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Case Report: Cryptococcosis is an opportunistic infection caused by the encapsulated yeast Cryptococcus, with C. neoformans and C. gattii being the most common species to cause human disease. Immunocompromised individuals are predisposed to infections with C. neoformans, which has known predilection to CNS and pulmonary lymph nodes. We present a unique case of disseminated cryptococcosis in the setting of end-stage renal disease (ESRD), cirrhosis, tumor necrosis factor inhibitor use and steroid use for COVID19. Method(s): A single-patient case report was conducted after IRB approval. Case Presentation: A 55-year-old woman with uncontrolled diabetes, lupus, rheumatoid arthritis on adalimumab, hepatitis C status post boceprevir, cirrhosis, former IV drug use, and ESRD on hemodialysis via bovine arterial-venous fistula graft presented with worsening dyspnea, cough, and altered mental status. Three months prior, patient was admitted to an outside hospital for COVID19, complicated by pulmonary embolism status post anticoagulation therapy. Patient was treated with an unknown steroid regimen, which was continued by a second outside facility when symptoms failed to improve. Patient then presented to our facility 24 hours after discharge due to continued symptoms. On admission, patient was noted to have altered mentation and hypoxia with pulmonary edema on chest x-ray and was urgently hemodialyzed. Further work-up was obtained due to non-resolving symptoms, including blood and sputum cultures, cocci serology and QuantiFERON gold. CT chest revealed bilateral consolidations. Patient was started on antibiotics for presumed hospital-acquired pneumonia. During the hospital stay, preliminarily blood cultures grew yeast and patient was started on Micafungin. However, Micafungin was changed to Liposomal Amphotericin B as ovoid structures seen on gram stain could not confirm nor rule out cryptococcus. Subsequent bronchial wash and bronchoalveolar lavage cultures, as well as final blood cultures resulted Cryptococcus neoformans. Serum cryptococcus antigen returned reactive, titer 1:512. Antibiotics were discontinued and Isavuconazonium was started with Liposomal Amphotericin B. Due to recurrent headaches, lumbar puncture was obtained and revealed lymphocytic pleocytosis without cryptococcal antigenicity. Patient completed 14 days of Liposomal Amphotericin B and Isavuconazole with continuation of Isavuconazole upon discharge. Conclusion(s): Disseminated cryptococcosis in non-HIV patients is rare in the modern HIV era. Clinicians should be aware and include it in their differential of any patient with multiple risk factors for opportunistic infection. In patients with cirrhosis and ESRD, treatment is limited given altered pharmacokinetics. Studies have shown improved survival with the addition of Isavuconazole in patients with disseminated cryptococcosis with CNS involvement in the setting of chronic liver disease and ESRD.
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The 2021 Conference on Retroviruses and Opportunistic Infections (CROI) featured a timely review of the neurologic complications of COVID-19 as well as new research findings on mechanisms by which SARS-CoV-2 may affect the brain. CROI included new and important findings about the neurologic complications of HIV-1, human polyomavirus 2 (also known as JC Virus), and cryptococcus. New long-term analyses of cognition in people with HIV-1 identified that cognitive decline over time is associated with multimorbidity, particularly diabetes, chronic lung disease, and vascular disease risk conditions. These conditions are associated with aging, and the question of whether people with HIV are at risk for premature aging was addressed by several reports. New findings from large analyses of resting state networks also provided valuable information on the structural and functional networks that are affected by HIV-1 infection and cognitive impairment. Several reports addressed changes after initiating or switching antiretroviral therapy (ART). Findings that will improve understanding of the biologic mechanisms of brain injury in people with HIV were also presented and included evidence that host (eg, myeloid activation, inflammation, and endothelial activation) and viral (eg, transcriptional activity and compartmentalization) factors adversely affect brain health. Other research focused on adjunctive therapies to treat HIV-1 and its complications in the central nervous system. This summary will review these and other findings in greater detail and identify key gaps and opportunities for researchers and clinicians.Copyright © 2021, IAS-USA. All rights reserved.
