Cases Of Invasive Pulmonary Aspergillosis Research Articles

Value Evaluation of Quantitative Aspergillus fumigatus-Specific IgG Antibody Test in the Diagnosis of Non-neutropenic Invasive Pulmonary Aspergillosis.

The role of Aspergillus-specific IgG antibody test in the diagnosis of non-neutropenic invasive pulmonary aspergillosis (IPA) is still uncertain, and related studies are also limited. This study aims to evaluate the quantitative test value of Aspergillus fumigatus-specific IgG antibody in non-neutropenic IPA, which could provide additional evidence for related clinical diagnosis. This prospective study collected clinical data of suspected IPA patients from January, 2020 to December, 2022, and patients were divided into two groups, IPA and non-IPA. The study analyzed clinical characteristics and diagnostic value of Aspergillus-specific IgG antibody test, using the receiver operating characteristic (ROC) curve to evaluate diagnostic efficacy. The study enrolled 59 IPA cases and 68 non-IPA cases, the average admission age of IPA group was 63.2±9.6 (33-79), and the gender ratio (male:female) of IPA group was 42:17. The proportion of patients with history of smoking and COPD were higher in IPA group (59.3% vs 39.7%, P=0.027; 33.9% vs 14.7%, P =0.011, respectively). The level of Aspergillus fumigatus-specific IgG antibody in IPA group was significantly higher than non-IPA group (202.1±167.0 vs 62.6±58.0, P<0.001). The area under the ROC curve was 0.799 (95%CI: 0.718, 0.865 P<0.001), and the cut-off with best diagnostic efficacy was 91 AU/mL. Immunological test plays an important role in the diagnosis of pulmonary aspergillosis, and Aspergillus-specific IgG antibody test has the good diagnostic value in non-neutropenic IPA.

Clinical utility of metagenomic next-generation sequencing in the diagnosis of invasive pulmonary aspergillosis in acute exacerbation of chronic obstructive pulmonary disease patients in the intensive care unit.

To explore the clinical utility of metagenomic next-generation sequencing (mNGS) in diagnosing invasive pulmonary aspergillosis (IPA) among patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in the intensive care unit (ICU). A retrospective analysis was conducted on patients with AECOPD admitted to the ICU of Xinxiang Central Hospital in Henan Province, China, between March 2020 and September 2023, suspected of having IPA. Bronchoalveolar lavage fluid (BALF) samples were collected for fungal culture, the galactomannan (GM) test, and mNGS. Based on host factors, clinical features, and microbiological test results, patients were categorized into 62 cases of IPA and 64 cases of non-IPA. Statistical analysis was performed to compare the diagnostic efficacy of fungal culture, the serum and BALF GM test, and mNGS detection for IPA in patients with AECOPD. 1. The sensitivity and specificity of mNGS in diagnosing IPA were 70.9% and 71.8% respectively, with the sensitivity of mNGS surpassing that of fungal culture (29.0%, P<0.01), serum GM test (35.4%, P<0.01), and BALF GM test (41.9%, P<0.05), albeit with slightly lower specificity compared to fungal culture (90.6%, P >0.05), serum GM test (87.5%, P >0.05), and BALF GM test (85.9%, P >0.05).Combining fungal culture with the GM test and mNGS resulted in a sensitivity of 80.6% and a specificity of 92.2%, underscoring a superior diagnostic rate compared to any single detection method. 2.mNGS accurately distinguished strains of the Aspergillus genus. 3.The area under the ROC curves of mNGS was 0.73, indicating good diagnostic performance. 4.The detection duration for mNGS is shorter than that of traditional fungal culture and GM testing. mNGS presents a pragmatic and highly sensitive approach, serving as a valuable complementary tool to conventional microbiological tests (CMT). Our research demonstrated that, compared to fungal culture and GM testing, mNGS exhibits superior diagnostic capability for IPA among patients with AECOPD. Integration of mNGS with established conventional methods holds promise for improving the diagnosis rate of IPA.

Clinical Implementation of β-Tubulin Gene-Based Aspergillus Polymerase Chain Reaction for Enhanced Aspergillus Diagnosis in Patients with Hematologic Diseases: A Prospective Observational Study.

