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Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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Background: Improving basic infection control (IC) practices, diagnostics and anti-microbial stewardship (AMS) are key tools to handle antimicrobial resistance (AMR). Material(s) and Method(s): This is a retrospective study done over 6 years (2016-2021) in an oncology centre in North India with many on-going interventions to improve IC practices, diagnostics and AMS. This study looked into AMR patterns from clinical isolates, rates of hospital acquired infections (HAI) and clinical outcomes. Result(s): Over all, 98,915 samples were sent for culture from 158,191 admitted patients. Most commonly isolated organism was E. coli (n = 6951;30.1%) followed by Klebsiella pneumoniae (n = 5801;25.1%) and Pseudomonas aeroginosa (n = 3041;13.1%). VRE (Vancomycin resistant Enterococcus) rates fell down from 43.5% in Jan-June 2016 to 12.2% in July-Dec 2021, same was seen in CR (carbapenem resistant) Pseudomonas (23.0%-20.6%, CR Acinetobacter (66.6%-17.02%) and CR E. coli (21.6%-19.4%) over the same study period. Rate of isolation of Candida spp. from non-sterile sites also showed reduction (1.68 per 100 patients to 0.65 per 100 patients). Incidence of health care associated infections also fell from 2.3 to 1.19 per 1000 line days for CLABSI, 2.28 to 1.88 per 1000 catheter days for CAUTI. There was no change in overall mortality rates across the study period. Conclusion(s): This study emphasizes the point that improving compliance to standard IC recommendations and improving diagnostics can help in reducing the burden of antimicrobial resistance.Copyright © 2023 Indian Association of Medical Microbiologists
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Intro: Invasive aspergillosis of CNS is a severe form of aspergillosis & is associated with high mortality. Most of these cases are suspected & diagnosed in neutropenic patients. We hereby describe a series of 15 patients with CNS aspergillosis in non-neutropenic patients from a tertiary care hospital in India. Method(s): All patients with clinical & radiological features suggestive of CNS aspergillosis were screened for microbiological evidence of invasive aspergillosis, either by demonstration of hyphae by microscopy or histology, culture or galactomannan assay. Patients demographic details, clinical features, risk factors, diagnosis, management & outcome details were documented. Finding(s): A total of 15 patients were found to have CNS aspergillosis, 5 isolated CNS infections & 10 showing concomitant CNS & pulmonary aspergillosis in one between January 2021 to July 2022. The average age was 41.46+/-14.6y, with majority being male. Among the risk factors, most common ones were fungal sinusitis (46.6%), steroid use (40%), COVID-19 (33.3%). One patient had history of endoscopic sinus repair, another had h/o lung abscess. Most common symptoms of CNS aspergillosis were headache (73.3%), fever (60%), altered sensorium (53.3%) & seizures (47.6%). Radiologically, the common findings included ring enhancing lesion, s/o cerebral abscesses were observed in four patients. Direct microscopy s/o fungal hyphae were reported in 5 patients, with 4 culture positives. Average serum galactomannan was 1, while CSF galactomannan showed better sensitivity with mean CSF galactomannan being 2.53. Almost all patients were treated with Voriconazole based on weight, but showed high mortality of 60% even after initiation of therapy. Complete resolution were seen in only two patients, while 4 patients remaining static in improvement during 6 months follow up. Conclusion(s): Invasive CNS aspergillosis must be suspected even with nonneutropenic patients with newer emerging risk factors like steroid use, COVID-19 & h/o fungal sinusitis presenting with clinical & radiological manifestations.Copyright © 2023
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Invasive pulmonary aspergillosis is associated with high mortality. For diagnosis, galactomannan-antigen in serum and bronchoalveolar lavage fluid is recommended, with higher sensitivity in bronchoalveolar lavage fluid. Because of invasiveness, bronchoalveolar lavage might be withheld due to patients' or technical limitations, leading to a delay in diagnosis while early diagnosis is crucial for patient outcome. To address this problem, we performed an analysis of patient characteristics of intubated patients with invasive pulmonary aspergillosis with comparison of galactomannan-antigen testing between non-directed bronchial lavage (NBL) and bronchoalveolar lavage fluid. A total of 32 intubated ICU patients with suspected invasive pulmonary aspergillosis could be identified. Mycological cultures were positive in 37.5% for A. fumigatus. Galactomannan-antigen in NBL (ODI 4.3 ± 2.4) and bronchoalveolar lavage fluid (ODI 3.6 ± 2.2) showed consistent results (p-value 0.697). Galactomannan-antigen testing for detection of invasive pulmonary aspergillosis using deep tracheal secretion showed comparable results to bronchoalveolar lavage fluid. Because of widespread availability in intubated patients, galactomannan-antigen from NBL can be used as a screening parameter in critical risk groups with high pretest probability for invasive aspergillosis to accelerate diagnosis and initiation of treatment. Bronchoalveolar lavage remains the gold standard for diagnosis of invasive aspergillosis to be completed to confirm diagnosis, but results from NBL remove time sensitivity.
