Granulomatous Hepatitis as Primary Manifestation of Disseminated Histoplasmosis in an Immunocompetent Host Diagnosed on EUS FNA and Liver Biopsy

Introduction: Disseminated histoplasmosis (DH) presents as primarily lung manifestations with extrapulmonary involvement in immunocompromised hosts. Granulomatous hepatitis as first presentation of DH in an immunocompetent host is uncommon. Case Description/Methods: 25-year-old female presented with one month of fever, fatigue, myalgias, 30-pound weight loss, cough, nausea, vomiting, and epigastric pain. She has lived in the Midwest and southwestern US. Presenting labs: TB 1.9 mg/dL, AP 161 U/L, AST 172 U/L, ALT 463 U/L. Workup was negative for COVID, viral/autoimmune hepatitis, sarcoidosis, tuberculosis, and HIV. CT scan showed suspected gallstones and 9 mm left lower lobe noncalcified nodule. EUS showed a normal common bile duct, gallbladder sludge and enlarged porta hepatis lymph nodes which underwent fine needle aspiration (FNA). She was diagnosed with biliary colic and underwent cholecystectomy, with white plaques noted on the liver surface (A). Liver biopsy/FNA showed necrotizing granulomas (B) and fungal yeast on GMS stain (C). Although histoplasmosis urine and blood antigens were negative, histoplasmosis complement fixation was >1:256. She could not tolerate itraconazole for DH, requiring amphotericin B. She then transitioned to voriconazole, discontinued after 5 weeks due to increasing AP. However, her symptoms resolved with normal transaminases. At one year follow up, she is asymptomatic with normal liver function tests. Discussion(s): DH is a systemic granulomatous disease caused by Histoplasma capsulatum endemic to Ohio, Mississippi River Valley, and southeastern US. DH more commonly affects immunocompromised hosts with AIDS, immunosuppressants, and organ transplant. Gastrointestinal involvement is common in DH (70-90%) with liver involvement in 90%. However, granulomatous hepatitis as primary manifestation of DH is rare (4% of liver biopsies). Hepatic granulomas are seen in < 20%. Patients may present with nonspecific systemic symptoms. Serum/urine antigens may be negative. Gold standard for diagnosis is identifying yeast on tissue stains. Recommended treatment is amphotericin B followed by 1 year of itraconazole. However, shorter treatment duration may be effective in immunocompetent hosts. This case is unique in that granulomatous hepatitis was the first presentation of DH in our immunocompetent patient diagnosed on EUS FNA and liver biopsy. Clinicians must have a high degree of suspicion for DH in patients with fever of unknown origin especially in endemic areas regardless of immunologic status. (Table Presented).

Pulmonary sarcoidosis

The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.Copyright © ERS 2022.

Transcriptome in Human Mycoses

Mycoses are infectious diseases caused by fungi, which incidence has increased in recent decades due to the increasing number of immunocompromised patients and improved diagnostic tests. As eukaryotes, fungi share many similarities with human cells, making it difficult to design drugs without side effects. Commercially available drugs act on a limited number of targets and have been reported fungal resistance to commonly used antifungal drugs. Therefore, elucidating the pathogenesis of fungal infections, the fungal strategies to overcome the hostile environment of the host, and the action of antifungal drugs is essential for developing new therapeutic approaches and diagnostic tests. Large-scale transcriptional analyses using microarrays and RNA sequencing (RNA-seq), combined with improvements in molecular biology techniques, have improved the study of fungal pathogenicity. Such techniques have provided insights into the infective process by identifying molecular strategies used by the host and pathogen during the course of human mycoses. This chapter will explore the latest discoveries regarding the transcriptome of major human fungal pathogens. Further we will highlight genes essential for host–pathogen interactions, immune response, invasion, infection, antifungal drug response, and resistance. Finally, we will discuss their importance to the discovery of new molecular targets for antifungal drugs. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Switzerland AG 2014, 2022.

Stopping Feline Coronavirus Shedding Prevented Feline Infectious Peritonitis.

