Transplantation Infectious Diseases Research Articles

Antimicrobial stewardship in pediatric solid organ transplantation: Is it possible?

Solid organ transplant (SOT) recipients are at increased risk of severe outcomes associated with antimicrobial resistance (AMR). Antimicrobial stewardship programs (ASPs) play a vital role in mitigating the negative impacts of AMR. Pediatric evidence regarding ASP for SOT recipients is scarce, although many pediatric SOT centers have implemented different forms of ASP. This article summarized the available evidence relating to AMR among pediatric SOT recipients and discussed key strategies for the successful implementation of ASP among this population. The focus is primarily on antibacterial and secondarily on antifungal management. The development of multidisciplinary antimicrobial stewardship teams for pediatric SOT recipients is essential for successful stewardship implementation. Key stakeholders may include but are not limited to SOT recipients and their caregivers, primary SOT teams (transplant physicians, transplant pharmacists, transplant unit nurses, and transplant outpatient care team), transplant surgery teams, transplant infectious diseases teams, hospital AST, microbiology teams, infection prevention teams, quality improvement teams, and information technology teams. As the evidence for optimal ASP in pediatric SOT is still evolving, it is important to measure the impact of implemented interventions.

Antimicrobial stewardship in solid organ transplantation: Perspective from a Veterans Affairs Medical Center.

The importance of antimicrobial stewardship (AMS) activities specifically focused on solid organ transplant (SOT) recipients is increasingly recognized. In 2014, the Veterans Health Administration (VHA) created national guidance and committed resources to establish AMS programs at Veterans Affairs (VA) medical centers across the country. However, the AMS implementation is at the discretion of individual VA centers. We undertook an environmental scan of AMS activities in a tertiary care VA medical center. We describe AMS activities focused on SOT recipients. Strategies based on local epidemiology that leverage the electronic medical record together with engagement by transplant infectious diseases personnel are likely to be beneficial. AMS in SOT recipients is challenging yet impactful. Strategies described here may be useful for AMS activities focused on the SOT population.

420.6: Transplantation of Organs From SARS-CoV-2-Positive Donors To Uninfected (Non-lung) Solid Organ Transplant Recipients Has Not Resulted in Significant SARS-CoV-2 Related Morbidity Or Mortality

Introduction: The SARS-CoV-2 pandemic has conferred significant morbidity and mortality across the globe, especially for solid organ transplant (SOT) recipients. This has led to reluctance of using organs from SARS-CoV-2 infected donors due to concerns of disease transmission. However, this must be offset with an increase in wait list mortality. We sought to evaluate the use of organs from SARS-CoV-2 donors into (non-Lung) Solid Organ Transplant Recipients in a prospective fashion. Methods: We evaluated the use of organs from SARS-CoV-2 donors between 6/17/2021 to 2/24/2022. 18 patients were transplanted with SARS-CoV-2-positive donor (COVID+) organs: 3 heart, 4 liver, and 11 kidney recipients. SOT recipients were tested for presence of SARS-CoV-2 by RT-PCR prior to and after their operations. Induction immunosuppression was standard and not altered from protocol. Postoperatively, recipients were kept in modified droplet precautions and received post-exposure treatment recommended by Transplant Infectious Disease. Treatment regimens included remdesivir and monoclonal antibodies directed against SARS-CoV-2 (Figure 1). Perioperative and post discharge care was administered by a multidisciplinary care team with no significant alterations in care protocols. Results: SOT recipients of COVID+ organs at our institution have not experienced any significant morbidity or mortality from SARS-CoV-2. All patients are alive at current follow up with excellent allograft function with a median follow up for heart, liver, and kidney recipients of 235, 67, and 86 days respectively. All patients were vaccinated except for one liver patient who was status 1A due to fulminant acute liver failure. 13/18 patients had post-operative nasopharyngeal swabbing for RT-PCR based viral testing and two tested positive for SARS-CoV-2 at POD #8. Neither patient experience clinical symptoms of disease. Use of of SARS-CoV-2 did not appear to increase inpatient hospital stay. Median LOS for heart, liver, and kidney recipients was 40, 12.3, and 7.4 days respectively. Neither pre-transplant vaccination, use of COVID+ organs, nor post exposure prophylaxis resulted in increased risk of immunologic complications as only one recipient (heart) has experienced an acute cellular rejection episode to date Conclusion: Our experience indicates that COVID+ organs can be utilized successfully. The decision to use these organs was based on organ quality, individual patient need at the time the organ offer was made and whether a potential similar quality, COVID negative organ would be available to the patient in the near future. As evidenced by our data, successful use of COVID+ organs is dependent on multidisciplinary wait list and perioperative management to ensure appropriate donor:recipient selection and mitigation of transmission risk with use of post-exposure prophylaxis.