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Objective. To study spectrum of pathogens and the time to colonization of respiratory samples in patients with severe and critical COVID-19 as well as to analyze incidence of nosocomial infections and structure of prescribed antibacterial drugs. Materials and methods. The prospective observational study included patients aged 18 years and older with confirmed severe and critical COVID-19 from December 2021 to February 2022. During the first 48 hours and then every 2-3 days of hospitalization, a respiratory sample was collected: sputum, tracheal aspirate (if intubated), bronchoalveolar lavage (if bronchoscopy was performed) for microscopy and microbiological examination. Some patients were screened for invasive aspergillosis. Clinical and demographic data, comorbidities, pathogenetic therapy for COVID-19, antibiotic therapy, cases of probable/documented bacterial nosocomial infections, antibiotic-associated diarrhea, and hospital treatment outcomes were recorded. Results. A total of 82 patients were included in this study. Patients with lung parenchyma involvement of more than 50% by computer tomography predominated;most of them (77%) required intubation and mechanical ventilation due to progression of respiratory failure, and 76% of patients had a lethal outcome. During the first 48 hours, a respiratory sample was obtained from 47 patients;the rest of the patients presented with non-productive cough. No growth of microorganisms was detected in 31 (36.8%) cases;clinically significant pathogens were detected in 16 (19.5%) patients. A subsequent analysis included data from 63 patients with a sufficient number of samples for dynamic observation were used. During the first 3 days of ICU stay, the most common bacterial pathogens were Klebsiella pneumoniae without acquired antibiotic resistance and methicillin-susceptible Staphylococcus aureus. From 3rd day and afterwards, an increase in the proportion of Acinetobacter baumannii, other non-fermenting bacteria, and carbapenem-resistant Enterobacterales was noted. Among the pathogens causing lower respiratory tract infections, A. baumannii and carbapenem-resistant K. pneumoniae were predominant pathogens and accounted for 76% of cases. Positive galactomannan test results were obtained in 4 cases. Conclusions. The study confirmed importance of bacterial nosocomial infections in patients with severe and critical COVID-19. In the case of the development of nosocomial lower respiratory tract infections, empirical antimicrobial therapy should take into account the predominance of carbapenem-resistant Enterobacteria and A. baumannii, as well as the possibility of invasive aspergillosis.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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Objective. To study risk factors, clinical and radiological features and effectiveness of the treatment of invasive aspergillosis (IA) in adult patients with COVID-19 (COVID-IA) in intensive care units (ICU). Materials and methods. A total of 60 patients with COVID-IA treated in ICU (median age 62 years, male - 58%) were included in this multicenter prospective study. The comparison group included 34 patients with COVID-IA outside the ICU (median age 62 years, male - 68%). ECMM/ISHAM 2020 criteria were used for diagnosis of CAPA, and EORTC/MSGERC 2020 criteria were used for evaluation of the treatment efficacy. A case-control study (one patient of the main group per two patients of the control group) was conducted to study risk factors for the development and features of CAPA. The control group included 120 adult COVID-19 patients without IA in the ICU, similar in demographic characteristics and background conditions. The median age of patients in the control group was 63 years, male - 67%. Results. 64% of patients with COVID-IA stayed in the ICU. Risk factors for the COVID-IA development in the ICU: chronic obstructive pulmonary disease (OR = 3.538 [1.104-11.337], p = 0.02), and prolonged (> 10 days) lymphopenia (OR = 8.770 [4.177-18.415], p = 0.00001). The main location of COVID-IA in the ICU was lungs (98%). Typical clinical signs were fever (97%), cough (92%), severe respiratory failure (72%), ARDS (64%) and haemoptysis (23%). Typical CT features were areas of consolidation (97%), hydrothorax (63%), and foci of destruction (53%). The effective methods of laboratory diagnosis of COVID-IA were test for galactomannan in BAL (62%), culture (33%) and microscopy (22%) of BAL. The main causative agents of COVID-IA are A. fumigatus (61%), A. niger (26%) and A. flavus (4%). The overall 12-week survival rate of patients with COVID-IA in the ICU was 42%, negative predictive factors were severe respiratory failure (27.5% vs 81%, p = 0.003), ARDS (14% vs 69%, p = 0.001), mechanical ventilation (25% vs 60%, p = 0.01), and foci of destruction in the lung tissue on CT scan (23% vs 59%, p = 0.01). Conclusions. IA affects predominantly ICU patients with COVID-19 who have concomitant medical conditions, such as diabetes mellitus, hematological malignancies, cancer, and COPD. Risk factors for COVID-IA in ICU patients are prolonged lymphopenia and COPD. The majority of patients with COVID-IA have their lungs affected, but clinical signs of IA are non-specific (fever, cough, progressive respiratory failure). The overall 12-week survival in ICU patients with COVID-IA is low. Prognostic factors of poor outcome in adult ICU patients are severe respiratory failure, ARDS, mechanical ventilation as well as CT signs of lung tissue destruction.Copyright © 2022, Interregional Association for Clinical Microbiology and Antimicrobial Chemotherapy. All rights reserved.