After an incubation period of weeks to months, up to 14% of cats infected with feline coronavirus (FCoV) develop feline infectious peritonitis (FIP): a potentially lethal pyogranulomatous perivasculitis. The aim of this study was to find out if stopping FCoV faecal shedding with antivirals prevents FIP. Guardians of cats from which FCoV had been eliminated at least 6 months earlier were contacted to find out the outcome of their cats; 27 households were identified containing 147 cats. Thirteen cats were treated for FIP, 109 cats shed FCoV and 25 did not; a 4-7-day course of oral GS-441524 antiviral stopped faecal FCoV shedding. Follow-up was from 6 months to 3.5 years; 11 of 147 cats died, but none developed FIP. A previous field study of 820 FCoV-exposed cats was used as a retrospective control group; 37 of 820 cats developed FIP. The difference was statistically highly significant (p = 0.0062). Cats from eight households recovered from chronic FCoV enteropathy. Conclusions: the early treatment of FCoV-infected cats with oral antivirals prevented FIP. Nevertheless, should FCoV be re-introduced into a household, then FIP can result. Further work is required to establish the role of FCoV in the aetiology of feline inflammatory bowel disease.

Azole resistance screening in Aspergillus species isolated from patients with COVID-associated pulmonary aspergillosis from Pakistan

Background: COVID-19 associated pulmonary aspergillosis (CAPA) complicates the course of critically ill COVID-19 patients. Delay in diagnosis and reports of azole resistance in CAPA patients lead to adverse outcome. We had previously reported CAPA rates of 21.7% from our center with high mortality. To detect azole resistance in Aspergillus species isolated from CAPA patients, we performed azole resistance screening. Material(s) and Method(s): Aspergillus species isolated from tracheal aspirates of CAPA patients admitted in Aga Khan University Hospital, Karachi, Pakistan during July 2020- January 2022, were screened for azole resistance as per CDC protocol. Minimum inhibitory concentration of screening positive strains were determined using YeastOne Sensititre plate. Result(s): 92 Aspergillus isolates were screened from 73 CAPA patients for azole resistance. Only 2 (2.17%) A. flavus isolates showed growth on voriconazole well, while other 90 (97%) isolates were screened negative for resistance (Table. 1). MICs of these two strains against posaconazole, voriconazole and itraconazole were 0.5 ug/mL, 1 ug/mL and 0.25ug/mL respectively. Table. 1: Aspergillus species distribution and growth on azole resistance screen agar Conclusion(s): We also did not find any azole resistance in this study. Periodic surveillance for the emergence of azole-resistant clinical isolates using molecular approaches is essential.

Melanized (dematiaceous) fungal infections simulating skin cancer in African organ transplant recipients

Fungi are the most frequent skin infections in organ transplant recipients (OTRs) and usually present as superficial mycoses. Deeper infections are much less common, potentially more serious and the incidence is higher in the first few months post-transplant. We report two African OTRs with deep fungal infections caused by dematiaceous (melanized, pigmented or black) fungi, who both presented with suspected skin malignancies. A 60-year-old Nigerian man developed a painful, ulcerated, amelanotic, bleeding nodule on his right fourth toe 2 months after renal transplantation. Clinical differential diagnoses included Kaposi sarcoma (KS), amelanotic acral melanoma and subungual squamous cell carcinoma (SCC). However, histology showed pseudoepitheliomatous hyperplasia, extensive mixed inflammation, multinucleated giant cells and pigmented septate hyphae with rounded 'budding' forms. Periodic acid-Schiff, Grocott and Masson-Fontana stains were positive, and Alcian blue stain was negative, consistent with infection by a dematiaceous fungus. Fungal 18S polymerase chain reaction (PCR) was positive and culture identified Nigrograna mackinnonii. Treatment with oral itraconazole was supervised virtually during the COVID-19 pandemic. After 6 months there was minimal response and he opted for amputation of the digit. A 61-year-old Nigerian man presented 2 months after renal transplantation with a 2-cm diameter nodule on his left thigh at the site of a previous burn. This failed to respond to antibiotics. Magnetic resonance imaging was suggestive of possible malignancy, but surgery was deferred because of the COVID-19 pandemic. Two months later the lesion was 5 cm in diameter and verrucous with an 8-cm sessile, purplish plaque on his right forearm. Atypical KS, lymphoma and chronic burns-associated SCC were all considered. However, histology from both lesions was similar to the first patient. Fungal culture and 18S PCR confirmed infection with the dematiaceous fungus Alternaria alternata. At his request, the right thigh lesion was excised. The lesion on his forearm has partially responded to 8 months of ongoing oral itraconazole. In our African OTR cohort, KS is more common than deep fungal infection. However, despite this suspicion of skin malignancy, both patients had phaeohyphomycoses caused by dematiaceous fungi. Characterized by the presence of melanin in their cell walls, > 130 species of these plant pathogens and soil saprophytes are implicated in human disease, particularly in immunocompromised individuals. Although localized skin diseases (phaeohyphomycoses, chromoblastomycosis and mycetoma) are the most common manifestations, rare disseminated, central nervous system and pulmonary infections may prove fatal. Although uncommon, deep fungal infection should be considered in atypical skin lesions in OTRs;histology, tissue culture and fungal PCR are critical to confirming this diagnosis.

