TULAREMIA PRESENTING AS LARGE GI ULCERATION AND HEMORRHAGE

SESSION TITLE: Critical Care Infections SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 09:15 am - 10:15 am INTRODUCTION: Francisella tularensis is a zoonotic disease by an aerobic, gram negative coccobacillus. It is transmitted by exposure to infected animal or vectors in individuals who landscape or camp. Common symptoms are fever, chills, anorexia, and headache. Abdominal tularemia can present with abdominal pain, emesis, diarrhea, and rarely intestinal ulceration and hemorrhage. It is treated with aminoglycosides, fluoroquinolones and tetracycline. CASE PRESENTATION: 38-year-old male presented with fever, cough, anorexia, and black stool for 5 days. Patient worked as a landscaper. He has no pets, travel history or sick contacts. He does not take any medications at home. Physical exam was significant for sinus tachycardia and rhonchi of right upper lobe. Significant labs include WBC of 9.8 with 41% bands, hemoglobin 15.5, sodium 125, procalcitonin 27.3, and lactic acid 1.8. COVID-19, MRSA, Legionella and Pneumococcal urine antigen were negative. CTA chest revealed mass-like opacity in right upper lobe with multiple bilateral pulmonary nodules. Lower respiratory culture showed Candida albicans. Patient was empirically started on ceftriaxone and azithromycin. He was transferred to intensive care for worsening respiratory status and was placed on non-invasive ventilation on hospital day 1. Antibiotics were broadened to ceftaroline and levofloxacin due to suspicion of tularemia. Amphotericin B was added. Labs for Histoplasma, Blastomyces, TB, Leptospira, and HIV were negative. Patient then suffered a cardiac arrest on hospital day 2 after having large brown secretions pouring from his mouth. Cardiopulmonary resuscitation was initiated and patient was intubated and started on vasopressors with return of spontaneous circulation. Massive blood transfusion protocol was initiated. Emergent bedside upper endoscopy showed large blood clot adherent to duodenal ulcer. Interventional radiology planned on performing gastric duodenal artery embolization. However, patient suffered two more cardiac arrest with resuscitation efforts terminated per family request. Karius Digital Culture later was positive for Francisella tularensis. Autopsy revealed diffuse alveolar hemorrhage, hilar lymphadenopathy, and perforated duodenal ulceration with large adherent clot. DISCUSSION: Gastrointestinal tularemia is rare and usually from drinking contaminated water or oral inoculation of bacteria. Intestinal tract involvement can present with mesenteric lymphadenopathy and ulcerative lesions resulting in gastrointestinal bleeding with case fatality rate of 50%. Even though this is noted in the literature, to our knowledge no case reports have been published. CONCLUSIONS: Careful history taking and early identification of risk factors are important when severe tularemia infection is suspected such as in individuals with extensive outdoor activities. Treatment should be empirically initiated in high risk patients. Reference #1: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4585636/ Reference #2: https://casereports.bmj.com/content/2017/bcr-2017-22125. Reference #3: Altman GB, Wachs JE. Tularemia: A pathogen in nature and a biological weapon. Aaohn Journal. 2002 Aug;50(8):373-9. DISCLOSURES: No relevant relationships by Maria Haider Baig

POST-COVID-19 ASPERGILLOSIS

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

Screening of drug databank against WT and mutant main protease of SARS-CoV-2: Towards finding potential compound for repurposing against COVID-19

Although several pharmacological agents are under investigation to be repurposed as therapeutic against COVID-19, not much success has been achieved yet. So, the search for an effective and active option for the treatment of COVID-19 is still a big challenge. The Spike protein (S), RNA-dependent RNA polymerase (RdRp), and Main protease (Mpro) are considered to be the primary therapeutic drug target for COVID-19. In this study we have screened the drugbank compound library against the Main Protease. But our search was not limited to just Mpro. Like other viruses, SARS-CoV-2, have also acquired unique mutations. These mutations within the active site of these target proteins may be an important factor hindering effective drug candidate development. In the present study we identified important active site mutations within the SARS-CoV-2 Mpro (Y54C, N142S, T190I and A191V). Further the drugbank database was computationally screened against Mpro and the selected mutants. Finally, we came up with the common molecules effective against the wild type (WT) and all the selected Mpro. The study found Imiglitazar, was found to be the most active compound against the wild type of Mpro. While PF-03715455 (Y54C), Salvianolic acid A (N142S and T190I), and Montelukast (A191V) were found to be most active against the other selected mutants. It was also found that some other compounds such as Acteoside, 4-Amino-N- {4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide, PF-00610355, 4-Amino-N-4-[2-(2,6-Dimethyl-Phenoxy)-Acetylamino]-3-Hydroxy-1-Isobutyl-5-Phenyl-Pentyl}-Benzamide and Atorvastatin were showing high efficacy against the WT as well as other selected mutants. We believe that these molecules will provide a better and effective option for the treatment of COVID-19 clinical manifestations.