The β-tubulin (benA) gene is a promising target for the identification of Aspergillus species. Assessment of the clinical implementation and performance of benA gene-based Aspergillus polymerase chain reaction (PCR) remains warranted. In this study, we assessed the analytical performance of the BenA probe PCR in comparison with the Aspergenius kit. We prospectively collected bronchoalveolar lavage (BAL) fluid via diagnostic bronchoscopy from adult patients with hematologic diseases. BenA gene-based multiplex real-time PCR and sequential melting temperature analysis were performed to detect the azole resistance of Aspergillus fumigatus. In total, 76 BAL fluids in 75 patients suspicious of invasive pulmonary aspergillosis (IPA) were collected. Before the application of PCR, the prevalence of proven and probable IPA was 32.9%. However, after implementing the benA gene-based PCR, 15.8% (12 out of 76) of potential IPA cases were reclassified as probable IPA. The analytical performance of the BenA probe PCR in BAL samples was comparable to that of the Aspergenius kit. The diagnostic performance was as follows: sensitivity, 52.0%; specificity, 64.7%; positive predictive value, 41.9%; negative predictive value, 73.3%; positive likelihood ratio, 1.473; and negative likelihood ratio, 0.741. Moreover, benA gene-based Aspergillus PCR discriminated all major sections of Aspergillus, including cryptic species such as Aspergillus tubingensis. Sequential melting temperature analysis successfully detected 2 isolates (15.4%) of A. fumigatus carrying resistant mutations. BenA gene-based Aspergillus PCR with melting temperature analysis enhances diagnostic accuracy and detects not only cryptic species but also resistant mutations of A. fumigatus. It shows promise for clinical applications in the diagnosis of IPA.

Retrospective Multicenter Evaluation of the VirClia Galactomannan Antigen Assay for the Diagnosis of Pulmonary Aspergillosis with Bronchoalveolar Lavage Fluid Samples from Patients with Hematological Disease.

Galactomannan (GM) testing of bronchoalveolar lavage (BAL) fluid samples has become an essential tool to diagnose invasive pulmonary aspergillosis (IPA) and is part of diagnostic guidelines. Enzyme-linked immunosorbent assays (ELISAs) (enzyme immunoassays [EIAs]) are commonly used, but they have a long turnaround time. In this study, we evaluated the performance of an automated chemiluminescence immunoassay (CLIA) with BAL fluid samples. This was a multicenter retrospective study in the Netherlands and Belgium. BAL fluid samples were collected from patients with underlying hematological diseases with a suspected invasive fungal infection. Diagnosis of IPA was based on the 2020 European Organisation for Research and Treatment of Cancer (EORTC)/Mycoses Study Group Education and Research Consortium (MSGERC) consensus definitions. GM results were reported as optical density index (ODI) values. ODI cutoff values for positive results that were evaluated were 0.5, 0.8, and 1.0 for the EIA and 0.16, 0.18, and 0.20 for the CLIA. Probable IPA cases were compared with two control groups, one with no evidence of IPA and another with no IPA or possible IPA. Qualitative agreement was analyzed using Cohen's κ, and quantitative agreement was analyzed by Spearman's correlation. We analyzed 141 BAL fluid samples from 141 patients; 66 patients (47%) had probable IPA, and 56 cases remained probable IPA when the EIA GM result was excluded as a criterion, because they also had positive culture and/or duplicate positive PCR results. Sixty-three patients (45%) had possible IPA and 12 (8%) had no IPA. The sensitivity and specificity of the two tests were quite comparable, and the overall qualitative agreement between EIA and CLIA results was 81 to 89%. The correlation of the actual CLIA and EIA values was strong at 0.72 (95% confidence interval, 0.63 to 0.80). CLIA has similar performance, compared to the gold-standard EIA, with the benefits of faster turnaround because batching is not required. Therefore, CLIA can be used as an alternative GM assay for BAL fluid samples.