Editorial introductions.

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned to a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Genovefa A. PapanicolaouGenovefa A. PapanicolaouDr Genovefa A. Papanicolaou is the Director of Clinical Trials in the Infectious Disease Service at Memorial Sloan Kettering Cancer Center and Professor at Weill Cornell Medical College of Cornell University in New York, USA. Dr Papanicolaou is the current Chair of the Infectious Disease special Interest Group (ID-SIG) of the American Society for Transplantation and Cellular Therapy (ASTCT). Her research focuses on viral infections after stem cell transplantation and particularly cytomegalovirus (CMV). Her areas of interest are novel therapeutics, biomarkers and personalized infection management. Dionysios NeofytosDionysios NeofytosDionysios Neofytos is an Infectious Disease specialist with expertise in infectious disease complications in patients with hematologic malignancies and bone marrow and solid organ transplant recipients. Since the completion of his training in Infectious Diseases at Thomas Jefferson University Hospital in Philadelphia, PA, USA, in 2006 he has joined the Faculty and worked as an attending physician with the Transplant Infectious Disease Services at the Johns Hopkins University in Baltimore, MD, USA, and the Memorial Sloan Kettering Cancer Center in New York, NY, USA. Since 2016, he joined the Division f Infectious Diseases at the University Hospital of Geneva, in Geneva, Switzerland. His research and area of expertise are focusing on the epidemiology, diagnosis and management of viral and invasive fungal infections in immunocompromised hosts. Trish M. PerlTrish M. PerlTrish M. Perl, MD, MSc, is the H. Ben and Isabelle T. Decherd Chair in Internal Medicine (Infectious Diseases and Geographic Medicine) at UT Southwestern Medical Center in Dallas TX, USA. Dr Perl received her Medical Degree from the University of North Carolina (Chapel Hill), USA, and a Master of Science from McGill University in Montreal, Canada. She trained in Internal Medicine at the Royal Victoria Hospital and in Infectious Diseases and Clinical Epidemiology at the University of Iowa, USA. She rose through the ranks to Professor of Medicine at Johns Hopkins University School of Medicine, USA, and Epidemiology at the Bloomberg School of Public Health and is recognized globally for her innovation and research in healthcare associated infections, antimicrobial resistance, and their transmission and prevention. As the Hospital Epidemiologist at Johns Hopkins Hospital and Health System Epidemiologist, she developed extensive practical and research experience. Internationally, she has helped with outbreak management and mitigation including SARS, MERS CoV, Ebola and consults on guideline development and strategies to prevent emerging threats in healthcare. She is actively involved in monitoring the COVID-19 pandemic and supporting the national and local response.

Bring it on: Top five antimicrobial stewardship challenges in transplant infectious diseases and practical strategies to address them.

Antimicrobial therapies are essential tools for transplant recipients who are at high risk for infectious complications. However, judicious use of antimicrobials is critical to preventing the development of antimicrobial resistance. Treatment of multidrug-resistant organisms is challenging and potentially leads to therapies with higher toxicities, intravenous access, and intensive drug monitoring for interactions. Antimicrobial stewardship programs are crucial in the prevention of antimicrobial resistance, though balancing these strategies with the need for early and frequent antibiotic therapy in these immunocompromised patients can be challenging. In this review, we summarize 5 frequently encountered transplant infectious disease stewardship challenges, and we suggest strategies to improve practices for each clinical syndrome. These 5 challenging areas are: asymptomatic bacteriuria in kidney transplant recipients, febrile neutropenia in hematopoietic stem cell transplantation, antifungal prophylaxis in liver and lung transplantation, treatment of left-ventricular assist device infections, and Clostridioides difficile infection in solid-organ and hematopoietic stem-cell transplant recipients. Common themes contributing to these challenges include limited data specific to transplant patients, shortcomings in diagnostic testing, and uncertainties in pharmacotherapy.