Isolated Colonic Histoplasmosis in Renal Transplant Recipient Post Covid-19 Infection

Introduction: Histoplasmosis is caused by the dimorphic fungus - Histoplasma capsulatum. The presentation of histoplasmosis is often disseminated, though primary intestinal involvement can rarely be seen in patients with cell mediated immune dysfunction like in patients with AIDS. We report a case of renal allograft recipient, who had history of COVID 19 infection and also underwent anti-rejection treatment for renal graft dysfunction, presented with chronic diarrhea and was diagnosed as a case of colonic histoplasmosis. Method(s): We report a case of 45 years old male who underwent renal transplant surgery one and a half year prior (February 2021) and was having stable graft function on tacrolimus, mycophenolate and steroid. He had history of fever and diarrhea in February 2022 and was diagnosed COVID-19 positive with RT-PCR, and was treated conservatively with intravenous dexamethasone and lowering of immunosuppressants. He had mild graft dysfunction in April 2022;renal graft biopsy had acute T-Cell mediated rejection (Banff Grade 1 B) and was treated with pulse steroids for 3 days. He had complaint of intermittent diarrhea, weight loss and intermittent fever since May 2022. He was evaluated and treated on outpatient basis with empirical oral antibiotics. He was admitted in June 2022 with complaint of high grade fever, loose stools leading to hypovolemic shock and renal dysfunction. He had marked thrombocytopenia and neutrophilic leukocytosis. He showed initial response to intravenous broad spectrum antibiotics and crystalloids, but intermittently symptoms of increased stool frequency and altered consistency were still persisting. Stool studies for ova, cyst, parasites and clostridium difficile were negative. Indian ink staining of stool sample had no evidence of Cryptococcosis. Serum PCR for cytomegalovirus was also negative. CT abdomen showed normal visualized bowel and other viscera. Upper GI endoscopy was unremarkable. Colonoscopy revealed multiple small ulcers with erythematous hue and clean base particularly in ceacum and along ascending colon. Multiple colonic biopsies were taken. Histopathology showed lymphoplasmacytic infilterate in the lamina propria. It also showed increased presence of foamy histiocytes, several of which also showed interacellular organism bearing a pseudocapsule. PAS stain also confirmed budding of these interacellular organisms which is consistent with Histoplasmosis. His HRCT chest revealed hyperinflated lungs, cylindrical bronchiectasis in left upper lobe. Urine for histoplasma antigenuria was negative. Result(s): He was treated with intravenous liposomal amphotericin B for initial two weeks followed by oral itraconazole. His symptoms responded remarkably to the treatment. In view of persisting thrombocytopenia and histoplasmosis his mycophenolate was stopped and tacrolimus was titrated as per trough levels Conclusion(s): Colonic histoplasmosis is associated with significant mortatlity and morbidity. Prolonged use of immunosuprresants, use of antirejection therapies (like high dose pulse methyl prednisolone and bortezomib) and even in some case reports COVID 19 infection have shown to increase the risk of histoplasmosis. Primary and isolated colonic histoplasmosis like in this case can be the atypical presentation which emphasizes the importance of maintaining a low threshold for consideration of histoplasmosis in renal allograft recipients. No conflict of interestCopyright © 2023

A case report of a prolonged decrease in tacrolimus clearance due to co-administration of nirmatrelvir/ritonavir in a lung transplant recipient receiving itraconazole prophylaxis.