P499 A cross-sectional observational to assess the role of Bronchoalveolar lavage fluid galactomannan in the diagnosis of invasive pulmonary aspergillosis in non-neutropenic patients

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjective: This study was done to assess the role of Bronchoalveolar lavage fluid (BALF) galactomannan (GM) in the diagnosis of invasive pulmonary aspergillosis (IPA) in non-neutropenic patients and to determine the optimal cut-off value of BALF GM for diagnosing IPA in non-neutropenic hosts.MethodsWe conducted a cross-sectional observational study on 96 non-neutropenic patients of age > 18 years with suspected pulmonary infections of fungal etiology. A detailed history of predisposing conditions was obtained and routine laboratory investigations with chest computerized (CT) tomography were performed. Fiberoptic bronchoscopy under local anesthesia and sedation was done using a video bronchoscope. Bronchoalveolar lavage was done from the segment or lobe of interest instilling 60-100 ml of saline withdrawn under low pressure and the sample was tested for a battery of investigations; fungal KOH smear; fungal culture; GM by Platelia Aspergillus enzyme immunoassay; and others required for diagnosis. A protected brush specimen and transbronchial lung biopsy were done wherever feasible. The yield from the BALF GM assay was compared with diagnosis based on definitions given by EORTC/MSG excluding host factors. Patients were classified into three groups namely non-IPA, probable IPA, and proven IPA. For statistical analysis, probable and proven IPA were taken as one group i.e., the IPA group. Mann-Whitney test and Chi-Square test along with Fisher's exact test were performed for inter-group comparison between quantitative and qualitative variables respectively. The receiver operator characteristic curve was used to establish a cut-off point of BALF GM and Serum GM for predicting IPA. Sensitivity, specificity, PPV, and NPV were calculated. The McNemar test was used for the comparison of sensitivity and specificity. Inter-rater kappa agreement was used to find the strength of agreement of BALF GM, BALF culture, and BALF DM.ResultsOut of 96, 1 was diagnosed with proven IPA, 34 were probable IPA cases and 61 were not IPA cases. Chronic kidney disease (CKD) as a risk factor was more common in IPA cases compared to non-IPA cases (25.7% vs. 8.2%, P-value .019). Chest CT showed cavity in a significant number of IPA patients compared to non-IPA cases (60% vs. 29.5%, P-value .003). BALF direct microscopy, culture, and serum GM had sensitivities < 60% but specificities close to 95%. BALF GM showed promising results with a sensitivity of 88.5% and specificity of 85.7% at cutoff value of 0.8.See Figures below.Conclusions: Our study highlights the magnitude of IPA in non-neutropenic hosts with unconventional risk factors like CKD, diabetes, and the need for increased vigilance for diagnosis of IPA in such patients. We suggest a lower cut-off value of BALF GM against 1 as in EORTC/MSG criteria and consider CKD as one of the risk factors for IPA.

P210 Fungal isolates of the respiratory tract in symptomatic patients hospitalized in pulmonary units: A mycological and molecular epidemiologic study

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveFungal respiratory infections are being recognized with increasing frequency in parallel with an expanding population of immunocompromised patients. In most cases, colonization is the first step in the progression to pulmonary fungal infection. This study was designed to evaluate the distribution of fungal elements in the respiratory tract of symptomatic patients hospitalized in pulmonary units.MethodsThis descriptive cross-sectional study was carried out over a period of 2 years, from October 2017 to October 2019 in Guilan province, located in Iran's northern region. In the current study, bronchoalveolar lavage or sputum specimens were collected. All samples were analyzed by direct microscopy using KOH 10% and culture. Fungal identification was accomplished by internal transcribed spacer (ITS) and beta-tubulin sequencing. Also, in patients suspected of invasive pulmonary aspergillosis, BAL specimens were tested for galactomannan (GM) antigen.ResultsA total of 384 lung specimens [192 bronchoalveolar lavage (BAL) and 192 sputum samples] were obtained from symptomatic patients hospitalized in pulmonary units. Of these, 137 (35.67%) were positive in direct examination and culture. Among the 137 positive cases, most isolates were from male patients 86 (62.77%) and most of them were between 46 and 72 years. Candida albicans (37.22%) and C. tropicalis (21.89%) represent the two most commonly isolated species in the current study. Cough (94.16%), dyspnea (81.02%), purulent sputum (62.04%), and weight loss (56.2%) were the predominant symptoms and tuberculosis (24.81%), chemotherapy (21.89%), and diabetes mellitus (19.70%) were the predominant underlying conditions. Also, 5 cases of invasive pulmonary aspergillosis and 1 case of mucormycosis were diagnosed.Conclusion Candida albicans was the most common fungal species isolated from symptomatic patients hospitalized in pulmonary units. Tuberculosis, chemotherapy and diabetes mellitus were important underlying conditions for pulmonary fungal colonization and/or infection.