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Case Report: Over 90% of cases of cryptococcal meningoencephalitis present in immunocompromised patients, with the majority of those being in patients with AIDS. However, this infection can also occur in patients with other immunocompromised states, such as steroid use, malignancy, rheumatologic diseases, and use of immunosuppressive medications. Delay in diagnosis can often lead to rapid neurological deterioration and mortality. Case: A young, otherwise immunocompetent patient, with a history of Chiari I malformation and recent COVID- 19 infection presented with syncope following two weeks of headaches, generalized body aches and weakness after COVID-19 diagnosis. Physical exam demonstrated an isolated CN VI palsy. Head imaging revealed new right caudate infarcts, and a cerebellar tonsillar descent compatible with history of Chiari I malformation. Initial lumbar puncture (LP) was deferred due to congenital brain herniation. Over the next few days, the patient continued to show increasing neurological deficits such as truncal ataxia and increased mood instability. The patient was transferred to the Intensive Care Unit, and LP was obtained under special neuro-critical care direction. Due to increased opening pressures and yeast on gram stain, cryptococcus was suspected and later confirmed. Although anti-fungal therapy was initiated, the patient continued to deteriorate, leading to cardiac arrest, intubation, and placement of lumbar drain. The patient unfortunately did not demonstrate neurologic recovery following arrest and progressed to brain death. Discussion(s): While cryptococcal meningoencephalitis is overwhelmingly a disease of immunocompromised patients, it can occur in immunocompetent hosts, and delay in diagnosis and treatment can lead to adverse and fatal outcomes. This patient had no known underlying conditions besides a recent mild COVID-19 infection and underlying Chiari I malformation, neither of which are known to be associated with cryptococcal meningoencephalitis. These factors may however have played a role in his disease and progression. Copyright © 2023 Southern Society for Clinical Investigation.
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The proceedings contain 542 papers. The topics discussed include: risk factors associated with oropharyngeal candidiasis in COVID-19 patients: a case control study;diagnosis of fungal infections in animals: combining the old and the new to maximize results;genetics andgenomics of Malassezia species;diversity and hybridization in Malassezia furfur;the human pathobiont Malassezia furfur secreted protease MFSAP1 regulates cell dispersal and exacerbates skin inflammation;challenges in diagnosing and management of invasive fungal infections during the pandemic;Cryptococcus QPCR assays: the future for routine mycology labs and clinical trials dealing with cryptococcosis;epidemiology of myotic keratitis in developing countries;proteomics in fungal keratitis research: a road map to personalized treatment;incidence of mixed fungal infections in post-COVID-19 outbreak of mucormycosis;talaromycosis in HIV-negative patients: challenges and counter-measures;and evaluation of new tools for the diagnosis of histoplasmosis.