BACKGROUND: Drug-drug interaction management is complex. Nirmatrelvir/ritonavir is a potent cytochrome P450 (CYP) 3A inhibitor and influences pharmacokinetics of co-administered drugs. Although there are several reports about drug-drug interactions of nirmatrelvir/ritonavir, an influence of a concomitant use of nirmatrelvir/ritonavir and another potent CYP3A inhibitor on tacrolimus remains unclear. Here, we experienced a lung transplant patient with the novel coronavirus disease 2019 (COVID-19). In this patient, nirmatrelvir/ritonavir was administered, and the inhibitory effect of itraconazole on CYP3A was prolonged. CASE PRESENTATION: We present a case in forties who had undergone lung transplantation. He was administered itraconazole and tacrolimus 1.0 mg/d, with a trough value of 8-12 ng/mL. The patient contracted the COVID-19, and a nirmatrelvir/ritonavir treatment was initiated. During the antiviral treatment, tacrolimus administration was discontinued for 5 d. Tacrolimus was resumed at 1.0 mg/d after completion of the nirmatrelvir/ritonavir treatment, but the trough value after 7 d was high at 31.6 ng/mL. Subsequently, the patient was placed on another 36-h tacrolimus discontinuation, but the trough value decreased to only 16.0 ng/mL. CONCLUSIONS: Co-administration of ritonavir caused a prolonged decrease in tacrolimus clearance through its inhibitory effects on CYP3A in a patient taking itraconazole. Management of drug-drug interaction by pharmacists can be important for patients with multiple medications.

White piedra: An uncommon cause of pseudonits in Northeast Mexico

Introduction: White piedra is a rare superficial mycosis caused by the genus Trichosporon. Its prevalence is higher among tropical climates and predominantly affects children and women. Less than 17 cases have been described in Mexico, none of them in the Northeast region. We present the first case reported in this zone. Case presentation: A 27-year-old otherwise healthy woman presented to our clinic with a 1-month history of asymptomatic pseudonits on her scalp hair. Physical evaluation revealed numerous small white concretions over the majority of the hair shafts. At trichoscopic inspection, multiple white-yellowish ovoid nodules were observed. Direct microscopic examination with 20% potassium hydroxide (KOH) and blue cotton showed nodules composed of arthroconidia and hyphae over the hair shaft. Additionally, fungal culture was positive for Trichosporon inkin, confirming the diagnosis of white piedra. Treatment was initiated with ketoconazole shampoo and systemic itraconazole with favorable response. Discussion(s): Since the first case description by Beigel in Germany, most white piedra cases have been reported in tropical and humid climates. This mycosis typically affects females and subjects under 15 years of age. Some risk factors include poor hygiene, excess humidity, diabetes, and long, curly hair. In our case, the patient had curly hair and she constantly tied her hair up wet as she worked as a full-time nurse in a COVID-19 reference center. In our country, 50% of previous reported cases are from nontropical regions. Although infrequent in cosmopolitan areas in Northeast Mexico, white piedra should be considered in the differential diagnosis of pseudonits. Copyright © 2022

DISSEMINATED HISTOPLASMOSIS IN THE SETTING OF IMMUNOSUPPRESSION DUE TO CROHN DISEASE

SESSION TITLE: Critical Gastrointestinal Case Reports SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Histoplasma capsulatum is a dimorphic fungus most commonly encountered as an opportunistic infection in immunosuppressed patients, particularly those with HIV/AIDS. However, patients immunosuppressed from other causes can also be at risk. Here is presented the case of a patient on multi-immunosuppressant therapy as treatment for Crohn's disease, who developed disseminated histoplasmosis. CASE PRESENTATION: A 44-year-old male with a past medical history of Crohn's disease (previously been on azathioprine, adalimumab and currently on Prednisone therapy), recently started on infliximab infusion for uncontrolled symptoms of IBD, diabetes mellitus, hypothyroidism, and COVID-19 infection (not requiring oxygen therapy) one month prior to the current admission initially presented to the hospital with chief complaints of exacerbated weakness, myalgias, fevers and diarrhea for 5 days;Symptoms of weakness, myalgias began after first infusion of infliximab and it got progressively worse after the 2nd infusion 2 weeks prior to the admission. White Blood Cell count was 1.1 K/uL, platelet count was 7 K/uL, hemoglobin was 7.9 g/dL. CRP was elevated to 142 mg/L, and ferritin was elevated to 39,000 ug/L. CT abdomen and pelvis demonstrated probable rectosigmoid colitis and splenomegaly. Subsequent chest x-ray demonstrated bilateral opacities with haziness over bilateral lung fields. Respiratory viral panel, stool panel, blastomyces antigen, cryptococcal antigen, toxoplasma antibodies, HIV antibody, CMV PCR, and blood cultures were unrevealing. Urinary histoplasma antigen was positive, and BD-glucan was elevated to over 500 ng/L. EBV panel was positive for reactivation, with EBV DNA 2.02 IU/mL. He was subsequently started on amphotericin B lipid complex, with itraconazole destination therapy. He was treated empirically for pneumocystis jiroveci pneumonia (PJP) with sulfamethoxazole-trimethoprim due to him being on chronic Prednisone therapy. Echocardiogram demonstrated left ventricular ejection fraction (LVEF) of 40%, with diffuse hypokinesis and wall motion abnormalities, posing some question of myocarditis. He was later discharged home in an improved state. DISCUSSION: Disseminated histoplasmosis in the setting of Crohn's disease on chronic immunosuppressive therapy has been very rarely reported,(1) with similar reports in patients on immunosuppressive therapy in the setting of rheumatologic disease being slightly more common.(2) The most commonly involved areas in gastrointestinal histoplasmosis are the terminal ileum and colon,(3) with this patient's rectosigmoid colitis and symptomatology being consistent with this pattern. The patient's myocarditis is also consistent with disseminated histoplasmosis infection. CONCLUSIONS: Clinicians should maintain suspicion for opportunistic infections in patients on immunosuppressive therapy in the setting of critical illness. Reference #1: Bhut, B., Kulkarni, A., Rai, V. et al. A rare case of disseminated histoplasmosis in a patient with Crohn's disease on immunosuppressive treatment. Indian J Gastroenterol 37, 472–474 (2018). https://doi.org/10.1007/s12664-018-0886-1 Reference #2: Wood KL, Hage CA, Knox KS, et al. Histoplasmosis after treatment with anti-tumor necrosis factor-alpha therapy. Am J Respir Crit Care Med. 2003;167(9):1279-1282. doi:10.1164/rccm.200206-563OC Reference #3: Galandiuk S, Davis BR. Infliximab-induced disseminated histoplasmosis in a patient with Crohn's disease. Nat Clin Pract Gastroenterol Hepatol. 2008;5(5):283-287. doi:10.1038/ncpgasthep1119 DISCLOSURES: no disclosure on file for Donald Dumford;No relevant relationships by Abhilash Bhat Marakini No relevant relationships by Palak Rath No relevant relationships by Sterling Shriber

