Disseminated Mucormycosis in a patient on long term immunosuppression: Severe fungal infections as multi-system disorders

Introduction: Mucormycosis is a rare, severe fungal infection with an incidence of 0.005 to 0.17 per million.1 but incidence has risen recently, particularly in the Asian subcontinent, due to use of immunosuppression for Covid19.2 Presentations can vary and are classified into: rhino-orbito-cerebral, pulmonary, cutaneous, disseminated, renal and gastrointestinal. Risk factors include diabetes, immunosuppression, iron overload, malnutrition, and prematurity.1,3 Although mucormycosis has an extremely high mortality rate and disseminated infection is usually fatal, treatment options exist if diagnosed early and surgical debridement may be curative. Objective(s): We present a case of mucormycois in a female patient in her 40s who was immunosuppressed with methotrexate for rheumatoid disease. This case is discussed to increase awareness of critical illness caused by opportunistic invasive fungal infections in immunosuppressed patients and promote timely identification and management. Method(s): We detail the clinical context and management of a patient with mucormycosis and discuss relevant literature. Result(s): A female patient in her 40s who had been experiencing upper respiratory tract symptoms for several weeks, including cough and brown sputum, was admitted with a presumptive diagnosis of methotrexate toxicity after a full blood count performed by the general practitioner demonstrated pancytopenia. Initially, National Early Warning System 2 score (NEWS2) was 2 but became intensely hypertensive during blood transfusion and then profoundly shocked with an escalating NEWS2. Broad-spectrum antibiotics and fluconazole were commenced for neutropenic sepsis and the patient was referred to critical care in multiple organ failure. Computerised tomography (CT) scan of the chest, abdomen and pelvis showed "left upper lobe consolidation, which with neutropenia might represent an angioinvasive aspergillosis". She had multiple areas of skin discolouration and desquamation. Haematology and Infectious Diseases opinions were sought, and a bone marrow biopsy was performed which showed severe toxic effects consistent with sepsis/life threatening infection. Progressive proptosis was noted, and CT scan of her head was requested. Sadly, she was never stable enough for CT transfer. Beta D Glucan and aspergillus antigen serology was negative. Broncho-alveolar lavage demonstrated Candida albicans and then, later, Rhizopus arrhizus was isolated and anti-fungal treatment changed to voriconazole and then amphotericin B. Upon reviewing the notes in light of the positive culture for Rhizopus, the patient had likely been exhibiting symptomatic Mucormycosis sinus infection for some time prior to this admission with disseminated infection. The patient's condition continued to deteriorate and she sadly died. Conclusion(s): * The Early Warning Score significantly underestimated how unwell the patient was upon arrival in ED, a systems-based assessment would have demonstrated that the patient had multiple system dysfunction and significant potential to deteriorate suddenly despite having stable observations * The methotrexate level has no clinical value in diagnosing or refuting a diagnosis of methotrexate toxicity * A full examination of the immunosuppressed patient including ENT is a necessity when searching for a source of infection * Invasive fungal infections can cause multi-system symptoms and atypical presentations * As a greater proportion of patients have received systemic immunosuppression for Covid-19, vigilance for more unusual pathogens, including Mucormycosis by clinicians is advised.

Pulmonary infections in cancer patients

Lymphangitis carcinomatosa refers to pulmonary interstitial involvement by cancer and is a dreaded clinical finding in oncology because it is a late manifestation indicative of metastatic malignancy, from either a lung or a nonlung primary cancer, and is associated with poor prognosis. Its presentation is nonspecific, often with subacute dyspnoea and a nonproductive cough in a person with a known history of malignancy, but in some cases is the first manifestation of cancer. CT imaging can be suggestive, typically demonstrating thickening of the peribronchovascular interstitium, interlobular septa and fissures. However, a biopsy may be required to confirm the pathological diagnosis as these changes can also be due to concurrent disease such as heart failure, ILD, infection, radiation pneumonitis and drug reactions. Diagnosis allows symptomatic treatment, with personalised treatment directed towards the primary cancer most likely to provide a meaningful benefit. Future research should focus on prospective clinical trials to identify new interventions to improve both diagnosis and treatment of lymphangitis carcinomatosa.Copyright © ERS 2021.