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Introduction: The most widely used marker for the diagnosis of invasive aspergillosis (IA) is the detection of galactomannan by ELISA. This study describes the evaluation of the results obtained by Euroimmun Aspergillus antigen ELISA (EIA-GM-E) in serum samples and bronchoalveolar lavage fluid (BAL) from patients at risk of IA, and compares these results with those obtained by Bio-Rad Galactomannan EIA (EIA-GM-BR). Method(s): Anonymous retrospective case-control comparative study in 64 serum samples and 28 BAL from 51 patients. Result(s): Overall agreement of the results of the two assays was observed in 72 of 92 samples (78.3%). The sensitivity of EIA-GM-BR and EIA-GM-E in serum samples was 88.9% and 43.2%, respectively, and 100% and 88.9% for BAL. The specificity of EIA-GM-BR and EIA-GM-E in serum samples was 91.9% for both assays, and 68.4% and 84.2% in BAL. There were no statistically significant differences in the results of both assays. Conclusion(s): Both methods show good results for the discrimination of patients with IA when BAL is tested, or serum in case of EIA-GM-BR.Copyright © 2021 Sociedad Espanola de Enfermedades Infecciosas y Microbiologia Clinica
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PURPOSE: Invasive cerebral aspergillosis (ICA) is a rare but fatal infection affecting neutropenic immunocompromised patients. Recently cases have been reported in non-neutropenic settings also. We hereby present a series of ICA cases in non-neutropenic patients diagnosed at our tertiary care centre in Western India between March to October 2021. METHODS: All patients with clinico-radiological suspicion of CNS infections were analysed. Data regarding Clinico-radiological features, diagnosis, treatment and outcome were collected. After ruling out bacterial, viral and mycobacterial causes, appropriate samples were sent for KOH (potassium hydroxide) wet mount, fungal culture, histopathology and serum/CSF galactomannan. RESULTS: A total of four patients were diagnosed with ICA with a mean age of 43.5 years. Three patients had significant comorbidities; Diabetes mellitus, chronic liver disease and COVID-19 pneumonia treated with dexamethasone, respectively. One patient had no known predisposing factor. Radiologically, one patient presented with a frontal brain abscess and two patients had multiple subcortical hyperintensities. Three patients were diagnosed based on CSF galactomannan (Platelia™ Aspergillus antigen, Bio-Rad, France) with OD >1 and one patient had high serum galactomannan (OD >2). CSF culture grew Aspergillus species in two patients. All patients were treated with Voriconazole. One patient recovered, and the remaining three succumbed due to delayed presentation and extensive cerebral involvement. CONCLUSION: Even in non-neutropenic patients, a high index of suspicion is warranted for cerebral aspergillosis. CSF galactomannan can be considered a reliable marker for diagnosing ICA in non-neutropenic settings. Early diagnosis allows timely antifungal therapy, which could be a key to improving the outcomes.
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Aspergillosis , COVID-19 , Humans , Adult , Aspergillosis/diagnosis , Aspergillosis/drug therapy , Aspergillus , Voriconazole/therapeutic use , France , Mannans , GalactoseABSTRACT
Objective: The objective of this study is to report the frequency and clinical characteristic of IFI in COVID-19 patients. Method(s): This observational study was conducted in Karachi, Pakistan from March 2020-April 2021. Patients with COVID-19 associated aspergillosis (CAPA) were diagnosed using ECMM/ISHAM criteria modified to include tracheal aspirate culture and/or Galactomannan Index (GMI) >4.5 in the possible CAPA category. COVID-19 associated candidemia (CAC) was defined by isolation of Candida species from blood cultures. COVID-19 associated mucormycosis (CAM) was defined as updated EORTC/MSG criteria with inclusion of COVID-19 as host factor. Pneumocystis jirovecii pneumonia (PJP) was defined by consistent clinical and radiological features and PCR positivity. Result(s): During the study period a total of 123 (3.3%) IFI in 3506 hospitalized COVID-19 patients were identified. This included 78 (2.2%) CAPA patients (42 probable;36 possible), 29 (0.8%) CAC (5 C. auris;24 non-C. auris), 10 (0.3%) CAM (7 pulmonary;3 rhinocerebral), 3 (0.08%) PJP and three (0.08%) cases of rare invasive fungal infections (2 C. neoformans;1 Trichosporon asahii). Outcome data was available on 117/123 patients. Of these 117 patients, 78 expired (66.7%). These include 52/74 (70%) CAPA patients, 17/27 (63%) CAC patients, 7/10 (70%) CAM patients and 2/3 (67%) PJP patients. Conclusion(s): We report a rate of 3.3% IFI amongst hospitalized COVID-19 patients at our center. We consider this rate to be an underestimate due to less bronchoscopic procedures and inclusion of only candidemia cases. We also report higher mortality rate with IFI in our patients than global data probably due to delayed diagnosis, co-infections and limited therapeutic options.
