Serum Galactomannan Research Articles

Active screening of COVID-19-associated pulmonary aspergillosis with serum beta-glucan and endotracheal aspirates galactomannan and fungal culture.

Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution. To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol. We screened once per week, collecting endotracheal aspirates for fungal culture and galactomannan (GM) and serum for 1,3-ß-D-glucan (BG). In case of positivity (GM more than 4.5, platelia assay, and/or BG >7pg/ml, wako and/or positive fungal culture), second-level investigations were performed to pursue CAPA diagnosis according to ECMM/ISHAM criteria: bronchoalveolar lavage (BAL) fungal culture and GM, chest computed tomography (CT), serum GM. A total of 102 patients were screened (median age 64 years, range 39-79; 28 (27.4%) females). Twenty-two patients were diagnosed with CAPA (21%). 12 patients were positive for serum BG, 17 patients were positive for endotracheal aspirates GM and 27 patients were positive for endotracheal aspirates fungal culture. Thirty-two BALs were performed, and 26 patients underwent CT chest. Following the second level investigations 61% of the patients with positive screening tests were diagnosed with CAPA. Serum BG above 20 pg/ml or positive serum GM were always associated with typical CT chest signs of aspergillosis. Compared with 1 single positive test, having 2 positive screening test was significantly more associated with CAPA diagnosis (p= .0004). Active CAPA screening with serum 1,3-ß-D-glucan and endotracheal aspirates galactomannan and fungal cultures and consequent second level investigations led to high number of CAPA diagnosis. Combining more positive fungal biomarkers was more predictive of CAPA diagnosis.

Aspergillus pleural empyema in a chronic smoker – A case report and review of literature

Aspergillus species are ubiquitous saprophytic fungi that are present in the air, water, soil, and decaying vegetables. Clinical features of Aspergillus infection largely depend on the interplay between the fungi and the host immune status. We present a case of a chronic smoker with shortness of breath who was found to have diffuse bronchiectatic changes and empyema of the right lung. Emphysema was also noticed in the left lung. Rare Aspergillus fumigatus was identified in the pleural fluid, while the acid-fast stain and bacterial cultures were negative. The patient's serum Aspergillus fumigatus IgG antibody and galactomannan antigen were negative; however, the pleural galactomannan antigen was elevated. He was treated with video-assisted thoracoscopic surgery (VATS) and partial decortication of the right lung, along with intravenous voriconazole. Despite aggressive therapeutic measures, he died after a prolonged hospital stay. Aspergillus pleural empyema is rare but can be fatal; however, it is not included in the classification for pulmonary aspergillosis. Clinicians should be vigilant to evaluate for fungal empyema in patients with chronic obstructive pulmonary diseases, even without profound immunosuppression.

Clinical performance of metagenomic next-generation sequencing for the rapid diagnosis of talaromycosis in HIV-infected patients.

Talaromycosis is an invasive endemic mycosis caused by the dimorphic fungus Talaromyces marneffei (T. marneffei, TM). It mainly affects immunodeficient patients, especially HIV-infected individuals, which causes significant morbidity and mortality. Culture-based diagnosis takes a long turnaround time with low sensitivity, leading to treatment delay. In this study, we aimed to evaluate the performance of Metagenomic Next-Generation Sequencing (mNGS) for the rapid diagnosis of talaromycosis in HIV-infected patients. Retrospectively analysis was conducted in HIV-infected cases at Changsha First Hospital (China) from January 2021 to March 2022. Patients who underwent routine microbiological examination and mNGS testing in parallel were enrolled. The clinical final diagnosis was used as a reference standard, and cases were classified into the TM group (60 cases) and the non-TM group (148 cases). The clinical performances of mNGS were compared with culture and serum Galactomannan (GM). The mixed infections detected by mNGS were analyzed. The impact of mNGS detection on treatment was also investigated. The sensitivity of mNGS test reached 98.3% (95% CI, 89.8-99.9), which was significantly higher than culture (66.7% [95% CI, 53.2-77.9], P < 0.001) and serum GM (83.3% [95% CI, 71.0-91.2], P < 0.05). The specificity of 98.6% (95% CI, 94.7-99.7) was similar to culture (100.0% [95% CI, 96.8-100.0], P = 0.156), and superior to serum GM (91.9% [95% CI, 85.9-95.5], P < 0.05). In bronchoalveolar lavage fluid (BALF) samples, the positive rate of mNGS was 97.6%, which was significantly higher than culture (28.6%, P <0.001). mNGS has excellent performance in the identification of mixed infection in TM group patients. Cytomegalovirus, Epstein-Barr virus and Pneumocystis jirovecii were the most common concurrent pathogens. In summary, 60.0% (36/60) patients were added or adjusted to antimicrobial therapy after mNGS test. mNGS is a powerful technique with high specificity and sensitivity for the rapid diagnosis of talaromycosis. mNGS of BALF samples may be a good option for early identification of T. marneffei in HIV-infected individuals with manifestations of infection. Moreover, mNGS shows excellent performance in mixed infection, which benefits timely treatment and potential mortality reduction.