DISSEMINATED BLASTOMYCOSIS FOLLOWING COVID-19 INFECTION

SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: The diagnosis of blastomycosis is often delayed due to its non-specific symptoms and imaging findings. Clinicians must have a high clinical index of suspicion to diagnose blastomycosis in a timely manner, especially in the setting of the current COVID-19 pandemic. CASE PRESENTATION: A healthy 44-year-old male presented to an urgent care center with complaints of cough, fevers, and malaise. CT scan of the chest revealed a left upper lobe mass concerning for rounded bacterial pneumonia versus malignancy. He was found to be COVID-19 positive. The patient was sent home with steroids and antibiotics. Three months later, a repeat CT scan of the chest was obtained which revealed progression of the consolidation and prompted further evaluation at the hospital. On presentation, he reported a persistent cough, weight loss, and the development of multiple painful nodules on his extremities and trunk within the past week. A skin lesion was biopsied. A bronchoscopy was also performed for biopsy and brushing. Biopsy of the skin lesion as well as specimens collected from the bronchoscopy resulted positive for Blastomyces. MRI of the brain demonstrated multiple enhancing lesions concerning for septic emboli. He was started on amphotericin B for treatment of disseminated blastomycosis with central nervous system (CNS) involvement. Repeat imaging of the brain and chest about 3 weeks after initiation of therapy showed interval decrease in the size of the lesions. He was then transitioned to oral itraconazole and discharged home. DISCUSSION: Blastomycosis is an endemic fungal infection that can affect immunocompetent and immunocompromised hosts. It tends to infect immunocompetent hosts more so than other invasive fungal infections. Symptoms can range from asymptomatic to rapidly progressive acute respiratory distress syndrome (ARDS). Disseminated blastomycosis has been reported in 20-50% of patients (1). In the above case, an immunocompetent patient developed pulmonary and dermatologic manifestations concerning for disseminated blastomycosis. Though he had no recent travel, occupational exposures, or contact with any construction work, the patient was living in an endemic area for Blastomyces. It is difficult to definitively ascertain if the patient already had pulmonary blastomycosis when he was diagnosed with COVID-19, but his extrapulmonary manifestations clearly developed after the diagnosis. Earlier detection and treatment of the pulmonary blastomycosis may have prevented the dissemination of the disease. CONCLUSIONS: This case serves as a reminder to consider other infectious etiologies, like endemic fungal infections, in the midst of the COVID-19 pandemic to prevent delays in treatment and progression of these diseases. Reference #1: McBride JA, Gauthier GM, Klein BS. Clinical Manifestations and Treatment of Blastomycosis. Clin Chest Med. 2017 Sep;38(3):435-449. doi: 10.1016/j.ccm.2017.04.006. Epub 2017 Jun 12. PMID: 28797487;PMCID: PMC5657236. Reference #2: Cafardi J, Haas D, Lamarre T, Feinberg J. Opportunistic Fungal Infection Associated With COVID-19. Open Forum Infect Dis. 2021 Jan 18;8(7):ofab016. doi: 10.1093/ofid/ofab016. PMID: 34621913;PMCID: PMC7928619. DISCLOSURES: No relevant relationships by Shannon Burke No relevant relationships by Abigail Go No relevant relationships by Jen Minoff No relevant relationships by David Stoeckel