The Impact of The Neonatology Improving Projects on Neonatal Services In Bisha City During Covid 19 Pandemic

Introduction: It is thought of as a necessary service to provide high-quality care during pregnancy, labour, and the postpartum period. The fields of obstetrics/midwifery and neonatology, which are generally referred to as perinatology, have reduced maternal and newborn mortality and morbidity globally, but the COVID-19 pandemic brought on by the SARS-CoV-2-related COVID-19 virus posed a threat to the security of healthcare. Material(s) and Method(s): A prospective comparative study was conducted in a tertiary care hospital, Bisha city. I want to compare the outcome for 2 years (July 2020-June 2022) after shifting to the new unit with previous 2 years before shifting (July 2018-June 2020) in different aspect: The days on the mechanical ventilation, The IVH rate, The Mortality rate. In this study, I want to compare neonatal services outcomes (for preterm babies less than 37 weeks gestational age) after developing the infrastructure, manpower, Supplies and Policies after the shifting to the new department. Result(s): This is a prospective comparative study conducted in the department of neonatology, in a tertiary care hospital, Bisha city. Mean gestational age in before shifting to new unit, after shifting were 31, 33.34 respectively. Average weight were 1496, 1565 in before shifting to new unit, after shifting respectively. In our study, Average days on the mechanical ventilation were 14.78 days in before shifting to new unit group. Average days on the mechanical ventilation were 4.33 days in after shifting to new unit group. Conclusion(s): The provision of high quality and evidence-based perinatal care must remain a priority, even in the face of a pandemic. Restructuring in health care facility with New advance mechanical ventilators supporting Volume-targeted ventilation, 9 single rooms isolation for septic babies, T-piece resuscitator (in all OR suits, Delivery suits and ER), Total parental nutrition and also the all NICU policies updated especially for Caffeine citrate and fluconazole administration to preterm babies according to the AAP guidelines. Also all the department stuff completed the NRP and STABLE provider course as mandatory requirement to work in the NICU department. IVH rate, mortality rate was drastically reduced after shifting to the new unit than before shifting to new unit. Hence hospital restructuring in neonatology plays a crucial role to reduce mortality rate.Copyright © 2021 Muslim OT et al.

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.

COVID-19 in a patient with Good's syndrome and in 13 patients with common variable immunodeficiency

Antibody deficiencies constitute the majority of primary immunodeficiencies in adults. These patients have a well-established increased risk of bacterial infections but there is a lack of knowledge regarding the relative risks upon contracting COVID-19. In this monocentric study the disease course of COVID-19 in 1 patient with Good's syndrome and in 13 patients with common variable immunodeficiency (CVID) is described. The severity of disease ranged from very mild to severe. Several patients required hospitalization and immunomodulatory treatment but all survived. Although viral infections are not a typical feature of humoral immunodeficiencies we recommend that vigilance is increased in the management of patients with Good's syndrome and CVID during the COVID-19 pandemic.Copyright © 2021

Candida lipolytica Bloodstream Infection in an Adult Patient with COVID-19 and Alcohol Use Disorder: A Unique Case and a Systematic Review of the Literature.

Candida lipolytica is an uncommon Candida species causing invasive fungemia. This yeast is mainly associated with the colonisation of intravascular catheters, complicated intra-abdominal infections, and infections in the paediatric population. Here, we report a case of C. lipolytica bloodstream infection in a 53-year-old man. He was admitted for an alcohol withdrawal syndrome and mild COVID-19. Among the primary risk factors for candidemia, only the use of broad-spectrum antimicrobials was reported. The empiric treatment was commenced with caspofungin and then targeted with intravenous fluconazole. Infective endocarditis was ruled out using echocardiography, and PET/TC was negative for other deep-seated foci of fungal infection. The patient was discharged after blood culture clearance and clinical healing. To the best of our knowledge, this is the first case of C. lipolytica candidemia in a patient with COVID-19 and alcohol use disorder. We performed a systematic review of bloodstream infections caused by C. lipolytica. Clinicians should be aware of the possibility of C. lipolytica bloodstream infections in patients with alcohol use disorder, especially in a COVID-19 setting.