Potential diagnostic role of galactomannan and β-D-glucan in occupational asthmatics in wheat mills

Occupational asthma is defined as variable airway obstruction due to exposure to a specific substance in the workplace environment. The aim of the study was to find out the frequency of occupational asthma in wheat mill workers and to explore the role of fungi biomarkers (galactomannan (GM) and β-D-glucan (βDG)) in occupational asthma. Subjects and methods: Assessment of fungi in air was done. Spirometric function of workers (n=120) were assessed during diurnal (before and 15 minutes after inhalation of salbutamol) and nocturnal time. Blood samples were analyzed to measure serum GM and βDG and allergen specific immunoglobulin E. The workers were asked about asthma symptoms. Results and conclusion: A significant proportion of workers had occupational asthma (25%) and only four workers (3.3%) had non-occupational asthma (excluded from the study). The rest were normal (86 workers). Penicillium and Aspergillus were the only species found in the air environment. Mean GM concentration (GM-c) was significantly higher among occupational asthmatics than normal workers. The estimated risk of occupational asthma (Odds ratio) was 13.3 times higher among workers with high GM-c (>1 pg/ml). Ln (GM) was the only significant predictor of PEFR variability. GM has a potential diagnostic role in occupational asthma due to fungal exposure among wheat mill workers. βDG did not have a role in occupational asthma. We recommend that wheat mill flour workers should do periodic spirometric functions and serum GM every 6 - 12 months for early diagnosis and control of occupational asthma.

TUMOR NECROSIS FACTOR (TNF) ALPHA INHIBITORS, ASPERGILLOSIS, AND GALACTOMANNAN: THE PERILS OF BEING MISLED BY AN INSENSITIVE TEST

TUMOR NECROSIS FACTOR (TNF) ALPHA INHIBITORS, ASPERGILLOSIS, AND GALACTOMANNAN: THE PERILS OF BEING MISLED BY AN INSENSITIVE TEST

AN UNCOMMON INFECTIOUS IMPOSTER OF LUNG CANCER: A CASE OF ASPERGILLUS NODULES

AN UNCOMMON INFECTIOUS IMPOSTER OF LUNG CANCER: A CASE OF ASPERGILLUS NODULES

Study of Microbial Infections and Some Immunological Parameters among Covid-19 in ICU Patients in Najaf Governorate, Iraq.

The present study aimed to investigate some microbial infections and immunological parameters associated with Covid-19 patients admitted to the intensive care unit (ICU) of Al-Amal Specialized Hospital in AL-Najaf Governorate during February and March 2021. The study included 50 patients who were assigned to two groups: 20 patients aged ≤70 years and 30 patients aged ≥70 years. The method of microbial culture was adopted to isolate bacteria and yeasts by collecting sputum specimens and oral swabs from patients and cultivating them on diagnostic media and then confirming the diagnosis by Vitek. Moreover, serum samples were collected from patients' blood to diagnose fungal infections. Thereafter, some immunological criteria were assessed, including Covid-19 diagnosis by measuring Immunoglobulin M (IgM) and IgG, as well as examining the concentration of cytokines (Interleukin 6 (IL-6) and IF ) using the enzyme-linked immunosorbent assay (ELISA) method. The results demonstrated that bacterial species Streptococcus pneumonia (n=5; 25%), Haemophilus Influenzae (n=7; 35%), and Moraxella catarrhalis (n=3; 15%) were isolated from the first group of patients (≤70 years). The recorded data pointed out that Streptococcus pneumonia (n=10; 33.3%), Streptococcus pyogenes (n=5; 16.6%), Streptococcus viridans (n=1; 3.3%), Haemophilus Influenzae (n=6; 20%), Mycobacterium tuberculosis (n=2; 6.6%), and Pseudomonas aeruginosa (n=2; 6.6%) were the isolated and identified microorganisms in the second age group (≥ 70 years). The results revealed that the isolated yeast from the first age group was Candida albicans (n=5; 25%) and Candida glabrata (n=3; 10%), while in the second age group, 1 (3.3%) Candida albicans was isolated. The results of this study proved that 30% and 10% of patients in the first and second age groups had invasive pulmonary aspergillosis co-infection by detecting Galactomannan (GM) in the blood serum (1.05±0.59, 1.25±0.38), respectively. The results indicated that IgM and IgG levels in the serum of patients in the first age group were 11.42±6.82 and 0.47±6.82, respectively. Moreover, the levels of IgM and IgG in the second age group were 14.84±9.21 and 0.12±0.11, respectively. Furthermore, IFɤ and IL6 levels were 98.37±65.70, and 146.12±46.35 in the first group, while IFɤ and IL6 were obtained at 110.69±47.60 and 133.28±116.94 in the second group, respectively. Elderly patients with severe COVID-19 are more frequently admitted to ICUs since the proportion of severe cases and comorbidities caused by a weakened immune system is higher among this age group. Secondary bacterial infections can also occur, especially Gram-negative bacteria which are among the most significant public health problems worldwide. Moroever, aspergillosis may infect patients hospitalized with COVID-19 and lead to death.