SUBACUTE PULMONARY HISTOPLASMOSIS DISGUISED AS COVID-19 IN A HEALTHY YOUNG MALE

SESSION TITLE: Pathology Identifying Chest Infections Case Report Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Pulmonary histoplasmosis typically affects immunocompromised individuals. Symptomatic infection in immunocompetent patients is rare, however, important risk factors include living in an endemic region and the size of inoculation. We present a case of subacute pulmonary histoplasmosis in a healthy young male and discuss how availability bias during the COVID-19 pandemic may pose challenges in the diagnosis. CASE PRESENTATION: A healthy 30-year-old male presented to our hospital complaining of left flank and bilateral chest pain for one week. The patient returned from Veracruz, Mexico three weeks prior after spending two months there studying to become a chef. While in Mexico, the patient experienced low-grade fevers, night sweats, and pleuritic chest pain for which he was treated with steroids and antibiotics for presumed COVID-19 infection despite negative testing. Treatment provided the patient temporary relief, however, some of his symptoms returned prompting him to present to the emergency department. Upon presentation, the patient was afebrile and had a normal resting pulse oximetry. CT angiogram of the chest demonstrated three lung nodules and prominent mediastinal lymphadenopathy. A complete infectious and rheumatologic workup was performed. BAL, transbronchial biopsies and EBUS-TBNA were performed. Lung biopsy showed reactive pneumocytes, focal intra-alveolar fibrinous material, congestion, and hemorrhage. Lymph node cytology revealed an aggregate of necrotizing and nonnecrotizing granulomas and GMS stain was positive for yeast. Fungitell and Histoplasma antibodies returned positive. The patient was discharged on Itraconazole and followed up with infectious disease specialists two months later in stable condition. DISCUSSION: Patients with subacute pulmonary histoplasmosis and viral pneumonia may present with similar clinical and radiological findings making the diagnosis arduous. In addition, the prevalence of COVID-19 pneumonia makes clinicians susceptible to using availability bias and further obscuring diagnosis. Some clues that help differentiate subacute pulmonary histoplasmosis include a longer duration of symptoms, pulmonary nodules, and mediastinal and hilar adenopathy. CONCLUSIONS: While pulmonary histoplasmosis is an uncommon finding in immunocompetent patients, suspicion should be raised in patients from endemic regions. Despite the COVID-19 pandemic, clinicians should avoid anchoring biases and keep differential diagnoses in mind. Reference #1: Azar MM, Hage CA. Clinical Perspectives in the Diagnosis and Management of Histoplasmosis. Clin Chest Med. 2017;38(3):403-415. doi:10.1016/j.ccm.2017.04.004 Reference #2: Staffolani S, Buonfrate D, Angheben A, et al. Acute histoplasmosis in immunocompetent travelers: a systematic review of literature. BMC Infect Dis. 2018;18(1):673. Published 2018 Dec 18. doi:10.1186/s12879-018-3476-z DISCLOSURES: No relevant relationships by Steven Douedi No relevant relationships by Justin Ilagan No relevant relationships by TAIMOOR KHAN No relevant relationships by Romany Nightingale No relevant relationships by Mihir Odak No relevant relationships by Noor Salam No relevant relationships by Kameron Tavakolian