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Background: With the development of coronavirus disease-2019 (COVID-19) pandemic, there is also increased risk of multiple secondary infections either disease- or drug-related. It includes many bacterial as well as invasive fungal infections. Patients and methods: There was suspicion of invasive pulmonary aspergillosis (IPA) infection in COVID-19 patients who were critically ill and had acute respiratory distress syndrome (ARDS). We did radiological evaluation and galactomannan assay in these patients. Result: We have diagnosed COVID-19-associated pulmonary aspergillosis (CAPA) in these patients and started antifungal treatment with voriconazole in all of these COVID-19 patients. Conclusion: It is very important to report such cases, so that healthcare professionals and authorities related to healthcare will be aware of and may also prepare for the increasing burden of this complication. We describe a case series of CAPA infection. How to cite this article: Sharma K, Kujur R, Sharma S, Kumar N, Ray MK. COVID-19-associated Pulmonary Aspergillosis: A Case Series. Indian J Crit Care Med 2022;26(9):1039-1041.
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(1) Background: Coronavirus disease 2019 (COVID-19)-associated pulmonary aspergillosis (CAPA) raises concerns to contribute to an increased mortality. The incidence of CAPA varies widely within hospitals and countries, partly because of difficulties in obtaining a reliable diagnosis. (2) Methods: Here, we assessed Aspergillus culture-positive and culture-negative respiratory tract specimens via direct fungal microscopy (gold standard) and compared the results with galactomannan enzyme immunoassay (GM-EIA) and Aspergillus PCR. (3) Results: 241 respiratory samples from patients suffering from SARS-CoV-2 pneumonia were evaluated. Results showed both diagnostic tools, Aspergillus PCR and GM-EIA, to be positive or negative displaying a sensitivity of 0.90, a specificity of 0.77, a negative predictive value (NPV) of 0.95, and a positive predictive value (PPV) of 0.58 in Aspergillus sp. culture and microscopic-positive specimens. Non-bronchoalveolar lavage (BAL) samples, obtained within a few days from the same patient, showed a high frequency of intermittent positive or negative GM-EIA or Aspergillus PCR results. Positivity of a single biomarker is insufficient for a proper diagnosis. A broad spectrum of Aspergillus species was detected. (4) Conclusions: Our study highlights the challenges of combined biomarker testing as part of diagnosing CAPA. From the results presented, we highly recommend the additional performance of direct microscopy in respiratory specimens to avoid overestimation of fungal infections by applying biomarkers.
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BACKGROUND: Since February 2021 active screening of COVID-19-associated pulmonary aspergillosis (CAPA) has been implemented in our institution. OBJECTIVES: To evaluate CAPA incidence in our centre and evaluate performance of our screening protocol. METHODS: 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 >7 pg/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. RESULTS: 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). CONCLUSIONS: 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.
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Nanocomposite gels are novel materials mainly used in the medical field for the control drug release and distribution. In this study, the effect of the concentration of galactomannan/zinc oxide nanocomposite in a polymeric Carbopol matrix to obtain a functional nanocomposite gel was studied. The swelling, thermogravimetric, rheological, and antibacterial properties against Escherichia coli and Staphylococcus aureus were evaluated. The results indicate that there is a direct effect between the amount of the employed nanocomposite and the properties studied in the gels. In this regard, we present a formulation that demonstrates that the prepared nanocomposite gel has ideal properties to be used in the medical field as an antibacterial agent.
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SESSION TITLE: Drug-Induced and Associated Critical Care Cases Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Lung toxicity due to antineoplastic therapy is reported with both cytotoxic and molecularly targeted agents [1]. We present one such case of lung injury induced by capecitabine. CASE PRESENTATION: A 79-year-old female with history of triple negative infiltrating duct carcinoma of the right breast (status post mastectomy and adjuvant chemotherapy with docetaxel and cyclophosphamide 3 years prior) presented to the hospital with dyspnea on exertion following her fourth cycle of capecitabine therapy for breast cancer recurrence. Patient developed nausea, vomiting, and malaise with cycles 1, 2, and 3 of capecitabine therapy with onset of severe dyspnea on exertion, cough, and hypoxia following cycle 4. Computed tomography (CT) scan of the chest on admission showed consolidative opacities in the right upper, right middle, and anterior right lower lobe along with smaller opacities in the left lung apex and small subcentimeter nodules;no pulmonary embolism. Antibiotics were given for a short duration for suspected pneumonia without improvement. Capecitabine was held on discharge. She presented again to the emergency room with worsening shortness of breath, diarrhea, fatigue, and dizziness. COVID test was negative. Chest x-ray redemonstrated patchy airspace disease involving the right apical, lateral, mid lower