AML-197 Incidence of Infectious Lung Disease in Neutropenic Patients

Immunosuppression caused by hematologic malignancies can affect all cell lines, but profound neutropenia is the main risk factor. The most common infection is pneumonia. More than 60% of neutropenic patients develop a lung infection. These infections develop in 13-31% of patients during induction chemotherapy for acute myeloid leukemia (AML). They are associated with a significantly higher mortality rate than other infectious diseases. Deduce the incidence of infectious lung disease in our neutropenic patients. This is an observational, descriptive, and prospective study carried out in the Department of Hematology and Pediatric Oncology 20 August of Casablanca, spread over a period of 10 months, from 01 May 2019 to 29 February 2020. It focuses on adult patients over 18 years of age with neutropenia (a PNN count < 2×109/L) hospitalized in the protected unit (AML and aplastic anemia) and the transplant unit, who presented an episode of infectious lung disease during the study period. We determined the incidence and studied the clinical and radiological presentation, the diagnostic steps to obtain biological and microbiological documentation, and the final evolution of these infectious episodes. Out of a total of 235 admissions, 50 episodes of infectious lung disease were identified in 49 patients, for an overall incidence of 21.28%. The most frequent phase of treatment was that of Induction in AML. Thoracic CT was performed in all patients. Bronchoalveolar lavage was performed over 9 episodes. The results were positive in 44.5% of episodes. Serum galactomannan antigenemia assay was performed in 94% of cases, it was positive in 22 (46%). The GeneXpert technique was performed in six episodes (12%), with one positive result. The probable fungal infection was the cause of these infections in 58% of cases. Bacterial pneumopathy was present in 22% of episodes. Pulmonary tuberculosis was diagnosed in only one patient. Pneumocystis was suspected in 4 episodes and viral infection was suspected in 3 episodes. The evolution was favorable in 52% of the cases. The review of the literature has shown that the establishment of an etiological diagnosis is not always possible during these infections, the treatment is essentially empirical, and with a terrible prognosis.

P412 QuicGM Aspergillus Galactomannan Ag lateral flow assay as a practical aid to diagnose invasive Aspergillosis in high-risk hematology patients

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMBackgroundEarly diagnosis of invasive aspergillosis (IA) is an important factor to improve survival, but it remains challenging. QuicGM Aspergillus Galactomannan Ag Lateral Flow Assay (LFA) is based on a fluorescence immunochromatography test using a monoclonal antibody to identify Aspergillus galactomannan antigen in serum and bronchoalveolar lavage fluid.MethodsIn this study, we analyzed the diagnostic performance of QuicGM in 120 serum samples of high-risk hematology patients [41 cases of proven (n = 4) and probable (n = 37) IA and 79 equally high-risk controls] and compared it to performance of the galactomannan (GM) [Platelia Aspergillus enzyme immunoassay (ELISA) (Bio-Rad, Marnes-la-Coquette, France)]. Probable cases defined by a positive Biorad GM in serum were also included in the cohort.ResultsUsing the same cut-off of 0.5, QuicGM was positive in 22 cases versus GM in 21 cases. However, QuicGM was false positive in 11 controls with GM only in 1 control. These false positive samples remained positive upon repeated testing with the QuicGM. The test results of QuicGM and GM correlated well with a Spearman's correlation coefficient of 0.80 (P <.001). McNemar test showed no significant difference between both tests (P = 1) and Cohen's kappa coefficient was 0.65 (CI 0.49-0.81), suggesting a substantial strength of agreement.QuicGM sensitivity (using 0.5 cutoff) was 54% versus 51% for GM. Specificity was 86% for QuicGM versus 99% for GM. Positive predictive value (PPV) was only 67% for QuicGM versus 95% for GM. Combining GM and QuicGM in serum increased sensitivity to 59%. Youden index of QuicGM in the cohort was 0.39. Using this cutoff, sensitivity was 66% and specificity was 80%. When using a higher cutoff of 0.6 for the QuicGM, specificity increased to 94% and PPV to 78%, at the cost of a decrease in sensitivity to 44%.DiscussionIncluding probable cases defined by a positive Biorad GM in serum could have led to a bias in favor of the GM.With the cutoff suggested by the company, there was a notable decrease in specificity and PPV for the QuicGM. The need to adjust this cut-off must be questioned. With the implementation of LFAs in the EORTC-MSGERG criteria, one usually strives for the same cutoff of 0.5, to assure a practical approach. However, we must remain thoughtful about slight differences in these tests. They all have their own IgG and IgM built. Caution is needed more in the setting of diagnosis than in screening.More knowledge must be obtained regarding how different hospital laboratories have implemented the LFAs.ConclusionDiagnostic performances of QuicGM and Biorad GM correlate well.Further research is necessary regarding the optimal cutoff index.