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SESSION TITLE: Uncommon Presentations and Complications of Chest Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Cryptococcus is a ubiquitous fungus in the environment. Infections can occur in humans when Cryptococcus is aerosolized and inhaled. Severity of clinical presentation varies from asymptomatic pulmonary colonization to disseminated life-threatening infection such as meningitis. These infections usually occur with deficiencies in T-cell-mediated immunity, including those with HIV/AIDS and immunosuppression due to transplantation. Herein we present a case of isolated pulmonary cryptococcosis in an immunocompetent host. CASE PRESENTATION: The patient is a 36-year-old never-smoker male with history of recurrent left spontaneous pneumothorax status post VATS blebectomy, negative for alpha-1 antitrypsin deficiency and cystic fibrosis. A year later, he presented with fatigue, shortness of breath, and dry cough after a recent trip to Ohio. Viral panel including COVID-19 was negative. A chest x-ray showed a new 4 cm rounded opacity in the right middle lobe (RML). A CT scan of the chest showed 2 mass-like and nodular areas of consolidation with surrounding GGOs within the RML (Figure 1). He underwent navigational bronchoscopy with transbronchial biopsy (TBBx) of RML, BAL, and EBUS with transbronchial needle aspiration (TBNA). Cytology was negative for malignant cells. BAL showed rare yeast. Pathology of the TBBx showed the airway wall with chronic inflammation including granulomatous inflammation, positive for yeast, most consistent with Cryptococcus with positive Grocott methenamine silver (GMS) stain (Figure 2). Culture of the TBNA grew C. neoformans var. grubii. Other cultures were negative. Serum Cryptococcal antigen was positive. HIV test was negative. He started treatment with oral fluconazole with improvement of symptoms. DISCUSSION: Clinical presentation of pulmonary cryptococcosis can include a variety of symptoms in which immune status is critical for determining the course of infection. Infection can vary from asymptomatic infection to severe pneumonia and respiratory failure, and meningitis. Similarly, imaging findings can also vary and be characterized as pulmonary nodules, consolidations, cavitary lesions, and/or a diffuse interstitial pattern. The diagnosis of Cryptococcus is made using histology, fungal cultures, serum cryptococcal antigen, and radiography in the appropriate clinical and radiological context. Treatment recommendations are determinant on immune status of the patient as well as symptoms. Asymptomatic and localized disease in immunocompetent patients can be monitored and mild/moderate disease can be treated with fluconazole. Those with severe or disseminated infection warrant induction therapy with an amphotericin B and flucytosine CONCLUSIONS: Clinical and radiological presentation of cyptococcosis varies depending on immune status. Disease can occur in both immunocompromised and competent hosts. Immune status determines disease course and treatment. Reference #1: Huffnagle GB, Traynor TR, McDonald RA, Olszewski MA, Lindell DM, Herring AC, et al. Leukocyte recruitment during pulmonary Cryptococcus neoformans infection. Immunopharmacology. 2000 Jul 25;48(3):231–6. Reference #2: Kd B, Jw B, Pg P. Pulmonary cryptococcosis. Semin Respir Crit Care Med [Internet]. 2011 Dec [cited 2022 Apr 2];32(6). Available from: https://pubmed.ncbi.nlm.nih.gov/22167400/ Reference #3: Ms S, Rj G, Ra L, Pg P, Jr P, Wg P, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am [Internet]. 2000 Apr [cited 2022 Apr 1];30(4). Available from: https://pubmed.ncbi.nlm.nih.gov/10770733/ DISCLOSURES: No relevant relationships by Mina Elmiry No relevant relationships by Brenda Garcia No relevant relationships by Zein Kattih no disclosure on file for Priyanka Makkar;No relevant relationships by Jonathan Moore
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SESSION TITLE: COVID-19: Other Considerations in Management SESSION TYPE: Original Investigations PRESENTED ON: 10/18/2022 02:45 pm - 03:45 pm PURPOSE: To evaluate the incidence of fungal co-infections clinical characteristics, and outcomes in patients with COVID-19. METHODS: We conducted a retrospective chart review of electronic medical records of 2,639 adult patients admitted for COVID -19 to our health system from April 1, 2020 to December 31, 2021. Demographic data, comorbidities, length of hospital stay, laboratory results including fungal diagnostics, COVID therapeutics and antifungals, need for ICU admission, mechanical ventilation and in-hospital mortality were collected. RESULTS: A total of 45 of 2,639 (1.7%) COVID-19+ patients had a positive fungal test or culture of fungal pathogen and subsequently received antifungal treatment. Of these 25 (55.6%) cases of Aspergillus species were the most prominent, followed by Candida species at 12 (26.7%). Of note, there was one case each of Cryptococcus and Histoplasma (2.2%). COVID-19+ patients with fungal co-infection who survived (18;40%) were significantly younger compared to COVID-19+ patients with fungal co-infection who died (27;60%, p=0.014). Majority