lung field. Oral steroids were recommended for suspected organizing pneumonia, but the patient refused due to concerns about side effects. Her hospital course was complicated by Clostridium difficile infection (treated with oral vancomycin) and left lower extremity deep venous thrombosis (treated with anticoagulation). Subsequently she followed up with pulmonology outpatient. Repeat imaging showed evolving infiltrates in the same areas with elevated aspergillus IgG level (18.0 mcg/ml) and IgE (178 kU/L) but negative galactomannan and sputum bacterial/fungal/acid fast cultures. Oral steroids were initiated with clinical and symptomatic improvement. DISCUSSION: Capecitabine is a prodrug of fluorouracil (antimetabolite). It is used as a chemotherapy agent in multiple types of cancer including breast cancer. Respiratory side effects include cough (<7%) and bronchitis (<5%). Lung injury/pneumonitis is a rare complication with only a few cases reported to date [2,3]. The timing of symptoms with chemotherapy administration and the negative infectious work-up supports capecitabine as the inciting etiology of lung injury. Withholding chemotherapy and starting systemic steroids were effective treatments in this case of chemotherapy induced lung toxicity. CONCLUSIONS: Capecitabine induced lung injury is a rare but important entity and should always be kept in mind while evaluating dyspnea in cancer patients. Reference #1: Capri G, Chang J, et al. An open-label expanded access study of lapatinib and capecitabine in patients with HER2-overexpressing locally advanced or metastatic breast cancer. Ann Oncol. 2010;21(3):474. Epub 2009 Oct 8. DOI: 10.1093/annonc/mdp373 Reference #2: C. J. Benthin, G. Allada. Capecitabine-Induced Lung Injury. American Journal of Respiratory and Critical Care Medicine 2016;193:A1653. Reference #3: Andrew K Chan, Bok A Choo, John Glaholm. Pulmonary toxicity with oxaliplatin and capecitabine/5-Fluorouracil chemotherapy: a case report and review of the literature. Onkologie. 2011;34(8-9):443-6. doi: 10.1159/000331133. Epub 2011 Aug 19. DISCLOSURES: No relevant relationships by William Karkowsky No relevant relationships by Chahat Puri No relevant relationships by Sahib Singh
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SESSION TITLE: Pathologies of the Post-COVID-19 World SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: COVID-19 Associated Pulmonary Aspergillosis (CAPA) is a subset of invasive pulmonary aspergillosis occurring in patients actively infected with or recovering from COVID-19. It has mostly been described in immunocompromised or severely ill patients requiring invasive mechanical ventilation[1-6]. The authors report a case of CAPA infection in an ambulatory and immunocompetent patient with prior lung resection. CASE PRESENTATION: A 20-year-old male presented to a Comprehensive Cancer Center for fever and hemoptysis. He carried a diagnosis of metastatic germ cell tumor to his lungs, status post left upper-lobe wedge resection. He had completed bleomycin, etoposide, and cisplatin (BEP) chemotherapy one year earlier. He was recently diagnosed with COVID-19 one month prior to admission and treated as an outpatient with monoclonal antibodies. He reported ongoing cough productive of clear sputum since his diagnosis, which had worsened over the previous two days and was now blood-tinged. He had been afebrile for weeks before noting new fevers over the same period. Physical examination was notable for fever to 38.6°C and lungs clear to auscultation. His labs were significant for a WBC of 14.5 K/mcl (82.5% neutrophils), Cr 2.1 mg/dL (baseline 1.5 mg/dL), and normal platelets and coagulation studies. Serum Aspergillus galactomannan was normal. Repeat SARS-CoV-2 PCR was negative. Chest x-ray was unchanged. V/Q scan showed no evidence of pulmonary embolism. Non-contrast CT chest performed on hospital day #4 revealed a partial opacification and increased wall thickness of patient's largest left upper lobe surgical cavitation (see Image 1). A bronchoscopy was performed day #6, with bronchoalveolar lavage (BAL) galactomannan >5.56 (normal <0.5)7;fungal culture was significant for septate hyphae. He was started on voriconazole with improvement in his symptoms and discharged day #9. DISCUSSION: Immunocompromised patients with prolonged neutropenia, solid-organ or stem cell transplants, and patients with advanced AIDS are at highest risk of contracting PA[8-9]. ARDS secondary to viral pneumonia is also a common precipitant in immunocompetent patients[1-6,10,11]. The exact mechanism of this association remains unknown, but it is postulated to occur due to multiple factors, including host immune dysregulation[1,2], widespread exposure to corticosteroids[1,2], concomitant lung disease[1], and viral-induced lymphopenia[2]. We report a case of an immunocompetent patient with prior lung resection recovering from COVID-19 who experienced a secondary worsening of symptoms ultimately found to have CAPA to further highlight the link between these conditions. CONCLUSIONS: While many of CAPA case reports describe patients with typical risk profiles for CAPA, this case suggests that clinicians should consider structural lung disease alone in an otherwise immunocompetent, ambulatory individual to be a potential risk factor. Reference #1: See Image 2 for full list of references. DISCLOSURES: No relevant relationships by Raphael Rabinowitz No relevant relationships by Matthew Velez