Concordancia del antígeno de galactomanano en lavado broncoalveolar broncoscópico y mini lavado broncoalveolar a ciegas

Introduction: viral pneumonias increase the susceptibility to develop fungal secondary infections. With COVID-19 pandemic, multiple cases of invasive pulmonary aspergillosis associated with COVID-19 (PAAC) have been reported, increasing mortality. It is not recommended to perform bronchoscopy during COVID-19 illness given the risk of aerosolization, so new techniques such as mini bronchoalveolar lavage (BAL) emerge. The necessity to perform a validating task for the galactomannan (GM) measurement in samples obtained through mini-BAL emerges from the absence of cutting points for the GM antigen positivity in respiratory samples non obtained by bronchoscopy.&nbsp; Aim: to validate the concordance of GM measurement in respiratory samples obtained through mini-BAL and BAL by bronchoscopy.&nbsp; Material and methods: observational and analytical prospective study. Patients admitted to intensive care unit with suspected PAAC who were asked to obtain respiratory samples for MG study were included. In all the cases, BAL and mini-BAL samples were obtained in one same procedure. It was considered positive GM with a value higher than 1.&nbsp; Results: 11 patients were studied, 6 (54.5%) cases were diagnosed positive for PAAC through bronchoscopic BAL. The mini-BAL sensitivity was 33% and the specificity 100%; predictive positive value 100% and negative predictive value 55%. The concordance correlation coefficient was 0,28% (IC -0,078 a 0,57), which showed a poor concordance between both methods. Conclusion: The GM test through mini-BAL could prove to be a fine confirmatory method, while a negative result does not discard PAAC.

Aspergillus-PCR in bronchoalveolar lavage - diagnostic accuracy for invasive pulmonary aspergillosis in critically ill patients.

The diagnosis of invasive pulmonary aspergillosis (IPA) in intensive care unit (ICU) patients is challenging, and the role of Aspergillus-PCR in bronchoalveolar lavage (BAL) is unknown. This study evaluated diagnostic accuracy of Aspergillus-PCR in BAL in IPA in three different cohorts: ICU-admitted patients with COVID-19, ICU-admitted patients without COVID-19 and immunocompromised patients. All stored available BAL samples collected from three patient groups were tested with Aspergillus-PCR (AsperGenius® ). IPA was diagnosed according to appropriate criteria for each patient group. We included 111 BAL samples from 101 patients: 52 (51%) patients admitted to ICU for COVID-19, 24 (24%) admitted to ICU for other reasons and 25 (25%) immunocompromised. There were 31 cases of IPA (28%). Aspergillus-PCR sensitivity was 64% (95% CI 47-79) and specificity 99% (95% CI 93-100). Aspergillus-PCR sensitivity was 40% (95%CI 19-64) in ICU COVID-19, 67% (95% CI 21-93) in non-COVID-19 ICU patients and 92% (95%CI 67-98) in the immunocompromised. The concordance between positive BAL-GM and BAL-PCR in patients with and without IPA was significantly lower in ICU patients (32%; 43% in COVID-19, 18% in non-COVID-19) than in the immunocompromised (92%), p<.001. Aspergillus-PCR in BAL improves the diagnostic accuracy of BAL-GM in ICU patients.

Grading of Anatomopathological Disparity in the Cases of Invasive Pulmonary Aspergillosis in wild avian species as recorded in Pigeons (Columba livia), Peafowls (Pavo cristatus), and Griffon Vultures (Gyps fulvus).