of COVID-19+ patients with fungal co-infection were white with average length of hospitalization of 24 days. Those patients who survived had a significantly longer length of hospitalization compared to COVID-19+ patients who died (survived 31 ± 21.5 compared to 19.6 ± 10.4 days, p<0.05). Majority of COVID-19+ patients received steroids, and remdesivir therapy for COVID-19. Antifungal treatment consisted of either voriconazole or micafungin as predominate fungal pathogens were either Aspergillus or Candida spp. CONCLUSIONS: Pulmonary aspergillosis followed by invasive candidiasis were the most common fungal co-infections in COVID-19 patients treated at our institution. In-hospital mortality from all fungal co-infections was 60%. Patients that survived were younger and hospitalized longer compared to those who expired. Need for mechanical ventilation, ICU admission and COVID therapeutics were not significantly different between the survived and expired group of COVID-19 patients with fungal co-infections. CLINICAL IMPLICATIONS: The increased risk and incidence of COVID-19 and fungal co-infection has been noted in a handful of studies with invasive aspergillosis being the most commonly reported fungal co-infection. There have been very few reports of other fungal co-infections including invasive candidiasis, mucormycosis, histoplasmosis, and cryptococcosis. Minimal incidence data has been reported on co-infection with other opportunistic fungal pathogens such as Histoplasma spp., Pneumocystis jirovecci, or Cryptococcus neoformans. This study supports previous findings of increase risk of Aspergillosis, but also show incidence of Histoplasmosis and Crytpococcal fungal infections. These fungal infections may be under reported in COVID-19 and may warrant further research. DISCLOSURES: No relevant relationships by Christopher Destache No relevant relationships by Rutendo Jokomo-Nyakabau No relevant relationships by Dorothy Kenny No relevant relationships by Paul Millner No relevant relationships by Anny Nguyen No relevant relationships by Mohammad Selim No relevant relationships by Richard Swaney No relevant relationships by Manasa Velagapudi
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BACKGROUND: COVID-19 has increased awareness of fungal infections among hospitalized patients. With the use of multiple immune-modulating drugs in COVID-19 along with COVID-19 related immune suppression, the risk of fungal infections is high. We studied fungal infections in COVID-19 to identify patterns to aid in preventive measures. METHODS: We included all COVID-19 positive adult patients (≥18 years) hospitalized between March 1, 2020, to October 1, 2021. Fungal infections were deemed positive if they developed fevers, leukocytosis along with positive cultures (blood, respiratory or urine). Candida albicans was considered to be causative if either blood cultures were positive or positive cultures from 2 sites and antifungals were administered. Outcomes studied were rates, organisms involved, and in-hospital mortality. We used multivariable logistic regression models to examine characteristics associated with the development of fungal infections. Variables used in the model included patient demographics (age, gender, race), comorbidities (congestive heart failure, diabetes mellitus, chronic obstructive pulmonary disease, end- stage renal disease, cirrhosis, and cancer), medications used to treat COVID-19 (ivermectin, hydroxychloroquine, steroids, tocilizumab, baricitinib), the severity of disease (4C score, use of invasive mechanical ventilation (IMV), acute kidney injury (AKI) requiring hemodialysis), and presence of central venous catheters. RESULTS: Of 7508 admissions with COVID-19, 82 (1.1%) acquired fungal infections. Fungal infections developed in 61(3.7%) of the 1642 intensive care unit (ICU) admissions and 21 (0.4%) of the 5866 non-ICU admissions. Among the fungal infections - 33 were Candida albicans, 28 were non-candida albicans, 19 were molds and 2 were cryptococcus. Fungal infections were associated with the use of IMV (Odds Ratio (OR) 13.3, 95% confidence interval (CI) 6.7-26.3, p<0.001), steroids (OR 2.4, 95%CI 1.6- 3.6, p<0.001), and AKI requiring hemodialysis (OR 2.2, 95%CI 1.2-4.1, p=0.01). Of the 5866 non-ICU admissions, in-hospital mortality was significantly higher in those with fungal infections (65% vs 7.3%, p< 0.001). Similarly, among the 1642 ICU admissions, in-hospitalmortality was significantly higher in those with fungal infections (64% vs 37%, p<0.001). On logistic regression analysis, fungal infections were associated with higher in-hospital mortality (OR 2.0;95%CI 1.1- 3.6, p=0.03). Of the fungal infections, molds were associated with higher in-hospital mortality (OR 4.4, 95%CI 1.2- 16.4) while Candida albicans (OR 2.4, 95%CI 0.9-6.4, p=0.08) and non-albicans candida (OR 1.2, 95%CI 0.5-3.3, p=0.66) did not reach significance. CONCLUSIONS: Fungal infections are rare in hospitalized COVID-19 patients but ten times more common in ICU admission. Fungal infections were associated with IMV, steroids, and AKI requiring hemodialysis. Molds were associated with higher in-hospital mortality.