Hospital Clonal Outbreak of Fluconazole-Resistant Candida parapsilosis Harboring the Y132F ERG11p Substitution in a French Intensive Care Unit.

We report the first identification of a fluconazole-resistant Candida parapsilosis (FR-Cp) strain in our hospital, which subsequently caused an outbreak involving 17 patients (12 deaths) within a 26-bed French intensive care unit. Microsatellite genotyping confirmed that all FR-Cp isolates belonged to the same clone. Given recent reports of rapid dissemination of these emerging clones, routine testing of azole susceptibility for all Candida parapsilosis isolates should be encouraged, at least in ICU patients.

Nano-combination for Reviving the Activity of Fluconazole against Rhizopus delemar.

BACKGROUND: Rhizopus delemar, the main causative pathogen for the lethal mucormycosis and a severe threat during the COVID-19 pandemic, is resistant to most antifungals, including fluconazole, a known selective antifungal drug. On the other hand, antifungals are known to enhance fungal melanin synthesis. Rhizopus melanin plays an important role in fungal pathogenesis and in escaping the human defense mechanism, thus complicating the use of current antifungal drugs and fungal eradication. Because of drug resistance and the slow discovery of effective antifungals, sensitizing the activity of older ones seems a more promising strategy. METHODS: In this study, a strategy was employed to revive the use and enhance the effectiveness of fluconazole against R. delemar. UOSC-13, a compound synthesized in-house to target the Rhizopus melanin, was combined with fluconazole either as is or after encapsulation in poly (lactic-coglycolic acid) nanoparticles (PLG-NPs). Both combinations were tested for the growth of R. delemar, and the MIC50 values were calculated and compared. RESULTS: The activity of fluconazole was found to be enhanced several folds following the use of both combined treatment and nanoencapsulation. The combination of fluconazole with UOSC-13 caused a 5-fold reduction in the MIC50 value of fluconazole. Furthermore, encapsulating UOSC-13 in PLG-NPs enhanced the activity of fluconazole by an additional 10 folds while providing a wide safety profile. CONCLUSION: Consistent with previous reports, the encapsulation of fluconazole without sensitization showed no significant difference in activity. Collectively, sensitization of fluconazole represents a promising strategy to revive the use of outdated antifungal drugs back in the market.

Coronavirus disease 2019-associated mucormycosis - a syndemic

Coronavirus disease 2019 (COVID-19) and COVID-associated mucormycosis (CAM) came as a syndemic that not only severely increased morbidity and mortality but also posed a serious challenge for the healthcare system of a developing country like India. Although mucormycosis is a rare disease with a worldwide incidence of 0.43 cases per million population/year, these two COVID-19 waves caused a total of more than 14,000 cases in India itself. Mucormycosis is an angio-invasive fungal infection with rapid progression. The three major modalities of treatment involve early surgical debridement, initiation of antifungal therapy and controlling the predisposing risk factor. A complex interplay of factors, including pre-existing disease such as diabetes mellitus, use of immunosuppressants and immunomodulators, risk of hospital-acquired infection and immune dysregulation post-COVID-19, may all predispose to the development of CAM. Future research regarding the efficiency of newer antifungal with lower side effect profiles and evidence-based establishment of risk factors for adopting preventing strategies is the need of the hour. The disease is known to have high mortality despite the best treatment. We review in this article the aetiopathogenesis, various diagnostic modalities and treatment considerations for this disease.

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic.

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

COVID-19-associated candidiasis and the emerging concern of Candida auris infections.