P447 Galactomannan lateral flow assay for the diagnosis of invasive Aspergillosis among clinically suspected patients in tertiary care center, Jodhpur, Rajasthan

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM IntroductionInvasive aspergillosis is one of the potentially life-threatening diseases in immunocompromised patients. Early diagnosis and prompt treatment improve patient survival. The gold standard method—conventional microscopy and culture have low sensitivity and a long turnaround time. Serum Galactomannan (GM), a polysaccharide that forms a major component of Aspergillus cell wall and is released by the fungus during invasive growth is established as a reliable biomarker, which is available as Enzyme Linked Immunoassay (ELISA). The limitations of ELISA are high cost, expertise, and difficulty in assay standardization. To overcome these limitations, a qualitative Galactomannan Lateral Flow Assay (GM-LFA) a sandwich immunochromatographic test, recently approved by European CE, is evaluated in our study.ObjectiveTo establish the diagnosis of Invasive Aspergillosis according to EORTC/MSGERC Definitions of Invasive Fungal Diseases 2021 guidelines and comparison of GM-LFA with conventional microscopy and culture.MethodWe performed a retrospective study from October 2021 to March 2022 on serum and bronchoalveolar lavage fluid (BAL) samples. GM-LFA (IMMY sōna Aspergillus Galactomannan LFA) was performed and the results are read after 10 mins with a cube reader according to the manufacturer’s instructions and compared with conventional microscopy and culture.ResultDuring the 6 months study period, 185 samples (14 BAL and 171 Serum) were collected from 148 patients. A total of 17/185 (9.18%) samples from 16 patients were positive by GM-LFA, of those 5 (29.41%) are BAL, and 12 (70.58%) are serum samples. One patient tested positive for Galactomannan on both BAL and serum.Among Assay positive samples, 3/17 (17.64%) samples were positive by microscopy and culture, which grew 2 Aspergillus fumigatus and 1 Aspergillus niger.Treatment details of 5 patients could be traced, of which 4 patients improved clinically and radiologically after Inj. voriconazole and 1 patient died before starting treatment.According to EORTC/MSGERC Definitions of Invasive Fungal Diseases 2021 guidelines, 17 patients belong to the proven and probable Invasive aspergillosis category, in which 16 patients were GM-LFA-positive and the remaining 131 patients had no evidence of invasive aspergillosis disease.ConclusionGM-LFA is a cost-effective, easy, convenient, and rapid procedure. We recommend its use for the diagnosis of invasive Aspergillosis in routine healthcare settings, especially where GM-ELISA is not available or affordable.

P169 Systemic Pythiosis: presumably, the first human case in India

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectivesThis is the first human case of systemic disease due to Pythium insidiosum reported from India. The case highlights difficulty in diagnosis and management.MethodsA 44-year-old male patient had a peri-esophageal and peri-gastric inflammatory lesion which showed inflammation along with sparsely septate hyphae (Fig. 1), and partially responded to voriconazole (VCZ). After 1.5 years, he developed a massive liver lesion (Fig. 2), and hepatic venous thrombosis which was refractory despite restarting therapy with posaconazole (PCZ). As a desperate measure, surgical excision of the large liver lesion was undertaken.ResultsSerum BDG was positive and Serum Galactomannan was negative. There was no tidy explanation for the insidious clinical course of the illness over 1.5 years, partial response to VCZ for the esophageal lesion and inadequate response of the subsequent lesion to PCZ. The liver biopsy specimen showed a flat, feathery growth on SDA which was identified at PGI, Chandigarh by ITS as P. insidiosum. P. insidiosum and additionally Rhizopus microsporus were identified by molecular sequencing from the surgical specimen as well. The patient succumbed to carbapenem-resistant Klebsiella bacteremia in the postoperative stage.ConclusionThe case underscores the insidious course of systemic pythiosis, diagnostic, and management challenges.

P172 First report of Aspergillus tamarii producing influenza associated invasive pulmonary Aspergillosis

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM ObjectiveMultiple infections can occur after 2009, pandemic influenza, including fungal and bacterial infections, but data from India are limited. To our knowledge, this is the first reported case of influenza-associated invasive pulmonary aspergillosis (IAPA), caused by Aspergillus tamarii, after infection with pandemic (H1N1) 2009 which was preceded by COVID-19, 20 months before.Methods and ResultsA 33-year-old male, known asthmatic, had been hospitalized elsewhere in August 2020 with COVID-19 pneumonia for 50 days and had been on mechanical ventilation for 37 days. He had no residual respiratory symptoms 3 months after recovery from COVID-19. He was admitted to Jupiter Hospital in April 2022 with fever, cough, and dyspnea for 8 days, which developed after a cold bath in a temple. HRCT (chest) showed ground glass opacities (GGOs), crazy paving, nodules, and traction bronchiectasis. Review of previous HRCT showed that only GGOs were present (Fig. 1).At admission, the nasopharyngeal swab was positive for pandemic (H1N1) 2009 in the filmarray respiratory panel and no other pathogen was detected. He was treated with oseltamivir. Expectorated sputum examination showed a heavy load of thin septate hyphae, with acute angle branching, resembling Aspergilllus species (Fig. 2). Serum galactomannan was positive (1.8). Based on these features he was diagnosed as a case of probable IAPA and initiated posaconazole (PCZ) treatment. Sputum fungal culture was positive and was identified by MALDI TOF MS as A. tamarii. A. tamarii has been rarely encountered as a human pathogen. Case reports of its involvement in eyelid infection, keratitis, invasive sinonasal infection, and onychomycosis exist. Sensititre MICs were 0.0625 mcg/ml, 0.125 mcg/ml, 0.0625 mcg/ml, and 0.125 mcg/mL for itraconazole, voriconazole, PCZ, and for isavuconazole (ISVCZ) respectively.The usually obtained PCZ trough level with standard dose is 1.2 mg/l which generates AUC of 200R. The usually obtained ISVC) trough level with standard dose is 3 mg/l which generates AUC of 100R. The PKPD index, AUC/MIC of 100, is needed with both these azoles for a therapeutic effectR. Therefore, it would be possible to treat this infection with any of these azoles.PCZ was continued in view of the easy availability of therapeutic drug monitoring (TDM) to assure adequate drug exposure, lower cost, and clinical improvement which had already occurred.ConclusionAn infection due to a rare Aspergillus species needs correct identification, MIC determination, and PKPD consideration for appropriate drug selection and management.