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Introduction / Case Presentation:46yo female with a history of CKD, atrial flutter, bioprosthetic valve with mitral ring, and recent COVID-19 pneumonia who presented to the emergency department (ED) with shortness of breath, fevers, and fatigue. Three months prior, she had been diagnosed with severe COVID-19 pneumonia, for which she received dexamethasone, remdesivir, tocilizumab, anakinra, and IVIG. She was discharged to a nursing facility with a prolonged steroid taper, ending 1 month prior to admission.In the ED, the patient had a chest x-ray that demonstrated bibasilar atelectasis and opacification, and a CT chest revealed right lower lobe consolidation and surrounding ground glass opacities. A respiratory pathogen PCR swab was negative. Sputum culture was negative for bacterial and fungal growth. Blood cultures did not grow any organisms. Given recent immunosuppression and imaging findings, a serum Cryptococcal antigen was drawn, which was positive with a titer of 1:128. A transthoracic needle biopsy of the patient's right lower lung was then performed. The specimen did not grow any bacteria or fungi and AFB stain on the tissue was negative. Pathology demonstrated a collection of histiocytes, neutrophils, and necrotic debris. PAS, GMS, and mucicarmine stains were positive for fungal organisms consistent with Cryptococcus species. Discussion: Cryptococcosis is a fungal infection due predominately to one of two encapsulated yeasts, Cryptococcus neoformans or Cryptococcus gattii. C. neoformans is found in soil worldwide, and infection typically begins with spore inhalation. Clinically significant disease is seen mostly in immunocompromised patients.Corticosteroids and interleukin inhibitors, such as anakinra (IL-1) and tocilizumab (IL-6), are used in the treatment of COVID-19. These medications have been associated with increased risk for opportunistic infections, including invasive fungal infections. The diagnosis of pulmonary cryptococcosis may be challenging, as symptoms are often nonspecific and may radiographically resemble bacterial pneumonia, malignancy, or other infections. Serum cryptococcal antigen detection tests may be helpful in establishing the diagnosis, as well as histopathology showing narrow-based budding yeast. Conclusion: Patients with prior COVID-19 infection commonly return to healthcare settings with sequelae of their previous coronavirus infection. In our case, it was the prior treatment of COVID-19, which included immunomodulating therapy, that lead to a secondary pulmonary cryptococcal infection. When evaluating pulmonary processes that evolve after an acute infection with COVID-19, it is important to keep a broad differential, including uncommon and/or opportunistic infectious etiologies, particularly when a patient has received prolonged courses of steroids and tocilizumab.