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SESSION TITLE: Unusual Pneumonias SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/19/2022 12:45 pm - 1:45 pm INTRODUCTION: Invasive pulmonary aspergillosis (IPA) commonly occurs in the setting of immunosuppression. Underlying lung disease is a well-known risk factor for IPA;however, interstitial lung disease (ILD) has not been recognized as a risk factor for IPA[1]. CASE PRESENTATION: A 40-year-old male with a history of a failed kidney transplant now on hemodialysis (HD), Juvenile Rheumatoid Arthritis, Mixed Connective Tissue Disease, Aspergilloma led to right lower lobectomy a year ago, COVID-19 infection three months ago, chronic lung disease (CLD) thought to be due to Nonspecific interstitial pneumonia (NSIP) presented with dyspnea. He had several hospitalizations for respiratory failure needing intubation or NIPPV, broad-spectrum antibiotics, steroids, and HD with improved respiratory status, eventually discharged. Bronchoalveolar lavage fluid culture grew aspergillus terreus but was negative for Pneumocystis (PCP), bacteria, acid-fast bacilli, and Nocardia. The transbronchial biopsies showed mixed inflammatory type and fungal forms in one specimen. Additionally, the initially negative galactomannan converted into a serial rise in galactomannan (>3.75 Index) along with a rise in beta d-glucan (>500 pg/ml). Unfortunately, he had gaps in antifungals and was readmitted similarly. Micafungin was added for dual fungal coverage and was planned for surgical lung biopsy to characterize ILD further once his respiratory status allows. DISCUSSION: He has multiple risk factors for developing IPA, such as high-dose steroids for ILD and recent COVID infection. Initially, respiratory failure was thought to be due to exacerbation of ILD, and suspicion for IPA was low because of lack of neutropenia, negative fungal biomarkers, lack of classic findings on lung imaging, and in-hospital clinical improvement with steroids. However, the eventual course of recurrent respiratory failure while on high-dose steroids, along with gaps in antifungal therapy and continued growth of Aspergillus, made IPA the most likely diagnosis. For IPA, the mainstay of treatment is both adequate antifungal therapy and reduction in immunosuppression to the extent possible[2];however, it is unclear if his underlying ILD can tolerate steroid taper. He will need a lung transplant after adequately treating IPA. CONCLUSIONS: There are no current guidelines on simultaneously treating IPA and NSIP. It is challenging to balance reduction in immunosuppression as tolerated for ILD and concurrently maintain antifungal therapy. During this patient's hospitalization, there have been considerations of using a steroid-sparing agent for his suspected NSIP, however, in the setting of active infection, its benefit is debatable.[3] Reference #1: Matsuyama H, Miyoshi S, Sugino K, et al. Fatal Invasive Pulmonary Aspergillosis Associated with Nonspecific Interstitial Pneumonia: An Autopsy Case Report. Intern Med. 2018;57(24):3619-3624. doi:10.2169/internalmedicine.1144-18 Reference #2: Thomas F. Patterson, George R. Thompson, III, David W. Denning, Jay A. Fishman, Susan Hadley, Raoul Herbrecht, Dimitrios P. Kontoyiannis, Kieren A. Marr, Vicki A. Morrison, M. Hong Nguyen, Brahm H. Segal, William J. Steinbach, David A. Stevens, Thomas J. Walsh, John R. Wingard, Jo-Anne H. Young, John E. Bennett, Practice Guidelines for the Diagnosis and Management of Aspergillosis: 2016 Update by the Infectious Diseases Society of America, Clinical Infectious Diseases, Volume 63, Issue 4, 15 August 2016, Pages e1–e60, https://doi.org/10.1093/cid/ciw326 Reference #3: Mezger, M., Wozniok, I., Blockhaus, C., Kurzai, O., Hebart, H., Einsele, H., & Loeffler, J. (2008). Impact of mycophenolic acid on the functionality of human polymorphonuclear neutrophils and dendritic cells during interaction with Aspergillus fumigatus. Antimicrobial agents and chemotherapy, 52(7), 2644–2646. https://doi.org/10.1128/AAC.01618-07 DISCLOSURES: No relevant relationships by Nasir Alhamdan No relevant relati nships by Parth Jamindar No relevant relationships by Harshitha Mergey Devender No relevant relationships by Abira Usman No relevant relationships by Vishruth Vyata
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SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Since the start of Covid-19 pandemic, several respiratory microorganisms have been identified that cause coinfection with Sars-Cov-2. Bacteria like Staphylococcus aureus and viruses like influenza are some of the identified pathogens. Rarely, fungal infections from Aspergillus are also being reported. CASE PRESENTATION: 59-year-old male with past medical history of hypertension and hyperlipidemia was admitted for shortness of breath and was found to be positive for Covid-19. He received Remdesivir, dexamethasone & tocilizumab. He required non-invasive ventilation via continuous positive airway pressure but continued to remain hypoxemic with elevated procalcitonin, he was treated with cefepime for bacterial pneumonia. Patient required emergent intubation and eventually underwent tracheostomy. He developed methicillin-resistant Staphylococcus aureus pneumonia for which he received vancomycin. He was eventually discharged to long term acute care facility. Patient was readmitted after 2 months due to worsening respiratory status. Computed Tomography Angiography of chest was negative for pulmonary embolism but showed pleural effusion. He underwent thoracentesis which showed exudative effusion with negative cultures. Echocardiogram showed right heart failure. Patient's symptoms were believed to be due to Covid-19 fibrosis. He required home oxygen and