SEVERE PULMONARY BLASTOMYCOSIS IN A PATIENT WITH A COVID-19-POSITIVE TEST: A DANGEROUS ANCHORING BIAS

SESSION TITLE: Severe and Unusual Blastomycosis Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 12:25 pm - 01:25 pm INTRODUCTION: Severe pulmonary blastomycosis (PB) usually affects immunocompromised patients, with very high mortality rate of up to 40%. PB can mimic pneumonia caused by other organisms (1), which can delay diagnosis and treatment initiation. We present a case of severe PB that was initially thought to be COVID-19 pneumonia, to our knowledge this is 2nd case of concomitant PB and COVID-19 infection in literature. (2) CASE PRESENTATION: Patient is 52 year old female with past medical history of atrial fibrillation, asthma, bariatric surgery, that presents with shortness of breath for 2 weeks. Despite receiving only 1 dose of COVID-19 vaccine (Moderna) 5 months ago, patient tested positive for COVID-19 on PCR test at the urgent care 4 days prior. Her symptoms progressed despite initial outpatient treatment with steroids and antibiotics. Initial emergency department chest computed tomography (CT) revealed dense bilateral consolidations, with hypoxic respiratory failure, patient was admitted for treatment of presumed COVID-19 pneumonia, and guideline directed treatment was initiated. Despite maximal medical management, that included steroids, broad spectrum antibiotics, remedisivir, patient failed to improve, with repeat CT chest revealing worsening consolidations. Bronchoscopy was performed 12 days into the admission revealed thick white secretions, with cultures growing blastomyces dermatitidis. At this point patient development of septic shock with multiorgan failure. Patient was subsequently intubated, and due to significant renal failure, initiated on hemodialysis (HD). Anti-fungal treatment was initiated with amphotericin B, and transitioned to itraconazole afterwards. Patient required several HD sessions, after which her renal function fully recovered. Patient was successfully extubated 7 days later, but required additional 22 days of medical care and physical therapy before being ready for discharge to rehabilitation facility. On the outpatient follow up 6 weeks after discharge, patient continues to slowly recover. Repeat CT chest still with significant bilateral consolidations. Patient will require at least 12 months of itraconazole therapy. DISCUSSION: PB can mimic bacterial and viral pneumonia symptoms. (1) In the widespread COVID-19 pandemic, clinicians can be misled by COVID-19 positive test in patient with bilateral pneumonia, and initiate guideline directed therapy. Immunosuppression agents can lead to adverse outcomes in patients with underlying PB. Questionable is the significance of COVID positive PCR test in semi-vaccinated individual. Potentially even mild COVID-19 infection could predispose patient for PB. Early diagnosis of PB is important, as delay in treatment and medical immunosuppression can lead to worse outcomes. CONCLUSIONS: PB should be suspected even in patients presenting with positive COVID-19 PCR test. Guideline directed therapy for COVID-19 can worsen underlying PB. Reference #1: https://www.cdc.gov/fungal/covid-fungal.html Reference #2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8503152/ DISCLOSURES: No relevant relationships by Dovile Baniulis No relevant relationships by Dovile Cerkauskaite No relevant relationships by Igor Dumic No relevant relationships by Momcilo Durdevic No relevant relationships by Dragana Durdevic No relevant relationships by Ashutossh Naaraayan No relevant relationships by Ankita Subedi

Chronic Pulmonary Aspergillosis During Convalescence From Severe COVID-19 Treated With Oral Itraconazole: A Report of Two Cases.

Invasive pulmonary aspergillosis (IPA) has been reported to occur secondary to coronavirus disease 2019 (COVID-19), and the condition has been termed COVID-19-associated pulmonary aspergillosis (CAPA). We diagnosed two severe COVID-19 cases with multiple cavitary lung lesions and chronic pulmonary aspergillosis (CPA) on days 58 and 48 of admission, respectively, with gradual improvement in the respiratory status. Both patients were positive for Aspergillus-precipitating antibodies (APAb). We chose oral itraconazole (ITCZ) for both patients because of its convenience in terms of long-term treatment. Cavitary lesions diminished after ITCZ administration. The risk factors for pulmonary aspergillosis in both patients were determined to be steroid pulse therapy, use of baricitinib, diabetes mellitus (DM), ICU admission, long hospital stay, and the use of broad-spectrum antibiotics. Pulmonary aspergillosis must be suspected in patients with severe COVID-19, even if they are asymptomatic, because not only IPA but also CPA can occur following COVID-19. Therefore, oral ITCZ may be a treatment option for CPA following COVID-19.

