topics: Animals; Aspergillosis; Aspergillus; Cell Wall; Humans; Immunity, Innate; Mycology
PubMed: 30954573
DOI: 10.1016/j.jmb.2019.03.027 -
Medicine Jul 2015Invasive aspergillosis (IA) has poor prognosis in immunocompromised patients. Skin manifestations, when present, should contribute to an early diagnosis. The authors... (Observational Study)
Observational Study Review
Invasive aspergillosis (IA) has poor prognosis in immunocompromised patients. Skin manifestations, when present, should contribute to an early diagnosis. The authors aimed to provide prevalence data and a clinical and histologic description of cutaneous manifestations of primary cutaneous IA (PCIA) and secondary CIA (SCIA) in a unique clinical series of IA and present the results of an exhaustive literature review of CIA. Cases of proven and probable IA with cutaneous manifestations were retrospectively extracted from those registered between 2005 and 2010 in a prospective multicenter aspergillosis database held by the National Reference Center for Invasive Mycoses and Antifungals, Pasteur Institute, France. Patients were classified as having PCIA (i.e., CIA without extracutaneous manifestations) or SCIA (i.e., disseminated IA). Among the 1,410 patients with proven or probable IA, 15 had CIA (1.06%), 5 PCIA, and 10 SCIA. Hematological malignancies were the main underlying condition (12/15). Patients with PCIA presented infiltrated and/or suppurative lesions of various localizations not related to a catheter site (4/5), whereas SCIA was mainly characterized by disseminated papules and nodules but sometimes isolated nodules or cellulitis. Histologic data were available for 11 patients, and for 9, similar for PCIA and SCIA, showed a dense dermal polymorphic inflammatory infiltrate, with the epidermis altered in PCIA only. Periodic acid Schiff and Gomori-Grocott methenamine silver nitrate staining for all but 2 biopsies revealed hyphae compatible with Aspergillus. Aspergillus flavus was isolated in all cases of PCIA, with Aspergillus fumigatus being the most frequent species (6/10) in SCIA. Two out 5 PCIA cases were treated surgically. The 3-month survival rate was 100% and 30% for PCIA and SCIA, respectively. Our study is the largest adult series of CIA and provides complete clinical and histologic data for the disease. Primary cutaneous IA should be recognized early, and cases of extensive necrosis should be treated surgically; its prognosis markedly differs from that for SCIA. Any suppurative, necrotic, papulonodular, or infiltrated skin lesion in an immunocompromised patient should lead to immediate biopsy for histologic analysis and mycological skin direct examination and culture.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antifungal Agents; Aspergillosis; Child; Child, Preschool; Female; France; Humans; Infant; Male; Middle Aged; Prevalence; Retrospective Studies; Skin; Young Adult
PubMed: 26131805
DOI: 10.1097/MD.0000000000001018 -
Epidemiology and Infection Oct 2023Aspergillosis is a rising concern worldwide; however, its prevalence is not well documented in China. This retrospective study determined epidemiology and antifungal...
Aspergillosis is a rising concern worldwide; however, its prevalence is not well documented in China. This retrospective study determined epidemiology and antifungal susceptibilities at Meizhou People's Hospital, South China. From 2017 to 2022, the demographic, clinical, and laboratory data about aspergillosis were collected from the hospital's records and analysed using descriptive statistics, chi-square test, and ANOVA. Of 474 aspergillosis cases, (75.32%) was the most common, followed by (9.92%), (8.86%), and (5.91%). A 5.94-fold increase in aspergillosis occurred during the study duration, with the highest cases reported from the intensive care unit (52.74%) - chronic pulmonary aspergillosis (79.1%) and isolated from sputum (62.93%). Only 38 (8.02%) patients used immunosuppressant drugs, while gastroenteritis (5.7%), haematologic malignancy (4.22%), and cardiovascular disease (4.22%) were the most prevalent underlying illnesses. In the wild-type (WT) isolates against amphotericin B (99.1%) were higher than triazoles (97-98%), whereas, in non- species, the triazole (95-100%) WT proportion was greater than amphotericin B (91-95%). Additionally, there were significantly fewer WT isolates for itraconazole and posaconazole in outpatients than inpatients. These findings may aid in better understanding and management of aspergillosis in the region.
Topics: Humans; Antifungal Agents; Amphotericin B; Retrospective Studies; Voriconazole; Aspergillus; Aspergillosis; Microbial Sensitivity Tests
PubMed: 37846567
DOI: 10.1017/S095026882300167X -
Virulence Aug 2017Filamentous fungi of the genus Aspergillus are responsible for several superficial and invasive infections and allergic syndromes. The risk of infection and its clinical... (Review)
Review
Filamentous fungi of the genus Aspergillus are responsible for several superficial and invasive infections and allergic syndromes. The risk of infection and its clinical outcome vary significantly even among patients with similar predisposing clinical factors and pathogen exposure. There is increasing evidence that the individual microbiome supervises the outcome of the host-fungus interaction by influencing mechanisms of immune regulation, inflammation, metabolism, and other physiological processes. Microbiome-mediated mechanisms of resistance allow therefore the control of fungal colonization, preventing the onset of overt disease, particularly in patients with underlying immune dysfunction. Here, we review this emerging area of research and discuss the contribution of the microbiota (and its dysbiosis), including its immunoregulatory properties and relationship with the metabolic activity of commensals, to respiratory fungal diseases. Finally, we highlight possible strategies aimed at decoding the microbiome-metabolome dialog and at its exploitation toward personalized medical interventions in patients at high risk of infection.
Topics: Animals; Aspergillosis; Aspergillus; Dysbiosis; Fungi; Host-Pathogen Interactions; Humans; Inflammation; Metabolome; Mice; Microbiota; Mycoses; Precision Medicine; Respiratory Tract Infections; Signal Transduction; Symbiosis
PubMed: 27820674
DOI: 10.1080/21505594.2016.1257458