The incidence of COVID-19-associated candidiasis (CAC) is increasing, resulting in a grave outcome among hospitalized patients with COVID-19. The most alarming condition is the increasing incidence of multi-drug resistant Candida auris infections among patients with COVID-19 worldwide. The therapeutic strategy towards CAC caused by common Candida species, such as Candida albicans, Candida tropicalis, and Candida glabrata, is similar to the pre-pandemic era. For non-critically ill patients or those with a low risk of azole resistance, fluconazole remains the drug of choice for candidemia. For critically ill patients, those with a history of recent azole exposure or with a high risk of fluconazole resistance, echinocandins are recommended as the first-line therapy. Several novel therapeutic agents alone or in combination with traditional antifungal agents for candidiasis are potential options in the future. However, for multidrug-resistant C. auris infection, only echinocandins are effective. Infection prevention and control policies, including strict isolation of the patients carrying C. auris and regular screening of non-affected patients, are suggested to prevent the spread of C. auris among patients with COVID-19. Whole-genome sequencing may be used to understand the epidemiology of healthcare-associated candidiasis and to better control and prevent these infections.

EXTENSIVE PNEUMATOCELES DUE TO PNEUMOCYSTIS JIROVECI PNEUMONIA IN A PATIENT NEWLY DIAGNOSED WITH HIV INFECTION

SESSION TITLE: Rare Pulmonary Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 01:35 pm - 02:35 pm INTRODUCTION: Pneumatoceles are air-filled cavitary lesions that are rarely seen in the lung after infection, trauma, or as part of a more diffuse cystic disease process. Several infectious agents have been associated with pneumatoceles, one of them being Pneumocystis Jirovecii, a potentially life-threatening fungus commonly seen as an opportunistic infection in immunocompromised patients. We present a case of bilateral extensive pneumatocele in a newly diagnosed HIV patient found to be positive for Pneumocystis pneumonia CASE PRESENTATION: A 52-year-old female presented to the emergency room for 2 months of shortness of breath, body aches, and chills. She was saturating at 86% on room air on arrival. Initial chest x-ray showed bilateral airspace disease. Had additional history of daily smoking, polysubstance abuse, and poor follow-up with doctors’ appointments due to social issues. She was started on oxygen support, steroids, antibiotics, and IV fluids. Labs were notable for normal overall WBC count but low lymphocyte count of 0.4. A CT Angiogram of the chest showed moderate to severe diffuse bilateral gas-filled cystic structures throughout the lungs, consistent with pneumatoceles. Infectious workup performed: COVID PCR, Influenza A/B antigen, legionella antigen, strep. pneumoniae antigen, B-D-glucan assay, histoplasma and blastomyces antigens, and HIV antibody. HIV antibody, strep pneumo antigen, and B-D-glucan assay came positive. She did not have a known diagnosis of HIV prior to this admission. Antibiotic regimen was changed to ceftriaxone, azithromycin, Bactrim, and fluconazole. Bronchoscopy with lavage was performed. Lavage samples were sent for cytology and found to be positive for Pneumocystis on GMS stain HIV viral load was checked and found to be at 1.4 million copies. CD4 count was less than 25 Patient was started on antiretroviral therapy in addition to prolonged course of Bactrim. She was ultimately discharged from the hospital in stable condition with pulmonary and infectious disease follow-up. At this time her pneumatoceles have improved on follow-up imaging. DISCUSSION: Pneumatoceles can rarely present as a complication of PCP pneumonia and can be a marker of more advanced disease. In our patient, pneumatoceles were identified first followed by diagnosis of HIV and PCP pneumonia. Overall incidence of post-infectious pneumatoceles is low at 2-8%. Prompt treatment and careful monitoring is needed due to risk of mortality from underlying infection and progression to pneumothorax. CONCLUSIONS: HIV with PCP infection complicated by pneumatocele formation is much less common due to improvements in HIV detection and screening for opportunistic infection, but should remain an important consideration in patients with unexplained cystic lung disease patterns, especially in patients without established outpatient follow-up or who don't see medical providers often. Reference #1: Thomas CF Jr, Limper AH: Pneumocystis pneumonia. N Engl J Med. 2004;350: pp. 2487-2498. Reference #2: Albitar, Hasan and Saleh, Omar M. Pneumocystis Pneumonia Complicated by Extensive Diffuse Pneumatoceles. Am J Med. 2019 May;132(5):e562-e563. Epub 2019 Jan 16. Reference #3: Ryu, Jay et al. Diffuse Cystic Lung Diseases. Frontiers of Medicine volume 7, pages 316–327 (2013) DISCLOSURES: No relevant relationships by Clifford Hecht