Aspergillosis which is caused by Aspergillus fumigatus, a fungal pathogen, can vary from a localized infection to severe life-threatening invasive or disseminated systemic diseases in birds. The present study aimed to evaluate and grade the anatomopathological disparity in the cases of invasive pulmonary aspergillosis (IPA) in Columba livia (pigeons), Pavo cristatus (peafowls), and Gyps fulvus (Griffon vultures). Necropsy gross lesions varied from mere congestion of lungs in P. cristatus, congestion and large necrotizing masses surrounded by a zone of hyperemia (10 mm dia) in lungs of C. livia, and typically disseminated granuloma in the lungs, air sacs, and organs of other serous membranes in G. fulvus. Histopathology varied from extensive parenchymal necrosis amidst exuberant fungal invasion in P. cristatus, multifocal to focally extensive tissue necrosis with colonies of fungal hyphae surrounded by heterophils and lymphocytes in C. livia, as well as typical mycotic granuloma embedded in the lungs, air sacs, and thoracoabdominal serous membranes with angio-invasion in G. fulvus. Based on gross and histopathological findings, we diagnosed the cases as Acute Invasive Pulmonary Aspergillosis (AIPA) in peafowls and pigeons, as well as Chronic Invasive Pulmonary Aspergillosis (CIPA) in Griffon vultures. There is a paucity of case reports on aspergillosis in wild avian species, and this report strived to document the cases of IPA in peafowls, pigeons, and vultures. This is the first report of its kind which evaluated anatomopathological disparity of IPA in pigeons, peafowls, and vultures with a proposed anatomopathological grading system which would help to understand and investigate the nature of aspergillosis in different avian hosts.

Incidence, risk factors and mortality of invasive pulmonary aspergillosis in patients with influenza: A systematic review and meta-analysis.

BackgroundAn increasing number of cases of invasive pulmonary aspergillosis (IPA) complicating influenza have been described. We performed a meta‐analysis to estimate the incidence, risk factors and outcomes of IPA in patients with influenza.MethodsA systematic search was conducted in the PubMed, EMBASE and Cochrane Library databases from their inception to 31 August 2021 for eligible studies. Data on the incidence and risk factors of and mortality due to IPA in influenza patients were pooled using a random‐effects model. Sensitivity analyses restricted to severe influenza requiring intensive care unit (ICU) support and multiple subgroup analyses were performed.ResultsFourteen studies involving 6024 hospitalised patients with influenza were included. IPA was estimated to occur in 10% of influenza patients, with a mortality rate of 52%. Similar incidence (11%) and mortality (54%) estimates for IPA were observed in the sensitivity analysis including severe cases requiring ICU support. Subgroup analysis by geographical location showed a similar IPA rate between European (10%) and non‐European (11%) studies. The IPA rate in the subset of nine studies using the modified AspICU criteria was 13%. Most subgroup analyses showed ≥50% mortality in IPA patients. Several predictors for IPA susceptibility were identified, including male sex, smoking history, chronic lung disease, influenza A (H1N1), severe conditions requiring supportive therapy, corticosteroid use before admission, solid organ transplant and haematological malignancy.ConclusionsThe IPA is common in individuals with severe influenza, and the prognosis is particularly poor. Influenza patients, especially those with high‐risk factors, should be thoroughly screened for IPA.

Invasive pulmonary aspergillosis in solid-organ transplant patients in the intensive care unit.

Solid-organ transplantation (SOT) is a well-known risk factor for invasive pulmonary aspergillosis (IPA). We report on the epidemiology and outcome of SOT patients with IPA in an intensive care unit (ICU) setting. This is a secondary study based on a subset of SOT patients from a prospective observational multicenter cohort (the AspICU project) including ICU patients with at least one Aspergillus spp. positive culture. Cases were classified as proven, probable, or putative IPA, or as Aspergillus-colonized. Mortality was reported at 12weeks. The study included 52 SOT patients (of which 18 lung, 17 liver, 12 kidney, and five heart transplants). Sixteen patients had proven IPA, 28 were categorized as putative IPA (of which only five reached a probable IPA diagnosis according to the European Organization for Research and Treatment of Cancer/Mycosis Study Group and Research Consortium criteria), and eight as Aspergillus-colonization. Among patients with IPA, 20 (45.5%) developed IPA during their ICU stay following transplantation whereas 24 patients (54.5%) had a medical ICU admission. Regarding medical imaging, nearly all IPA cases presented with non-specific findings as only nine demonstrated robust findings suggestive for invasive fungal disease. Overall, severity of the disease was reflected by a high prevalence of underlying conditions and acute organ derangements. Mortality among patients with IPA was 68%. Lung transplantation was associated with better survival (50%). IPA in SOT patients in the ICU develops in the presence of overall high severity of the disease. It rarely presents with suggestive medical imaging thereby hampering diagnosis. IPA in ICU patients with SOT carries a grim prognosis.

Molecular typing and antifungal susceptibility study of Aspergillus spp. in intensive care unit (ICU) patients in Indonesia.