1383. Universal Strongyloides Screening in a Heart Transplant Program in South Carolina: Just How Endemic Is It?

Abstract Background Strongyloides stercoralis is endemic in sub-Saharan Africa, Southeast Asia, Latin America, and the southeastern United States, particularly Appalachia, where Strongyloides seroprevalence approaches 2%. SC is considered a state in which Strongyloides is endemic, however the degree of endemnicity is not known. Here we define the epidemiology of chronic strongyloidiasis in our state, through data obtained via universal screening of heart transplant candidates at our center. Methods This single center retrospective study was performed at a 700 bed academic medical center that is the only comprehensive transplant center in SC. All adult patients who underwent heart transplant evaluation 1/1/2019 - 12/31/2020 were included. Routine pre-transplant evaluation by Transplant Infectious Diseases (TxID) was implemented in the heart transplant program in 2015 and universal screening with Strongyloides IgG began in late 2018. We assessed demographics, risk factors for exposure to Strongyloides, treatment, and outcomes for seropositive subjects. Results During the study period, 218 patients underwent heart transplant evaluation. Adherence to universal screening was 96.8% (211/218). 187 subjects (88.6%) had negative screening results (≤ 0.9 IV) and 24 subjects (11.4%) had equivocal or positive screening results (≥ 1.0 IV). Demographics and risk factors for the 24 equivocal/positive subjects are presented in Table 1. 15 equivocal/positive subjects (66.7%) received ivermectin and 9 (33.3%) did not. The majority of untreated patients were declined for transplant (8/9) and did not have a TxID evaluation (6/9). One untreated patient was waitlisted for transplant and has received ivermectin since being identified in this study. There were no episodes of hyperinfection or disseminated infection in the cohort. Table 1. Demographics and risk factors for subjects with equivocal or positive Strongyloides IgG Conclusion Universal screening of adult heart transplant candidates at SC’s only transplant center detected a Strongyloides seroprevalence rate of 11.4%. The majority of subjects with equivocal/positive Strongyloides IgG were born in the US and did not have other known risk factors (residence in the Appalachian region of SC, military service, overseas travel). These data suggest a high level of endemnicity of strongyloidiasis in SC. Disclosures All Authors: No reported disclosures

476. A Global Survey of Countermeasures Against the COVID-19 Pandemic Among Solid Organ Transplant Centers

BackgroundSolid organ transplantation (SOT) profoundly impacts vulnerable recipients with chronic end organ diseases. The COVID-19 pandemic disrupted healthcare systems, including organ transplants. We aimed to evaluate the responses of SOT centers to COVID-19 at the beginning of the pandemic around the world.MethodsWe conducted a web-based survey amongst transplant centers, sent to members of The American Society of Transplantation Infectious Diseases Community of Practice Group, between April and May 2020. The survey included basic information of each transplant center (number and types of transplants in 2019), the countermeasures employed against COVID-19 such as timing of postponing of transplantation, and management of outpatient clinics including implementation of telemedicine and screening for in-person visits.ResultsA total of 65 centers from 19 countries responded (Table 1). Regarding the percentage of hospitalized patients with COVID-19 at the time of the survey, 39 (60%) centers reported < 10%, two centers reported > 80%. All centers reduced their services to some extent as shown in Table 2. Centers reported postponing living donor kidney transplant (50/58, 86%), deceased donor kidney transplant (20/57, 35%), living donor liver transplant (32/42, 80%), deceased donor liver transplant (17/41, 41%), lung transplant (20/31, 65%), heart transplant for LVAD (18/33, 55%) and non-LVAD patients (18/33, 55%). In March and April 2020, cancellation of pre- and post- transplant clinics were reported by 36/64 (56%) and 17/65 (26%) centers. Postponing clinic appointments were reported by 56/65 (86%) centers. Most institutions (54/64, 85%) used telemedicine. Screening for COVID-19 for clinic visits was done by telephone, in-person questionnaires and/or temperature checks. ConclusionDuring the early phase of the pandemic, when management strategies were highly uncertain, non-urgent and living donor transplants were frequently postponed. Emergent liver transplants continued regardless. These findings could help us navigate SOT in future epidemics. Limitations included a small sample and lack of assessment of clinical outcomes from postponing SOT. Disclosures Deepali Kumar, MD, MSc, FRCPC, Astellas (Individual(s) Involved: Self): Speakers’ bureau; Atara Biotherapeutics (Individual(s) Involved: Self): Grant/Research Support; GSK (Individual(s) Involved: Self): Consultant, Grant/Research Support; Merck (Individual(s) Involved: Both Myself and my Spouse/Partner): Advisor or Review Panel member, Grant/Research Support; Oxford immunotec (Individual(s) Involved: Self): Consultant, Grant/Research Support; Pfizer (Individual(s) Involved: Self): Speakers’ bureau; Roche (Individual(s) Involved: Self): Consultant, Grant/Research Support; Sanofi (Individual(s) Involved: Self): Advisor or Review Panel member; Shire/Takeda (Individual(s) Involved: Both Myself and my Spouse/Partner): Advisor or Review Panel member, Grant/Research Support Lara Danziger-Isakov, MD, MPH, Ansun (Individual(s) Involved: Self): Scientific Research Study Investigator; Astellas (Individual(s) Involved: Self): Scientific Research Study Investigator; Merck (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Pfizer (Individual(s) Involved: Self): Scientific Research Study Investigator; Shire (Individual(s) Involved: Self): Consultant, Scientific Research Study Investigator; Viracor: Grant/Research Support

Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Poor outcome of patients with COVID-19 after CAR T-cell therapy for B-cell malignancies: results of a multicenter study on behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Poor Outcome of Patients with COVID-19 after CAR T-Cell Therapy for B-Cell Malignancies: Results from a Multicenter Study on Behalf of the European Society for Blood and Marrow Transplantation (EBMT) Infectious Diseases Working Party and the European Hematology Association (EHA) Lymphoma Group

Return to School and COVID-19 Vaccination for Pediatric Solid Organ Transplant Recipients in the United States: Expert Opinion for 2021-2022.

The COVID-19 pandemic continues to generate challenges for pediatric solid organ transplant (SOT) recipients and their families. As rates of COVID-19 fluctuate, new SARS-CoV-2 variants emerge, and adherence to and implementation of mitigation strategies vary from community to community, questions remain about the best and safest practices to prevent COVID-19 in vulnerable patients. Notably, decisions about returning to school remain difficult. We assembled a team of specialists in pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control to re-address concerns about school re-entry, as well as COVID-19 vaccines, for pediatric SOT recipients in the United States in 2021. Based on available literature and guidance from national organizations, we generated expert statements specific to pediatric SOT recipients focused on school attendance in 2021.

DEXAMETHASONE AND AMPHOTERICIN B TO THE RESCUE: A CASE OF HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS

TOPIC: Critical Care TYPE: Fellow Case Reports INTRODUCTION: Hemophagocytic lymphohistiocytosis (HLH) is a rare disease characterized by immune system overstimulation resulting in widespread inflammation, a cytokine surge, and multisystem organ failure. HLH is associated with significant mortality, so early recognition and a multidisciplinary approach to treatment are key for improved survival. CASE PRESENTATION: A 59-year-old kidney and pancreas transplant recipient presented with diarrhea, fevers, altered mental status, and acute kidney injury. He was transferred to the ICU due to respiratory distress and was started on antibiotics. CT scan of the chest and abdomen showed a small right lower lobe consolidation and mild splenomegaly. Sputum, urine, and blood cultures were negative. Serum fungitell was elevated and Aspergillus galactomannan serum antigen was positive. Serum Histoplasma antigen was >25ng/mL and urine Histoplasma antigen was 7.8ng/mL. Amphotericin B was started and hematology was consulted for presumed HLH secondary to histoplasmosis with elevated ferritin (7559 ng/mL) and triglycerides (227). Bone marrow aspirate demonstrated foamy histocytes and hemophagocytic histiocytes as well dimorphic fungal forms in the interstitium and within a granuloma on GMS stain consistent with Histoplasma. Dexamethasone was initiated at 10mg/m2. Soluble IL-2R was 14,120 U/mL. He clinically improved on dexamethasone and was transitioned from amphotericin to itraconazole. DISCUSSION: At least 5 out of 8 of the following criteria must be met for a diagnosis of HLH: fever, splenomegaly, cytopenia, hypertriglyceridemia and/or hypofibrinogenemia, hemophagocytosis in bone marrow, spleen or lymph nodes, low/absent NK-cell activity, ferritin ≥ 500 mg/L, and soluble CD25 ≥2400 U/mL. This patient had 6/8 of the diagnostic criteria for HLH: fever, splenomegaly, hypertriglyceridemia, ferritin >500, high soluble IL-2 receptor, and hemophagocytosis in bone marrow. A multidisciplinary discussion involving critical care, hematology, and transplant infectious disease was held about initiating Etoposide due to rising ferritin (based on evidence supporting the use of Etoposide in pediatric patients with HLH), however, data is lacking regarding how to treat adult patients with HLH and histoplasmosis. He was clinically improving without Etoposide and there was concern that Etoposide would make his histoplasmosis more difficult to treat, so he was not given Etoposide. Histoplasma is a known but rare cause of HLH (<50 published cases). Due to the rarity of HLH and its risk for mortality, it is important to have a high index of suspicion to test for HLH in an immunosuppressed patient who presents with fevers. CONCLUSIONS: Working with a multidisciplinary team was essential to both the diagnosis and management of HLH due Histoplasma due to a lack of evidence about optimal treatment. Research is needed to improve outcomes for patients with HLH due to Histoplasma. REFERENCE #1: Hayden, A., Park, S., Giustini, D., Lee, A. Y., & Chen, L. Y. (2016). Hemophagocytic syndromes (HPSs) including hemophagocytic lymphohistiocytosis (HLH) in adults: A systematic scoping review. Blood reviews, 30(6), 411–420. https://doi.org/10.1016/j.blre.2016.05.001 REFERENCE #2: Bergsten, E., Horne, A., Aricó, M., Astigarraga, I., Egeler, R. M., Filipovich, A. H., Ishii, E., Janka, G., Ladisch, S., Lehmberg, K., McClain, K. L., Minkov, M., Montgomery, S., Nanduri, V., Rosso, D., & Henter, J. I. (2017). Confirmed efficacy of etoposide and dexamethasone in HLH treatment: long-term results of the cooperative HLH-2004 study. Blood, 130(25), 2728–2738. https://doi.org/10.1182/blood-2017-06-788349 REFERENCE #3: Filipovich A. H. (2009). Hemophagocytic lymphohistiocytosis (HLH) and related disorders. Hematology. American Society of Hematology. Education Program, 127–131. https://doi.org/10.1182/asheducation-2009.1.127 DISCLOSURES: No relevant relationships by Maureen McElligott, source=Web Response No relevant relationships by Meilinh Thi, source=Web Response