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TYPE: Late Breaking TOPIC: Chest Infections INTRODUCTION: Creutzfeld Jakob Disease (CJD) is a collective group of rare neurodegenerative diseases characterized by rapidly progressing cognitive decline, deficits in cortical function (aphasia, apraxia, agnosia), myoclonic jerks and extrapyramidal symptoms with a mortality of 100%. CASE PRESENTATION: We present a 72-year-old female who initially presented with aphasia, dyscalculia, right hemiparesis and dysgraphia.Upon arrival, she was hemodynamically stable and labs were remarkable for a positive COVID PCR test. CT head and CT angiogram was within normal limits. MRI was nonspecific. EEG showed left temporal lateralized periodic discharges (PLDs) at 1 Hz with a triphasic morphology and Lumbar puncture disclosed a protein of 79 mg/dL, glucose 65 mg/dL, WBC 1, HSV 1 and 2 PCR, cryptococcus, gram stain/culture AFB, and cytology were all negative. With concern for autoimmune encephalitis she was empirically started on IVIG without improvement. Paraneoplastic and autoimmune evaluation resulted pan negative. 14-3-3 CSF protein assay reported positive and diagnosis CJD was made. After goals of care discussion with the family, she was discharged home with hospice. DISCUSSION: Sporadic type (sCJD) accounts for about 85% of cases and occurs after somatic mutation in the gene for PrP protein. Rapid neurocognitive decline and cortical function deficits with negative infectious, autoimmune, and paraneoplastic workups should prompt further evaluation for CJD. CSF protein 14-3-3 has a sensitivity of 92%–96% for sCJD. EEG showing of a 1/second periodic triphasic sharp wave complex is present in 1/3 cases. CONCLUSIONS: Most recently, there have been some case reports indicating that the systemic immune response in COVID-19 could accelerate the clinical course of sCJD, however, a potential causal link remains unclear. DISCLOSURE: No significant relationships. KEYWORD: CJD
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A criptococose é uma doença fúngica e oportunista, causada pelo fungo da classe Blastomycetes, da família Cryptococcaceae e apresenta duas espécies patogênicas: C. neoformans e C. gattii. A infecção pode ser adquirida por quaisquer indivíduos saudáveis ou não, mas, as pessoas mais suscetíveis são os portadores de SIDA. A infecção no homem acontece por via respiratória;a levedura atinge os pulmões e, dependendo do estado imunológico do paciente, dissemina-se através por vias hematogênica ou linfática, para o sistema nervoso central, globo ocular e tecido cutâneo. O exame direto com coloração de tinta de nanquim é de fácil execução, rápido e barato permitindo a visualização das estruturas características do Cryptococcus spp, porém, o padrão-ouro para o diagnóstico é a associação do exame histopatológico com a cultura. Anfotericina B, é um medicamento fungicida que em associação a 5-flucitosina, constitui primeira opção de tratamento. Descrição do caso: Paciente feminina, 36 anos, venezuelana, com diagnostico de infecção pelo HIV há aproximadamente 2 anos, porém sem tratamento antirretroviral regular. Foi admitida em agosto de 2021 no Hospital de referência de Roraima por alteração neurológica (afasia, hemiparesia direita e alteração da marcha) com achados sugestivos de leucoencefalopatia multifocal progressiva (LEMP) na ressonância magnética do encéfalo;foi diagnosticada também com COVID-19. Durante a internação, evoluiu com surgimento de lesões elevadas, circunscritas, hipercrômicas em face, pescoço, tronco e membros superiores e lesão ulcerada de bordas elevadas de aproximadamente 5 cm na face medial do tornozelo esquerdo. Realizada biópsia das lesões que demonstraram infiltrado inflamatório linfohistiocitário, com esporos fúngicos de variados tamanhos, com cápsula espessa que se coram pela coloração HE e mais nitidamente pelo Grocott sugestivo de infecção por Cryptococcus neoformans. Análise de líquor realizado em 2 oportunidades teve exames diretos e culturas negativas para estruturas fúngicas;não foi possível realizar teste de aglutinação em Latex para Cryptococcus. Fez uso de Anfotericina B lipossomal e Fluconazol por 2 semanas, evoluindo com boa resposta cutânea, porém sem melhora do quadro neurológico. Comentário: A criptococose cutânea localizada uma condição na qual as lesões estão confinadas à pele, não disseminadas sistemicamente e ao mesmo tempo, não estão associadas a fungemia.