P170 Life threatening hemoptysis in COVID-19 associated Pulmonary Aspergillosis (CAPA)

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMObjectiveWe report a case of large pulmonary mycotic aneurysms with massive hemorrhage as an unusual complication of CAPA which required vascular radiological interventions along with appropriate antifungal treatment.Method and ResultsA 71-year-old female patient had COVID-19 and was admitted elsewhere and she received steroids, aspirin, antibiotics, and fluconazole. Cough, dyspnea, and hemoptysis started 3 weeks later which markedly worsened over 4 days, requiring emergency hospitalization due to shock, and she received a large number of packed RBCs. The chest CT scan revealed two large nodular opacities with central breakdown and CT pulmonary angiography revealed large mycotic aneurysms within the nodular opacities (Fig. 1).The important task at the moment of presentation was pulmonary artery embolization to arrest hemoptysis; which took precedence over the diagnosis and treatment of the likely infectious process. Both aneurysms were embolized using coils and vascular plugs resulting in their obliteration.Common causes of such nodules with central necrotic cavitation and formation of pseudoaneurysms are angioinvasive molds like Aspergillus and Mucorales. In the post-COVID-19 and post steroid setting in India, invasive Mucormycosis (IM) is thought to be more common than invasive Aspergillosis (IA). A mixed infection with these molds appears to be present in about 15% of the cases. Absence of DM or hyperglycemia was somewhat against a diagnosis of Mucormycosis. TB was considered less likely due to the imaging features and Nocardia was considered less likely due to the tempo of the illness and the severity of hemoptysis.Since the clinical distinction between Aspergillosis and Mucormycosis was not possible and posaconazole can be potentially useful for both, it was chosen for treatment in preference to voriconazole. Both amphotericin B and isavuconazole were in short supply at that time. Posaconazole was used for the patient intravenously followed by gastroresistant tablets. Expectorated sputum revealed narrow, septate, acute angle branching fungal hyphae. Therapeutic drug monitoring was used later to assure an adequate drug exposure. Serum galactomannan and BDG reports were received soon after and were 2.49 ODI (Optical density Index) and >523pg/ml respectively. The mold grew in culture as shown in and was identified by morphological features and by MALDI TOF MS as Aspergillus fumigatus (Fig. 2). Sensititre MIC to posaconazole was found to be 0.12 which is considered in the susceptible range.Despite these findings indicating IA, posaconazole was not replaced by voriconazole as IM could not be ruled out as part of a mixed infection. The patient showed clinical improvement, had no further hemoptysis, serum galactomannan turned negative and CT showed obliteration of the aneurysms.ConclusionPosaconazole and isavuconazole may indeed emerge as good contemporary choices over voriconazole for IA and over amphotericin B for IM.This case adds to the clinical experience of using medical treatment with posaconazole as the sole drug and not undertaking surgery in cases such as these, due to certain extenuating circumstances.

P409 Study of epidemiology, risk factors and antifungal sensitivity pattern of fungal pneumonia in critically ill cirrhotics

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PM ObjectivesLiver cirrhosis causes immune dysregulation and increased susceptibility to fungal infections. We studied the epidemiology and risk factors, and compared the rapid diagnostic methods and biomarkers for fungal pneumonia in critically ill cirrhotics.MethodsSingle-center, prospective cohort study of 100 critically ill cirrhotics with fungal pneumonia between January to September 2021. Comparative analysis was done for culture, realtime PCR and biomarkers, bronchoalveolar lavage and serum Galactomannan, and serum procalcitonin measured on days 1, 3, and 7. The final outcome considered was mortality within 1 month after diagnosis or discharge.Results Aspergillus flavus was the most common species (70/100,70%). Risk factors were, neutropenia (P .03), steroids prior to ICU admission (P .02), prolonged hospitalizations ˃21 days (P .05), and culture positivity was 80%. The culture was not inferior to realtime PCR for the diagnosis of fungal pneumonia. BAL Galactomannan was an early prognostic marker with a median rise above ˃ 3.5 index value. The Median PCT level was higher from day 1in the fungal pneumonia non-survivor group (3.29 vs. 0.8 ng/ml) with higher 30-day mortality (72%). Higher PCT was associated with bacterial co-infection (48%), antibiotic (74%), antifungal therapy, and renal failure and mortality.ConclusionFungal pneumonia complicates cirrhotics with neutropenia, prolonged hospitalization, and steroids as risk factors. Aspergillus flavus predominate in consensus with Asian epidemiology. Culture methods are reliable and a combination of molecular tests with BAL Galactomannan is useful for rapid diagnosis. Serum PCT is raised in patients with fungal pneumonia and is associated with higher mortality. In our study the baseline PCT at admission to ICU was higher in the non-survivor group, and levels on D3 and D7 were persistently higher. High serum procalcitonin level is an independent prognostic biomarker of mortality risk in fungal pneumonia.