Aspergillus exhibits a wide variation of susceptibility against antifungals according to genetic and environmental factors. Identification to the species level is necessary for appropriate treatment. Our objective was to determine the Aspergillus species involved in invasive pulmonary aspergillosis (IPA) among ICU patients in Jakarta, Indonesia. The incidence of IPA in ICU patients at six hospitals in Jakarta from October 2012 - January 2015 was investigated. It involved a collection of endotracheal aspirates (ETA), nasal swabs and environmental samples around the hospitals, phenotypic screening, molecular characterization, and antifungal susceptibility testing. Of the 405 patients investigated, 31 patients (7.7%) were diagnosed with putative IPA, from whom 45 Aspergillus isolates were collected. Aspergillus isolates were identified from pulmonary secretions in 24 patients, from nasal swabs in 7 patients and from both pulmonary secretions and nasal swabs in 7 patients. The phenotypic method showed 33 isolates of Aspergillus flavus (73.4%), nine Aspergillus fumigatus (20%), two Aspergillus niger (4.4%), and one Aspergillus nidulans (2.2%) isolate. Molecular identification showed 27 isolates of A. flavus (60.0%), eight isolates of A. fumigatus (17.8%), two isolates of A. niger (4.4%) and one isolate of A. nidulans (2.2%), while seven isolates (15.6%) were cryptic species or mixed isolates. Susceptibility testing showed all isolates were susceptible to amphotericin B, azoles and micafungin. Aspergillus flavus was the main causative organism in IPA cases in Jakarta, followed by A. fumigatus.

A review of significance of Aspergillus detection in airways of ICU COVID-19 patients.

It is now well known that patients with SARS‐CoV‐2 infection admitted in ICU and mechanically ventilated are at risk of developing invasive pulmonary aspergillosis (IPA). Nevertheless, symptomatology of IPA is often atypical in mechanically ventilated patients, and radiological aspects in SARS‐CoV‐2 pneumonia and IPA are difficult to differentiate. In this context, the significance of the presence of Aspergillus in airway specimens (detected by culture, galactomannan antigen or specific PCR) remains to be fully understood. To decipher the relevance of the detection of Aspergillus, we performed a comprehensive review of all published cases of respiratory Aspergillus colonisation and IPA in COVID‐19 patients. The comparison of patients receiving or not antifungal treatment allowed us to highlight the most important criteria for the decision to treat. The comparison of surviving and non‐surviving patients made it possible to unveil criteria associated with mortality that should be taken into account in the treatment decision.

Impact of the SARS-CoV-2 Pandemic in Candidaemia, Invasive Aspergillosis and Antifungal Consumption in a Tertiary Hospital.

In addition to the increase in fungal infections that has been observed in the last few decades, it has been reported that severe clinical COVID-19 can increase the risk of invasive fungal infections. The main objective of this study was to evaluate if there had been an increase in candidaemia and invasive pulmonary aspergillosis (IPA) cases since the onset of the SARS-CoV-2 pandemic. Data were retrospectively collected from April 2019 to March 2021, from patients admitted to Consorcio Hospital General Universitario de Valencia (Spain). A total of 152 candidaemia cases (56 of which were due to Candida auris) and 108 possible IPA cases were detected. A great increase in candidaemia cases was produced during the first and the third epidemic waves of the SARS-CoV-2 pandemic (June 2020, and January 2021, respectively), while an increase in IPA cases was produced during the third wave. The 28-day mortality rates in patients affected by candidaemia and IPA increased in 2020 and 2021. C. auris has displaced the other Candida species, becoming the most isolated Candida species in blood cultures since the onset of the SARS-CoV-2 pandemic. Antifungal consumption increased in 2020 when compared to 2019, especially echinocandins, voriconazole and isavuconazole.

Diagnostic yield of a bronchoalveolar lavage fluid galactomannan assay in patients with negative serum galactomannan results suspected to have invasive pulmonary aspergillosis.