Perioperative Concerns for Patients with Prior SARS-CoV-2 Infection: Our Experience

Methodology and case description: Case 1: A 55-year-old hypertensive male with complaints of chest pain presented to the cardiology department. He underwent angiography to reveal triple vessel disease and was scheduled for coronary artery bypass graft surgery. During preoperative evaluation, patient gave a history of having suffered from mild COVID-19, getting cured with conservative management under home isolation 3 months back. Examination revealed bilateral basal crepitations. Chest X-ray was indicative of fibrosis basal areas of both lungs (right > left) which was confirmed by HRCT chest. Preoperatively the patient was optimised with antifibrotic agent nintedanib and methylprednisolone. He was reviewed after 1 month and had shown significant-resolution radiologically as well as clinically (improved breath holding time, saturation and lung auscultation). Intraoperative course was uneventful and the patient was ventilated with low tidal volume. Postoperatively, the patient was extubated on day 1. Patient experienced difficulty in expectoration which was improved by N-acetyl cysteine administered intravenously and via nebulisation along with active vigorous physiotherapy. Patient was discharged on the 7th postoperative day. Case 2: A 37-yearold female, a known case of severe mitral stenosis, moderate pulmonary hypertension, moderate tricuspid regurgitation was under conservative management with diuretics and beta-blockers and was being planned for mitral valve replacement. The patient had developed COVID-19 infection 1 month back and was treated under home isolation and conservative management. However, the patient presented with an increase in exercise intolerance post COVID infection. Suspecting the possibility of fluid overload/ heart failure and pulmonary hypertension, the diuretic dose was increased post admission, but to no avail. Chest X-ray and HRCT chest were done which highlighted the possibility of allergic bronchopulmonary aspergillosis;which has been described as one of the rare findings coexisting with active COVID-19 infection. This was confirmed by the serum IgE levels and presence of eosinophilia in the complete blood picture. The patient was initiated on itraconazole and methylprednisolone which resulted in improvement in breathlessness over the next 3 weeks. The patient was subsequently posted for surgical replacement of the mitral valve. Intra-operative and post-operative course was uneventful and the patient was discharged on 5th post-operative day. Conclusion: These 2 cases who had suffered from mild COVID-19 infection presented significant challenges for safe intra- and post-operative conduct of anaesthesia. These challenges were overcome by efficient prehabilitation and optimisation of the patient and optimal post-operative critical care. Intra-operative course is often just a small segment of the overall hospital course of the patient and the role of critical care in the pre-surgical, extra-hospital care along with post-operative care needs acknowledgement and recognition.

A Case of Multifocal Necrotizing Blastomycosis Pneumonia and Acute Respiratory Distress Syndrome (ARDS) in an Adolescent with Type 1DiabetesMellitus

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.

Filamentous fungi associated with COVID-19 and its susceptibility to some antifungals

The purpose of this study was to conduct a survey of the fungal species associated with COVID-19 viral infection in 150 patients who were admitted to the intensive care unit (ICU) in Al-Diwaniyah Teaching Hospital in Al-Diwaniyah City, Iraq, for a period of five months beginning in October 2021 and ending in February 2022. The survey was to be conducted over the course of the period from October 2021 to February 2022. According to the findings, yeasts were more prevalent than any of the other detected fungal species, accounting for 98 of the total isolates (65.33 percent). While filamentous fungus accounted for 19 isolates (12.33 percent), including the predominance of Aspergillus flavus with 6 isolates (40 percent) in comparison to the Aspergillus spp. ratio, these fungi were found to be rather uncommon. In light of the fact that this publication provided evidence of the isolation of Aspergillus sydowii from COVID19 patients for the first time anywhere in the world: In addition, we drew attention to the outstanding activity of the antifungal medications amphotericin B, itraconazole, and voriconazole, all of which have a high susceptibility rate. © 2022 International Journal of Health Sciences.All rights reserved.

Clinical characteristics and factors influencing development of a pulmonary fungal infection in patients with severe respiratory diseases

Objectives: To examine the clinical characteristics, drug resistance, and factors influencing development of a pulmonary fungal infection in patients with severe respiratory diseases in order to provide a reference for clinical treatment.

American Society for Clinical Pharmacology and Therapeutics - 123rd Annual Meeting. Virtual - March 16-18, 2022

The 2022 American Society for Clinical Pharmacology and Therapeutics (ASCPT) Annual Meeting held virtually, with "Disruptive innovation" as the motto, offered attendees an outstanding scientific program focused on clinical pharmacology, translational medicine, drug discovery and drug development. It is the most important event for scientists involved in clinical pharmacology and translational medicine. The ASCPT conference offers scientists from different professional scopes and around the world the perfect opportunity to discuss emerging science. It focuses on improving the understanding and use of existing drug therapies and developing safer and more effective treatments for the future. Oral and poster presentations were available for participants during the running of the conference to accommodate the different time zones. Presentations covered the latest research with the option to ask questions after each presentation via a chat function. Discussion boards were available to provide networking opportunities for virtual attendees.