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.

P469 Feline aspergillosis caused by Aspergillus candidus: A case report

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMAspergillosis is an emerging mycosis that can occur in apparently healthy animals under environmental stress or immune-compromised condition. In cats, the clinical forms described are sinonasal, synoorbital, and, less frequently, invasive and disseminated forms.Feline aspergillosis is caused mainly by cryptic species of Aspergillus closely related to Aspergillus fumigatus. It is rare to recover species such as A. candidus, an endophytic fungus, opportunistic pathogen, and contaminant of cereals, nuts, and flour. It is described to cause allergic alveolitis or asthma, mycotoxicosis, and other related diseases. Mycelial fragments, inhaled spores, and substances such as terpenoids, flavones, and indoles in the lungs could be involved in the underlying pathogenesis.This presentation aims to describe a clinical case of feline pneumonia caused by A. candidus.Clinical caseWe present the clinical case of a common European breed feline of ∼ 7 years of age. The cat was rescued from the streets of an urban area in Buenos Aires and examined in April 2021. The feline suffered from mild hyperthermia, 39.4°C, had pale to slightly purple mucous membranes, cachexia, dehydration, dyspnea (abdominal respiration), tachycardia, and a large number of parasites. There were no nasal discharge, cough, or skin lesions. A hemogram with a blood biochemistry profile showed no significant alterations. Chest X-rays showed a pattern compatible with severe miliary pneumonia. A bronchoalveolar lavage (BAL) was performed for cytology and microbiological culture; direct examination showed nucleated superficial epithelial cells without atypia, few macrophages, no leukocytes, and gram-positive cocci, while ZN and mycological direct examination were negative. Treatment with doxycycline 10 mg/k every 12 h and dexamethasone was indicated. Flea treatment and control were conducted every 72 h. During the following consultations, the cat continued tachypnoeic and showed increased vesicular murmur with rales and cough. Corticosteroids (Fluticasone propionate 125 mg) were given every 12 h intranasal. Oral parasitization was performed due to the presence of Dipylidium caninum in feces. After 7 days of incubation, white cottony colonies phenotypically identified as Aspergillus grew on Sabouraud dextrose agar. Even though serum galactomannan GM (Platelia Aspergillus EIA BIORAD®) is useful as a biomarker in humans with OD >0.5 positive for invasive aspergillosis, it was used in this case and the result was OD 0.75. Antifungal treatment was started with itraconazole orally at 5 mg/kg/d. A mycobacterial culture was negative.The isolate was identified by partial sequencing of the calmodulin gene CaM as A. candidus.The feline showed a remarkable recovery. After 35 days from the start of the treatment, the final consultation showed a decrease in the pattern of military pneumonia through radiological images and an absence of any evident respiratory symptoms.ConclusionWe describe a fungal infection in a cat caused by an unusual species of Aspergillus. Moreover, this clinical case was proved to be pneumonia. Given this, it is important to consider this species as an emerging pathogen in cats.

P263 Invasive Pulmonary Aspergillosis (IPA) Among Non-Intubated COVID-19 Patients—a New Age Fungal Storm