CAUGHT BY CONFUSA: A RARE CASE OF WEISELLA CONFUSA IN A LIVER TRANSPLANT PATIENT

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: Weisella confusa is a gram-positive bacteria typically found in gut flora. It is a rare cause of bacteremia in immunocompromised patients, especially those with malignancy. When grown in blood culture isolates, it serves as a harbinger of polymicrobial infection. It is inherently vancomycin resistant and treatment is based on susceptibility panel. In this case, we demonstrate W. confusa bacteremia in the setting of broad-spectrum antibiotic prophylaxis but no immunosuppressive therapy. CASE PRESENTATION: A 57-year-old woman with ulcerative colitis and autoimmune hepatitis and primary sclerosing cholangitis (PSC) overlap requiring liver transplant complicated by recurrent PSC was admitted for odynophagia due to a tongue lesion. She developed progressive synthetic liver dysfunction resulting in altered mental status, oliguric renal failure, and Klebsiella bacteremia with concurrent C. difficile colitis. Triple immunosuppressive therapy was halted and linezolid, aztreonam and oral vancomycin were initiated. Though she completed an antibiotic course with rapid clearance of bacteremia, prophylactic meropenem, micafungin, and oral vancomycin were administered and weekly surveillance cultures were drawn in anticipation of repeat transplant.One month later, four of four blood cultures grew W. confusa, followed by Lactobacillus rhamnosus, Enterococcus faecalis, and Candida krusei soon thereafter. Antimicrobials were escalated to amphotericin B, daptomycin, aztreonam, linezolid, and metronidazole, though she developed shock requiring multiple vasopressors. Computed tomography was obtained for source identification and demonstrated a right upper lobe pulmonary abscess and multiple hepatic abscesses. Upon discussions with the patient's family, care was withdrawn and she died soon after. DISCUSSION: W. confusa is a rare isolate from blood cultures and is generally associated with polymicrobial infections. Previous studies have shown that the majority of cases occur in the setting of malignancy, though there has been one other documented case in a liver transplant patient. In addition, a study conducted in pediatric liver transplant patients demonstrated Weisella isolates in stool samples, reflecting increased gut colonization with this organism. It is a naturally vancomycin resistant organism and misidentification as Lactobacillus by traditional speciation methods often results in inappropriate therapy. Here we demonstrate a case of Weisella bacteremia likely secondary to gut translocation. Given its natural vancomycin resistance, it is likely that prophylactic oral vancomycin for C. difficile resulted in W. confusa overgrowth and facilitated her decompensation via pre-existing defects to the gut mucosal barrier from ulcerative colitis. CONCLUSIONS: W. confusa should be considered an opportunistic bacteria warranting infectious disease specialist consultation to assist in management. REFERENCE #1: 1. Kamboj, K., Vasquez, A., & Balada-Llasat, J. M. (2015). Identification and significance of Weissella species infections. Frontiers in microbiology, 6, 1204. https://doi.org/10.3389/fmicb.2015.012042. Kumar, A., Augustine, D., Sudhindran, S., et. al. (2011). Weisella confusa: a rare cause of vancomycin-resistant Gram-positive bacteremia. Journal of Medical Microbiology, 60(10), 1538-41.3. Spiegelhauer, M. R., Yusibova, M., Rasmussen, I., Fuglsang, K. A., Thomsen, K., & Andersen, L. P. (2020). A case report of polymicrobial bacteremia with Weissella confusa and comparison of previous treatment for successful recovery with a review of the literature. Access microbiology, 2(5), acmi000119. https://doi.org/10.1099/acmi.0.0001194. Green, M., Barbadora, K., & Michaels, M. (1991). Recovery of vancomycin-resistant gram-positive cocci from pediatric liver transplant recipients. Journal of clinical microbiology, 29(11), 2503–2506. https://doi.org/10.1128/JCM.29.11.2503-2506.19915. Salimnia, H., Alangaden, G. J., Bharadwaj, R., Painter, T. M., Chandrasekar, P. H., & Fairfax, M. R. (2011). Weissella confusa: an unexpected cause of vancomycin-resistant gram-positive bacteremia in immunocompromised hosts. Transplant infectious disease : an official journal of the Transplantation Society, 13(3), 294–298. https://doi.org/10.1111/j.1399-3062.2010.00586.x6. Fairfax, M. R., Lephart, P. R., & Salimnia, H. (2014). Weissella confusa: problems with identification of an opportunistic pathogen that has been found in fermented foods and proposed as a probiotic. Frontiers in microbiology, 5, 254. https://doi.org/10.3389/fmicb.2014.00254 DISCLOSURES: No relevant relationships by Samuel Chung, source=Web Response No relevant relationships by Ashwin Kelkar, source=Web Response No relevant relationships by Joseph Mailman, source=Web Response