also received pulmonary rehabilitation. One year after the initial Covid-19 infection, he developed pulmonary hypertension and was referred for lung transplant consultation. However, he developed severe hemoptysis requiring intubation and vasopressors. Galactomannan was positive, Karius digital culture revealed Aspergillus Niger for which he received voriconazole. He was not deemed a suitable candidate for lobectomy. Patient developed arrhythmia and had prolonged QT interval so voriconazole was switched to Isavuconazole. He continued to have hemoptysis and his condition did not improve so family requested to transition care and patient passed away. DISCUSSION: Several studies have proven co-infection of Aspergillus with Covid-19. This case highlights Aspergillus infection approximately 1 year after initial Covid-19 infection. Sars-Cov-2 causes damage to airway lining which can result in Aspergillus invading tissues. IL-6 is increased in severe Covid-19 infection. Tocilizumab is an anti-IL-6 receptor antibody that has been approved for treatment of Covid-19 pneumonia. However, IL-6 provides immunity against Aspergillus so use of tocilizumab decreases protection against Aspergillosis which is usually the reason for co-infection. However, in this case patient developed fungal infection later during Covid-19 fibrosis stage. CONCLUSIONS: Recognizing fungal etiology early on is important in Covid-19 patients as mortality is high and appropriate intervention can reduce morbidity and mortality. Some patient may eventually require lung resection. Reference #1: Kakamad FH, Mahmood SO, Rahim HM, Abdulla BA, Abdullah HO, Othman S, Mohammed SH, Kakamad SH, Mustafa SM, Salih AM. Post covid-19 invasive pulmonary Aspergillosis: a case report. International journal of surgery case reports. 2021 May 1;82:105865. Reference #2: Nasrullah A, Javed A, Malik K. Coronavirus Disease-Associated Pulmonary Aspergillosis: A Devastating Complication of COVID-19. Cureus. 2021 Jan 30;13(1). Reference #3: Dimopoulos G, Almyroudi MP, Myrianthefs P, Rello J. COVID-19-associated pulmonary aspergillosis (CAPA). Journal of Intensive Medicine. 2021 Oct 25;1(02):71-80. DISCLOSURES: No relevant relationships by Maria Haider Baig
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SESSION TITLE: Infectious Complications with Obstructions and Connections SESSION TYPE: Case Reports PRESENTED ON: 10/17/2022 03:15 pm - 04:15 pm INTRODUCTION: Invasive pulmonary fungal infections are a challenge for diagnosis. One of the most common types is Invasive pulmonary aspergillosis. It occurs usually among immunocompromised patients [1], so an early diagnosis is warranted for potential better outcome. Evidence of calcium oxalate can be an early diagnostic tool for such an infection. The presence of calcium oxalate crystals can be detected within 24 hours under polarized light in the microbiology labs. We present this case to highlight the potential importance of pulmonary oxalosis in diagnosing pulmonary aspergillosis. CASE PRESENTATION: A 62-year-old-woman with limited breast cancer was admitted to the hospital seven days after her last cycle of docetaxel and cyclophosphamide with COVID-19 pneumonia and hypoxemic respiratory failure. She was not neutropenic. She received a full course of dexamethasone and remdesivir. Sputum cultures subsequently grew Klebsiella aerogenes for which she was treated with antibiotics but failed to significantly improve over four weeks. Repeat chest computed tomography (CT) showed progressive multifocal airspace opacities with new areas of cavitation. Patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and transbronchial biopsy. Transbronchial biopsy specimen from the right upper lobe showed bronchial mucosa and lung parenchyma with calcium oxalate crystals and no organisms. Biopsy specimen from the right middle lobe showed fungal organisms consistent with Aspergillus invading bronchial mucosa and lung parenchyma. Several days later, serum beta-D-glucan returned within normal limits, serum galactomannan was significantly elevated, and BAL culture grew Aspergillus niger. Patient improved with antifungal therapy. DISCUSSION: Fungal pneumonia has high morbidity and mortality. It is essential to start antifungal therapy as soon as possible. Pulmonary oxalosis or calcium oxalate has been seen among Aspergillus Fumigatus and Aspergillus Niger [2-3]. It is a combination of oxalic acid which is produced by Aspergillus spp. and calcium from blood supply of an invaded tissue. Further progression of lesions can be due to calcium oxalate toxicity itself [4-5]. In our case, clinical suspicion for pulmonary aspergillosis was high and we were able to document fungal invasion of lung parenchyma on one of the lung specimens. Though fungal culture is very sensitive and specific, it can take several days to result. Tissue staining for crystals can be performed quickly and provide more timely information when deciding about starting anti-fungal therapy. CONCLUSIONS: Pulmonary oxalosis, calcium oxalate deposition, can be seen in aspergillus infection and should be considered as an early diagnostic tool for invasive pulmonary aspergillosis. Reference #1: Kousha M, Tadi R, Soubani AO. Pulmonary aspergillosis: a clinical review. Eur Respir Rev. 2011;20(121): 156–174, doi: 10.1183/09059180.00001011 Reference #2: U. Pabuccuoglu, Aspects of oxalosis associated with aspergillosis in pathology specimens, Pathol. Res. Pract. 201 (2005) 363–368 Reference #3: Osholowu OS, Kak V, Singh H. Pulmonary oxalosis in pulmonary aspergillosis syndrome. Adv Respir Med. 2020;88(2):153-156. doi: 10.5603/ARM.2020.0090. PMID: 32383468. DISCLOSURES: No relevant relationships by Mohammed Alsaggaf No relevant relationships by Daniel Baram No relevant relationships by Ivana Milojevic