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PM IntroductionCOVID-19 patients are at higher risk for the development of secondary infections, especially fungal due to multiple risk factors associated with COVID illness and its management. COVID-associated pulmonary aspergillosis (CAPA) is a new clinical entity that is contributing to high morbidity and mortality among immunocompetent COVID-19 patients. Lack of adequate published literature, absence of typical host factors, and lack of specific diagnostic criteria and management algorithms add to the difficulty in early diagnosis and treatment initiation. The scant available data is on CAPA among intubated patients, however, there are no data on CAPA in non-intubated COVID-19 patients.ObjectiveThe aim of our study was to assess the occurrence of IPA among non-intubated COVID-19 patients and its correlation with their demographic profile, risk factors, morbidity, and outcome.MethodsThis observational study included 24 non-intubated CAPA patients and 72 controls (1:3 randomly selected age and sex matched) at our hospital between April-June 2021. CAPA cases were defined as per modified-AspICU criteria. Demographic characteristics, risk factors, treatment, factors contributing to morbidity, and outcomes were evaluated. Descriptive statistics were reported as mean ± SD, median, number, and percentages. The proportion of CAPA was reported as frequencies and percentages. Clinical characteristics were compared between CAPA and control using Chi-squared, independent t-test and Mann-Whitney U test as appropriate. Association of CAPA with mortality was performed using Fisher's exact test. Logistic regression was performed to assess the factors associated with CAPA. P-value ˂5% was considered statistically significant. All analyses were performed using SPSS 25.0.ResultsA total of 4058 COVID patients were admitted during the study period. Respiratory samples of 26 patients yielded Aspergillus species. Two patients were excluded as colonizers based on modified AspICU criteria. In all, 24 CAPA cases 72 controls were studied for all the variables. CAPA occurrence was 0.59% among non-intubated COVID-19 patients (24/4058).Both the groups had a male preponderance (75% CAPA, 80% control), the median age was 52.8 ± 14.3. Demographic data and risk factors were comparable. There were no significant differences in lab parameters between the groups. Association of COVID severity and development of CAPA was not statistically significant (mod:OR 2.25, 95% CI, P-value .48; severe:OR 6.65, 95% CI, P-value .08). Significant associations between the cases and controls included, treatment with a higher dose and longer duration of steroids with development of CAPA (dose:OR 1.009, 95% CI, P-value .002; duration:OR 1.09, 95% CI, P-value .006), longer hospital stay (median of 18.4±10days (P-value .008). All-cause mortality was 16.7% in CAPA group (P-value <.0001).Between CAPA non-survivors and survivors, Serum galactomannan levels (P-value .03), duration of hospital stay (P-value .042), dose and duration of systemic corticosteroid (P-value .001), and duration of oxygen requirement (P-value .05) were found to be statistically significant.ConclusionCAPA is an emerging complication with high morbidity and mortality among immunocompetent COVID-19 patients that requires a high index of clinical suspicion. A standard diagnostic criteria and management protocol for early identification and treatment initiation is the need of the hour. Role of steroids in the development of CAPA and the role of galactomannan in diagnosis and prognosis of CAPA needs to be further investigated.

P203 Chronic pulmonary aspergillosis (CPA) in post tuberculosis sequele— aclinical experience from tertiary care

Poster session 2, September 22, 2022, 12:30 PM - 1:30 PMIntroductionChronic pulmonary aspergillosis (CPA) is a spectrum of illnesses clinically presenting as a persistent cough, dyspnea, hemoptysis, fatigue, and weight loss and radiologically can range from single aspergilloma, Aspergillus nodule, or chronic cavitary pulmonary aspergillosis (CCPA) which can progress to chronic fibrosing pulmonary aspergillosis if left untreated.1 CPA has high morbidity, burden in India estimated to be in a 5-year prevalence of 24/100 000.2 The commonly used criteria for diagnosing CPA include cough or hemoptysis for 1 month, raised Aspergillus-specific IgG, absence of positive GeneXpert test for Mycobacterium tuberculosis and either paracavitary fibrosis or a fungal ball on imaging of the thorax or progressive cavitation (either new cavitation or deterioration of pre-existing cavitation) on serial chest radiographs. Pulmonary tuberculosis (PTB) is the important predisposing risk factor for CPA,3 India being an endemic country, incidence of CPA may be underestimated or it may be misdiagnosed as smear-negative tuberculosis. Microbiologically, diagnosis by direct confirmation of Aspergillus spp infection (microscopy or culture from respiratory samples) may not be always positive, in such a scenario the immune response to Aspergillus spp. by measuring Aspergillus specific Immunoglobulin Ig G in clinically suspected cases may be used for diagnosis of CPA.MethodThis is a cross-sectional conducted in a tertiary care hospital, New Delhi, India. The patients with previous history of pulmonary tuberculosis who presented with symptoms of cough, hemoptysis, fever, shortness of breath, chest pain, and weight loss of ˃12-week duration were enrolled in the study. Relevant investigations including blood tests, chest imaging, sputum examination for bacterial infections, fungal (KOH mount), and tuberculosis (AFB smear, CBNAAT, mycobacterial cultures) were done. Microbiological evidence included a positive Aspergillus-specific IgG (cut off >8 units/ml) or positive serum galactomannan index (GMI) (cut off >1 according to EORTC/MSG guidelines) or KOH mount on sputum showing branching hyaline septate hyphae morphologically suggestive of Aspergillus spp. Patients who were diagnosed with CPA according to criteria were treated and followed up.ResultsA total of 15 patients were screened in the study, 4 patients who had concurrently detected pulmonary tuberculosis detected by Genexpert, were excluded from the study. Majority of patients presented with complaints of recurrent episodes of cough and hemoptysis. Imaging features included cavitation, bronchiectasis, pleural thickening, and fungal ball. Sputum microscopy for fungal elements was positive only in 10 patients. The serum Aspergillus Ig G (values ranged from 19.8-200 u/mL) was raised in all patients while serum GMI above cut-off was present in only 5 patients. All confirmed CPA patients were managed with voriconazole for 4 months. Following 4 months of treatment, all patients had favorable outcomes in terms of radiological improvement and clinical cure.ConclusionCPA is an underestimated post-PTB sequel and should be considered as differentials in patients with respiratory symptoms in post TB patients. Aspergillus Ig G and chest imaging are recommended as initial diagnostic tools for diagnosing CPA.Sources:Denning DW, Cadranel J, Beigelman-Aubry C et al. European Society for Clinical Microbiology and Infectious Diseases and European Respiratory Society. Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management. Eur Respir J. 2016; 47(1): 45-68.Agarwal R, Denning DW, Chakrabarti A. Estimation of the burden of chronic and allergic pulmonary aspergillosis in India. PLoS One. 2014; 9(12): e114745.Page ID, Byanyima R, Hosmane S et al. Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation. Eur Respir J. 2019; 53: 1801184