CRYPTIC CRYPTO: PULMONARY CRYPTOCOCCOSIS IN AN IMMUNOCOMPETENT HOST

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

COVID-19-INDUCED IMMUNOSUPPRESSION LEADING TO SECONDARY INFECTION AS DISSEMINATED COCCIDIOIDOMYCOSIS

SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Coccidioidomycosis caused by the fungi C. immitis and C. Posadasii is well known to be endemic to the Southwest United States. Less than 1% of these infections will manifest as extrapulmonary symptoms and multiple sites causing dissemination fungemia [1]. Risk factors for disseminated infection include exogenous immunosuppression, immunodeficiency, pregnancy, and ethnic backgrounds of African and Filipino descent [2]. CASE PRESENTATION: A 39-year-old previously immunocompetent Congolese male with recent onset of recurrent skin abscess, and positive testing for COVID-19 three week prior (not treated with steroids). He presents with shortness of breath, back pain, fevers after recently migrating from the Southwest region to the Midwest. Upon admission imaging with Computed Tomography (CT) revealed extensive pulmonary infiltrates (Fig 1), intra-abdominal abscesses, and magnetic resonance imaging revealing (MRI) osteomyelitis of the thoracic (Fig 2) and lumbar spine (Fig 3). His work of breathing continued to worsen, requiring prompt intubation, and he was initiated on a broad-spectrum antimicrobial regimen, including fluconazole, voriconazole, cefepime and vancomycin. Immunoglobulins, HIV and oxidative burst testing was unremarkable. Cultures from image-guided aspiration of the psoas abscess, incision, and drainages of skin abscess and bronchoalveolar lavage fluid were all positive for coccidioidomycosis, transitioned to amphotericin B. Course complicated with the development of multidrug-resistance pseudomonas aerogenes VAP treated with inhaled tobramycin and meropenem. He developed progressive acute respiratory distress syndrome with refractory hypoxemia. After 3 weeks of antimicrobial and anti-fungal treatment, a decision was made to transfer the patient to a lung transplant center, however, due to ongoing fungemia, he was deemed to be not a candidate for extracorporeal membrane exchange and lung transplantation. About a month into his hospitalization, the family decided to withdraw care. DISCUSSION: Reactivation of latent coccidiomycosis has been largely studied in the immunosuppressed population that includes HIV, hematological malignancies, and diabetes mellitus, however little is known about this fungal infection in the immunosuppressed state in the setting of COVID-19. Thus far only two case reports have been reported of co-infection if COVID-19 and pulmonary coccidioidomycosis [3]. The days of the COVID-19 pandemic might contribute to further delays in diagnosing this fungal infection due to similarities of pulmonary manifestation. CONCLUSIONS: This case demonstrates a COVID-19 infection leading to an immunosuppressed status resulting in disseminated infection from reactivation of latent coccidiomycosis. As a result, physicians must maintain a high level of suspicion for superimposed fungal infections in those with even relative immunosuppression from a recent COVID infection. Reference #1: Odio CD, Marciano BE, Galgiani JN, Holland SM. Risk Factors for Disseminated Coccidioidomycosis, United States. Emerg Infect Dis. 2017;23(2):308-311. doi:10.3201/eid2302.160505 Reference #2: Hector RF, Laniado-Laborin R. Coccidioidomycosis–a fungal disease of the Americas. PLoS Med. 2005;2(1):e2. doi:10.1371/journal.pmed.0020002 Reference #3: Shah AS, Heidari A, Civelli VF, et al. The Coincidence of 2 Epidemics, Coccidioidomycosis and SARS-CoV-2: A Case Report. Journal of Investigative Medicine High Impact Case Reports. January 2020. doi:10.1177/2324709620930540 DISCLOSURES: No relevant relationships by Stephen Doyle No relevant relationships by Connor McCalmon No relevant relationships by John Parent No relevant relationships by Jay Patel No relevant relationships by Angela Peraino No relevant relationships by Keval Ray