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Aim and objective: To elaborate the challenges faced by an ECMO patient and the issues to be overcome and how to address them and combat with the help of a multidisciplinary team. This is a case of a 34-year-old male patient without any comorbidities who tested positive for COVID on 08/07/21 who was on home quarantine for 8 days and reported to hospital on 16/07 in view of breathlessness, was started on oxygen, bipap and tried on remdesivir, steroids, and tocilizumab and baricitinib. The patient was not maintaining saturations and was intubated on 26/07 and as there was refractory hypoxaemia was initiated on ECMO on the next day. The patient was started on ceftazidime and levoflox along with voriconazole as serum galactomannan was positive and ET cultures showed Stenotrophomonas maltophilia. The patient was tracheostomized on 01/08 and was keeping well till 12/08 when there were episodes of desaturation and tachypnoea and blood culture showed Candida auris and BAL culture showed Chryseobacterium and MDR Klebsiella with NDM, OXA-48 AND VIM+. The patient developed septic shock and required dual vasopressors. BAL galactomannan had titres of 4.5 and the patient was initiated on a mixture of ceftazidime, avibactum, voriconazole, and anidulafungin. The patient started having hemoglobinuria subsequently and acute kidney injury secondary to this and required 3 sessions of dialysis and the whole ECMO circuit was changed. Improvement in the parameters followed with normalization of blood pressure and urine output too. When there was a sigh of relief as things were getting normal patient started having heavy bouts of tracheal bleeding and bronchoscopy was done again with endobronchial biopsy showing CMV endobronchitis with focal ulceration and was started on ganciclovir. There were maleana episodes too which normalized after initiation of antivirals and CMV enterocolitis was suspected to be the cause. Now the patient is on trial off mode with decannulation being planned.
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Introduction: Blastomyces species are thermally dimorphic fungi endemic to North America, especially areas bordering the Mississippi, Ohio and St. Lawrence rivers, and the Great Lakes. Blastomycosis infections are estimated to occur in 3-13% in the pediatric population. Pediatric literature for blastomycosis has been mostly limited to small studies and case series. Recent literature suggests increasing rates of infections, less morbidity and mortality as compared to adults, with asthma as the most common comorbid condition. Although pulmonary disease is the most common presentation, it rarely progresses to acute respiratory distress syndrome (ARDS). Case Description: A 17- year-old female, living in the Chicago area, and with type 1 diabetes mellitus and childhood asthma, presented to the emergency room with acute hypoxemic respiratory failure after 14 days of cough, dyspnea, chest pain, and fevers as high as 105°F. Her initial radiographic imaging revealed bilateral infiltrates and consolidations in the right middle and lower lobes. She was admitted to the step down unit for further care. A respiratory viral panel, including COVID-19 evaluation, was negative. She was started on low-flow nasal cannula, ceftriaxone, azithromycin, albuterol, and maintenance IV fluids. On hospital day 2, she was transferred to the pediatric intensive care unit for worsening respiratory distress and escalated to high-flow nasal cannula. She was treated empirically for presumed bacterial pneumonia with ceftriaxone (7-day course), azithromycin (5-day course), cefepime (5-day course), clindamycin (2-day course), and vancomycin (14-day course). Despite this treatment, repeat chest imaging showed worsening disease and she required escalation to BiPAP for progression of her ARDS and impending respiratory failure. Karius testing results indicated Blastomyces dermatitidis at low levels typically not clinically relevant. Sputum and bronchoalveolar lavage cultures demonstrated no significant pathogenic bacteria. Pathology exam of the biopsy obtained from bronchoscopy was consistent with Blastomyces. Urine antigen test was positive for both Blastomyces and Histoplasma. She clinically improved after initiating Amphotericin B lipid complex (6-day course), with transition to oral itraconazole and adjunctive therapy with IV methylprednisolone. She was discharged home after a 30-day hospital stay. Discussion: Pulmonary blastomycosis presents with a broad variety of signs and symptoms. Timely diagnosis is challenging. Pulmonary blastomycosis has no pathognomonic radiographic patterns. Severe acute pulmonary infection that fails to respond to antibacterial treatment should prompt investigation for fungal infection, including urine antigen tests for Histoplasma and Blastomyces, serum galactomannan, beta-1,3-D-glucan, and next-generation sequencing of microbial cell-free DNA (eg, Karius test). Close respiratory monitoring should occur in a pediatric intensive care unit. Conclusion: Blastomycosis is not typically in the initial differential diagnosis unless the patient has other clinical findings, fails to improve on antibacterial therapy, or has identified risk factors for exposure. Failure of prompt recognition is associated with poor outcomes, increased morbidity and mortality, increased length of hospital stay, and cost.