There are limited data in real clinical practice on the diagnostic value of a bronchoalveolar lavage (BAL) fluid galactomannan (GM) assay in patients with suspected invasive pulmonary aspergillosis (IPA) who had negative serum GM results. Thus, we investigated the diagnostic performance of a BAL GM assay in patients with negative serum GM assay results who were suspected to have IPA. This retrospective study was performed between May 2008 and April 2019 at a tertiary-care hospital in Seoul, South Korea. All patients with suspected IPA whose serum GM assays revealed negative results who sequentially underwent BAL were enrolled in this study. A total of 341 patients with suspected IPA including four cases of proven IPA, 38 cases of probable IPA, 107 cases of possible IPA and 192 patients without IPA were enrolled. Of these 341 patients, 107 (31%) with possible IPA were excluded from the final analysis. Of 42 patients with proven and probable IPA who had initial negative serum GM results, 24 (57%) had positive BAL GM results (n=24) or BAL fungal culture results (n=8). In addition, BAL revealed evidence of other opportunistic infections including Pneumocystis jirovecii pneumonia (14% [26/190]), cytomegalovirus (CMV) pneumonia (5% [9/188]) and respiratory viral pneumonia (6% [12/193]). Sequential BAL in patients with suspected IPA who had initial negative serum GM results provided additional diagnostic yield in approximately half of patients with evidence of another co-infection.

Dynamic monitor of CT scan within short interval in invasive pulmonary aspergillosis for nonneutropenic patients: a retrospective analysis in two centers

BackgroundIn nonneutropenic patients with underlying respiratory diseases (URD), invasive pulmonary aspergillosis (IPA) is a life-threatening disease. Yet establishing early diagnosis in those patients remains quite a challenge.MethodsA retrospective series of nonneutropenic patients with probable or proven IPA were reviewed from January 2014 to May 2018 in Department of Respiratory Medicine of two Chinese hospitals. Those patients were suspected of IPA and underwent lung computed tomography (CT) scans twice within 5–21 days. The items required for IPA diagnosis were assessed by their host factors, mycological findings and CT scans according to the European Organization for Research and Treatment of Cancer (EORTC) and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (MSG) criteria (EORTC/MSG criteria).ResultsTogether with the risk factors, mycological findings and nonspecific radiological signs on first CT, ten patients were suspected of IPA. With the appearance of cavities on second CT scan in the following days, all patients met the criteria of probable or possible IPA. Except one patient who refused antifungal treatment, nine patients received timely antifungal treatment and recovered well. One of the nine treated IPA cases was further confirmed by pathology, one was confirmed by biopsy.ConclusionsDynamic monitor of CT scan provided specific image evidences for IPA diagnosis. This novel finding might provide a noninvasive and efficient strategy in IPA diagnosis with URD.

Invasive Pulmonary Aspergillosis in Influenza and RSV: A Retrospective Cohort Study

Background: Recent studies in Europe and Asia have reported high incidences of invasive pulmonary aspergillosis (IPA) in patients with severe viral respiratory infections, even among immunocompetent individuals. Few large-scale studies have been done in the United States to understand the incidence of IPA in this population. Methods: Data was collected retrospectively on all patients with influenza or RSV infection admitted to the intensive care unit (ICU) at a single academic center in Chicago, IL between May 2008 and May 2018. IPA cases were defined using AspICU criteria. Baseline characteristics, demographics, disease severity, and outcomes were compared by Fisher exact and Mann-Whitney U tests for categorical and continuous variables. Findings: A total of 224 ICU patients with influenza and 153 with RSV met inclusion criteria over nine years. Among those, 7 (3·1%) patients with severe influenza and 8 (5·2%) with severe RSV were diagnosed with IPA based on the modified AspICU criteria. Among patients with severe influenza, history of hematopoietic stem cell transplantation was significantly associated with IPA, while history of hematopoietic stem cell transplantation, hematologic malignancy, and neutropenia were significantly associated with IPA in patients with severe RSV infection. Interpretation: The incidence of IPA complicating severe viral respiratory infection was significantly lower in our study compared to some European and Asian studies. Additionally, the majority of patients in our study had significant immunocompromising risk factors. Funding: This work was supported by the National Institutes of Health T32 Training grant [5T32AI095207] and data collection was supported by NCATS grant (UL1TR001422). Declaration of Interest: HHN and CV have no potential conflicts of interest to declare. MGI received research support, paid to Northwestern University, from AiCuris, Astellas, GlaxoSmithKline, Janssen and Shire; he is a paid consultant for Adagio, AlloVir, Celltrion, Cidara, Genentech, Roche, Janssen, Shionogi, Viracor Eurofins; he is also a paid member of DSMBs from CSL Behring, Janssen, Merck, SAB Biotherapeutics, Sequiris and Takeda; he receives royalty from UpToDate. Ethical Approval: This study was approved by the Northwestern Memorial Hospital Institutional Review Board office.