RISK AND PATTERN OF INFECTIONS IN NEWLY DIAGNOSED PATIENTS OF MULTIPLE MYELOMA VACCINATED UPFRONT AGAINST PNEUMOCOCCUS & INFLUENZA

Background: Infections contribute to an early mortality risk of 15 percent in newly diagnosed multiple myeloma(NDMM) cases. There is a limited literature on the type of infections in fully vaccinated NDMM patients. Aims: To study epidemiology, clinical profile and predictors of infection in NDMM who are immunised against pneumococci and influenza. Methods: NDMM patients were prospectively studied for 6 months for the pattern of infections . All patients were vaccinated with pneumococcal and Influenza vaccine at diagnosis. PJP prophylaxis and fluconazole prophylaxis was given for patients receiving high dose steroids while acyclovir was given to all. Infections were classified as microbiologically defined, clinically defined and fever of unknown focus according to definitions published by the International Immunocompromised Host Society. Severity of infections were graded according to the NCI CTCAE Ver5. Results: Forty-eight NDMM patients with a median age 55 years comprising of 26 males and 22 females were enrolled. Renal involvement was noted in 42% of enrolled patients and two third of them required renal replacement therapy. ISSIII and R-ISS III were 70.8 % and 62.5 % respectively. 85% had poor performance status(ECOG ≥2) at baseline. RVD was the most common regimen (37%)used. 6 patients received daratumumab based regimen. Treatment response of atleast VGPR was seen in 97 % of NDMM patients. A total of 19 episodes of infections were observed during 6 months. All episodes of infections were reported in the first 45 of myeloma diagnosis(Median 6 days;Range 0-45). Ten of these episodes of infection were diagnosed during the initial evaluation for myeloma defining events. Microbiological diagnosis was possible in 63 %. Commonest infectious agent was COVID 19(n=8) followed by Gram negative bacteria (n=5) viz E.coli and Klebsiella pneumoniae . None of the eight patients who developed COVID 19 infection had received COVID vaccine as they antedated the operationalisation of national guidelines for immunisation. Respiratory and the urinary tract were the most common focus of infection. All critically ill COVID patients succumbed to progressive respiratory failure and all patients with mild and moderate COVID illness recovered uneventfully. Early mortality in our cohort of forty eight patients was twenty percent(n=10). Three fourths of infections in our cohort were Grade≥3 severity. A total of seven deaths were attributable to infectious diseases in this cohort of NDMM patients. Imune paresis was seen in eighty four percent of patients at diagnosis. On follow up at 6 months;immune paresis had persisted in only thirty seven percent. Regression analysis of variables with odds of infection is shown in Table 1 Baseline BMI<18.5 kg/m2;albumin<3g/dl and ISS or R-ISS stage ≥ 2 was found to be have statistically significant odds of predicting infection risk in the cohort of patients. The choice of myeloma regimen, presence of high risk cytogenetics and response to therapy did not correlate with increased odds of infection in our cohort. Summary/Conclusion: Conclusion In this prospective study of NDMM patients vaccinated against pneumococci and influenza at baseline;infection attributable early mortality was 14.5 %. Advanced stage of presentation, hypoalbuminemia and baseline BMI < 18.5 kg/m2 correlated with increased odds of infection. COVID vaccination and COVID appropriate behavioural practices may mitigate COVID related outcomes including deaths in myeloma patients.