P408 Evaluation of fungal serum biomarkers in the diagnosis and for monitoring patients with post tuberculosis chronic pulmonary aspergillosis

Poster session 3, September 23, 2022, 12:30 PM - 1:30 PMObjectivesThe evaluation of serum β-D-glucan, galactomannan, and Aspergillus fumigatus specific IgG in the diagnosis and clinical management of patients with chronic pulmonary aspergillosis.MethodsConsecutive patients with a past history of pulmonary tuberculosis (PTB) with clinical suspicion of chronic pulmonary aspergillosis (CPA) attending the outpatient services of PGIMER, Chandigarh were included from August 2019 to August 2021, and CPA was defined as described by Denning et al. including both radiological and mycological evidence. Age and sex-matched post-PTB individuals selected from a population attending the chest clinic were enrolled as controls. Serum samples were obtained from all participants and testing for serum β-D-glucan (Fungitell, CapeCod), galactomannan (Platelia, BioRad) and Aspergillus fumigatus specific IgG (ImmunoCAP, Phadia) was performed as per manufacturer's instructions.ResultsA total of 105 post-TB patients with CPA and 11 controls were enrolled. Aspergillus fumigatus (n = 8) was the most commonly isolated species, followed by A. flavus (n = 4), and A. niger (n = 2). The mean A. fumigatus specific IgG levels, serum galactomannan index and BDG levels were higher among CPA cases vs. controls at 101.4 mgA/l vs. 11.8 mgA/l, P-value: .0001; 0.73 vs. 0.35, P-value: .3134; and 133.7 pg/ml vs. 32.37 pg/ml, P-value: .012, respectively (Figs. 1a, b, c). The serum BDG had an area under curve 0.834 ± 0.044 (95% CI: 0.748-0.920) on the ROC curve with a sensitivity of 57.1% and specificity of 100% at the kit cut-off of 80 pg/ml (Fig. 2a). Comparison between CPA patients with multiple (n = 38) versus single lobe (n = 67) involvement showed comparable A. fumigatus specific IgG levels (112.3 vs. 93.8; P-value: .133 respectively) while galactomannan index and BDG levels were higher in cases with multiple vs. single lobe involvement (0.94 vs. 0.57, P-value: .117), and (174.3 vs. 105.3, P-value: .0071), respectively (Fig. 1d, e, f). There was a significant association of BDG value with the severity of dyspnea (P-value: .002) and a trend of higher A. fumigatus specific IgG was also seen to correlate with the severity of dyspnea (Fig. 2b and 2c).ConclusionBDG assay can serve as an adjunct in the diagnosis of patients with CPA. An association of higher levels of BDG with multiple lobe involvement and severe dyspnea could be due to more extensive tissue damage associated with a greater release of antigen in circulation during progressive disease. More studies with a larger number of control samples, preferably with multi-center coordination can further improve our understanding of this test's applicability in routine practice.

Invasive Fungal Disease in Patients with Myeloid Malignancies: A Retrospective Cohort Study of a Diagnostic-Driven Care Pathway Withholding Mould-Active Prophylaxis

Objectives: Patients receiving remission induction therapy for acute myeloid leukaemia (AML) are at high risk of developing invasive fungal disease (IFD). Newer therapies with targeted antileukemic agents and the emergence of azole resistance pose a challenge to the strategy of primary antifungal prophylaxis. We report the experience of a diagnostic-driven care pathway (DCP) for the management of IFD in these patients, using only culture-directed mould inactive prophylaxis. Methods: Retrospectively, we used a single-centre study of consecutive patients receiving intensive chemotherapy for myeloid malignancies between 2014 and 2021. DCP consisted of serial cultures and serum galactomannan (sGM) screening, CT imaging, and bronchoscopy to direct targeted antifungal treatment. IFD was classified according to the 2020 EORTC/MSGERC criteria. Results: A total of 192 patients with myeloid malignancies received 300 courses of intensive chemotherapy. There were 14 cases of invasive yeast infections and 18 of probable/proven invasive mould disease (IMD). The incidence of probable/proven IMD during the first cycle of remission-induction chemotherapy was 4.6% (n = 9). sGM remained negative in all cases of invasive aspergillosis (IA), with positive mycology findings in bronchoalveolar lavage. All-cause mortality was 9.4% (n = 18) 100 days after starting chemotherapy and was comparable between patients with or without IFD. The fungal-related mortality was 1% (n = 2). Conclusion: Diagnostic-driven based management without universal mould active prophylaxis is a feasible strategy in the management of IFD and limits unnecessary antimould treatment during intensive chemotherapy. The poor performance of serial serum galactomannan screening in detecting IA warrants further investigation.