356. Clinical characteristics of critically ill patients with COVID-19 and invasive pulmonary aspergillosis: a case series from Mexico City

BackgroundCOVID-19, caused by SARS-CoV-2, has emerged as a global public health emergency and has been the main cause of intensive care admission during the pandemic. Invasive pulmonary aspergillosis (IPA) superinfection has been reported in case series of critically ill patients. Mexico has been widely affected by SARS-CoV-2. We present a case series of COVID-19-associated IPA at a teaching hospital in Mexico City.MethodsWe performed a retrospective analysis of COVID-19 patients admitted to the ABC Medical Center from March 13 to June 1, 2020. Only those with severe or critical COVID-19 were hospitalized. Patients with a diagnosis of putative IPA were analyzed. SARS-CoV-2 was diagnosed by Real-Time PCR from nasopharyngeal swabs. Aspergillus antigen testing in tracheal aspirate and serum was done with Aspergillus-specific galactomannoprotein (GP) ELISA (Euroimmun Medizinische Labordiagnostika).The study was approved by the hospital ethics committee.ResultsAmong the 47 admitted patients who required invasive mechanical ventilation (IMV), we identified seven (14.9%) cases of IPA. The mean age was 59.7 ± 17.8 years and five were male. All our patients had comorbidities, but none were under previous immunosuppressive treatment. All had critical COVID-19 pneumonia requiring IMV. All but one patient received corticosteroids, and five patients were treated with tocilizumab before IPA diagnosis. Putative IPA was diagnosed in six cases (86%) by a positive GP in tracheal aspirate, additionally in one of these, the tracheal aspirate culture also grew Aspergillus niger. The remaining one (14%) had a positive serum GP. The median time from COVID-19 to IPA diagnosis was 10 days. There were five bacterial co-infections, three with Pseudomonas aeruginosa, one with Stenotrophomonas maltophilia, and one with Mycobacterium tuberculosis. Six patients were treated with isavuconazole and one voriconazole. As of June 17, 2020, three patients had died, two patients had been discharged, and two were still in the intensive care unit receiving IMV.Aspergillus niger isolated from a tracheal aspirate of a critically-ill COVID-19 patient ConclusionCOVID-19-associated IPA had a lower prevalence than previously reported in other series. However, it appears to be linked to high mortality and could be associated with other bacterial coinfections.Disclosures All Authors: No reported disclosures

Proteome analysis of bronchoalveolar lavage fluids reveals host and fungal proteins highly expressed during invasive pulmonary aspergillosis in mice and humans

ABSTRACT Invasive pulmonary aspergillosis (IPA) is a severe infection that is difficult to diagnose due to the ubiquitous presence of fungal spores, the underlying diseases of risk patients, and limitations of currently available markers. In this study, we performed a comprehensive liquid chromatography tandem mass spectrometry (LC-MS/MS)-based identification of host and fungal proteins expressed during IPA in mice and humans. The proteomic analysis of bronchoalveolar lavage samples of individual IPA and control cases allowed the description of common host factors that had significantly increased abundance in both infected animals and IPA patients compared to their controls. Although increased levels of these individual host proteins might not be sufficient to distinguish bacterial from fungal infection, a combination of these markers might be beneficial to improve diagnosis. We also identified 16 fungal proteins that were specifically detected during infection and may be valuable candidates for biomarker evaluation.

Preliminary Attempt to Predict Risk of Invasive Pulmonary Aspergillosis in Patients with Influenza: Decision Trees May Help?

Invasive pulmonary aspergillosis (IPA) is typically considered a disease of immunocompromised patients, but, recently, many cases have been reported in patients without typical risk factors. The aim of our study is to develop a risk predictive model for IPA through machine learning techniques (decision trees) in patients with influenza. We conducted a retrospective observational study analyzing data regarding patients diagnosed with influenza hospitalized at the University Hospital “Umberto I” of Rome during the 2018-2019 season. We collected five IPA cases out of 77 influenza patients. Although the small sample size is a limit, the most vulnerable patients among the influenza-infected population seem to be those with evidence of lymphocytopenia and those that received corticosteroid therapy.