Determinants of fluconazole resistance and echinocandin tolerance in C. parapsilosis isolates causing a large clonal candidemia outbreak among COVID-19 patients in a Brazilian ICU.

Patients presenting with severe COVID-19 are predisposed to acquire secondary fungal infections such as COVID-19-associated candidemia (CAC), which are associated with poor clinical outcomes despite antifungal treatment. The extreme burden imposed on clinical facilities during the COVID-19 pandemic has provided a permissive environment for the emergence of clonal outbreaks of multiple Candida species, including C. auris and C. parapsilosis. Here we report the largest clonal CAC outbreak to date caused by fluconazole resistant (FLZR) and echinocandin tolerant (ECT) C. parapsilosis. Sixty C. parapsilosis strains were obtained from 57 patients at a tertiary care hospital in Brazil, 90% of them were FLZR and ECT. Although only 35.8% of FLZR isolates contained an ERG11 mutation, all of them contained the TAC1L518F mutation and significantly overexpressed CDR1. Introduction of TAC1L518F into a susceptible background increased the MIC of fluconazole and voriconazole 8-fold and resulted in significant basal overexpression of CDR1. Additionally, FLZR isolates exclusively harboured E1939G outside of Fks1 hotspot-2, which did not confer echinocandin resistance, but significantly increased ECT. Multilocus microsatellite typing showed that 51/60 (85%) of the FLZR isolates belonged to the same cluster, while the susceptible isolates each represented a distinct lineage. Finally, biofilm production in FLZR isolates was significantly lower than in susceptible counterparts Suggesting that it may not be an outbreak determinant. In summary, we show that TAC1L518F and FKS1E1393G confer FLZR and ECT, respectively, in CAC-associated C. parapsilosis. Our study underscores the importance of antifungal stewardship and effective infection control strategies to mitigate clonal C. parapsilosis outbreaks.

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.

Candida associated periodontitis in COVID- 19 era

Background: New Classification of Periodontal and Peri-implant Diseases and Conditions having worked into 2017 has defined candida-associated periodontal lesions as “Non-plaque-induced gingival diseases” associated with specific infection (list point 2.3). Patients with diagnosis Periodontal candidosis have been observed at the Division of Periodontology SPBGMU and City Periodontal Center “PAKS” more than for 25 years with an average quantity of 3-5 new cases a year. There had been formed a typical pattern for setting diagnosis and treatment. As a risk group was recognized, patients who predominantly had such general conditions as diabetes, immunosuppressive therapy, and heavy smokers. Since 2020 the pattern has been completely changed due to changing general conditions of the patients who consisted of the group and increasing quantity of periodontal candidosis about threefold. The core of the group has consisted of predominantly patients who recently had COVID-19 and/or underwent immunosuppressive therapy. Description of the procedure: Diagnostic procedure: Level 1. Anamnesis, clinical record, standard periodontal charting, estimation of periodontal and hygienical indices, absence or present mucosa lesions. CBCT Level 2. Clinical fluorescence diagnostic-wave length 400 ± 10 nm estimation gingival and mucosa condition. The cultural test for Candida detecting. Level 3. Cytology Treatment: in addition to SRP procedure there prescribed local and systemic antifungal therapy. 1. Photodynamic therapy (toluidine blue photosensitizer) 2. Local antifungal therapy - rinsing by Clotrimazole solution 3. Systemic antifungal therapy - Fluconazole 150 mg once in day 4. Modification of host response - Imudon 6 six in day 5. Toothpaste with the alkalic antifungal agent -sodium bicarbonate. Outcomes: Outcome control: Clinical investigation, the cultural test for Candida. Case: Female age 47 had a severe COVID-19 case, 3 months later she had rising level of activity periodontitis without response on usual periodontal therapy. Conclusions: Candida-associated periodontitis is difficult for diagnostic and treatment disease which use to occur quietly rare but nowadays have vastly increased.