DISSEMINATED BLASTOMYCOSIS PRESENTING AS MONOARTICULAR SEPTIC ARTHRITIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Blastomycosis is a dimorphic fungus that causes acute or chronic pneumonia with extrapulmonary involvement in a minority of cases. Rarely it is implicated in disseminated disease causing joint involvement leading to septic arthritis. Recognizing blastomycosis as an important cause of septic arthritis and starting treatment is necessary to prevent joint destruction and overwhelming disseminated infection. CASE PRESENTATION: A 29-year-old male with no significant past medical history presented to the hospital with chief complaint of right knee pain of 3 weeks' duration associated with recent onset of productive cough, dyspnea on exertion and chest pain. Admitting vitals were remarkable for tachycardia and fever of 101 F. Physical examination revealed right knee swelling and pain on active and passive range of motion without overlying erythema. Joint aspiration revealed 68,000 WBC with 88% neutrophils with negative crystals. Cultures from synovial fluid grew blastomyces dermatitidis. During the hospital stay, patient's respiratory status worsened, and he was transferred to the ICU and intubated. CT Chest showed diffuse bilateral pulmonary nodules, suspicious for atypical pneumonia versus acute respiratory distress syndrome. Bronchoscopy was done and specimens were sent for culture. He was initially started and then maintained on broad spectrum antibiotics. Once respiratory and synovial cultures grew blastomyces, patient was started on IV amphoterecin. Patient's condition improved dramatically after starting amphoterecin. His remaining ICU course involved extubation, tracheostomy and gradual weaning of pressors. His knee pain and swelling subsided after starting amphoterecin and patient was discharged to rehab in stable condition on itraconazole. DISCUSSION: This case highlights the rare presentation of disseminated blastomycosis as monoarticular septic arthritis. About 3% of patients with blastomycosis have joint involvement. Extrapulmonary blastomycosis is usually seen in association with pneumonia which can often be severe enough to cause ARDS and shock, like our patient. It is important to have a high index of suspicion for blastomycosis in patients presenting with septic arthritis with an active pulmonary process and B symptoms. Diagnosis of blastomycosis is with culture, urinary and serum antigens. Treatment involves amphoterecin B followed by itraconazole for patients with severe disseminated disease. CONCLUSIONS: Disseminated blastomycosis can present with symptoms of extrapulmonary spread of disease. Diagnosis is with antigen identification in serum and urine and by culture. Treatment involves amphoterecin B and itraconazole. REFERENCE #1: Chapman, Stanley W., Andrew C. Lin, Katherine A. Hendricks, Rathel L. Nolan, Mary M. Currier, Ken R. Morris, and Helen R. Turner. "Endemic blastomycosis in Mississippi: epidemiological and clinical studies." In Seminars in respiratory infections, vol. 12, no. 3, pp. 219-228. 1997. REFERENCE #2: Wheat, L. J. "Antigen detection, serology, and molecular diagnosis of invasive mycoses in the immunocompromised host." Transplant infectious disease 8, no. 3 (2006): 128-139. DISCLOSURES: No relevant relationships by Fatima Ayub, source=Web Response No relevant relationships by Muhammad Hasib Khalil, source=Web Response

Pneumocystis jirovecii: The Changing Landscape for Prophylaxis.

Pneumocystis jirovecii: The Changing Landscape for Prophylaxis.

A Comprehensive Evaluation of Risk Factors for Pneumocystis jirovecii Pneumonia in Adult Solid Organ Transplant Recipients: A Systematic Review and Meta-analysis.

There is no consensus guidance on when to reinitiate Pneumocystis jirovecii pneumonia (PJP) prophylaxis in solid organ transplant (SOT) recipients at increased risk. The 2019 American Society of Transplantation Infectious Diseases Community of Practice (AST IDCOP) guidelines suggested to continue or reinstitute PJP prophylaxis in those receiving intensified immunosuppression for graft rejection, cytomegalovirus (CMV) infection, higher dose of corticosteroids, or prolonged neutropenia. A literature search was conducted evaluating all literature from existence through April 22, 2020, using MEDLINE and EMBASE. (The International Prospective Register of Systematic Reviews registration number: CRD42019134204). A total of 30 studies with 413 276 SOT recipients were included. The following factors were associated with PJP development: acute rejection (pooled odds ratio [pOR], 2.35; 95% confidence interval [CI], 1.69-3.26); study heterogeneity index [I2] = 23.4%), CMV-related illnesses (pOR, 3.14; 95% CI, 2.30-4.29; I2 = 48%), absolute lymphocyte count <500 cells/mm3 (pOR, 6.29; 95% CI, 3.56-11.13; I2 = 0%), BK polyomavirus-related diseases (pOR, 2.59; 95% CI, 1.22-5.49; I2 = 0%), HLA mismatch ≥3 (pOR, 1.83; 95% CI, 1.06-3.17; I2 = 0%), rituximab use (pOR, 3.03; 95% CI, 1.82-5.04; I2 = 0%), and polyclonal antibodies use for rejection (pOR, 3.92; 95% CI, 1.87-8.19; I2 = 0%). On the other hand, sex, CMV mismatch, interleukin-2 inhibitors, corticosteroids for rejection, and plasmapheresis were not associated with developing PJP. PJP prophylaxis should be considered in SOT recipients with lymphopenia, BK polyomavirus-related infections, and rituximab exposure in addition to the previously mentioned risk factors in the American Society of Transplantation Infectious Diseases Community of Practice guidelines.

Editorial introductions.

Current Opinion in Organ Transplantation was launched in 1996. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of organ transplantation is divided into 18 sections that are reviewed once a year. Each section is assigned a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Josep M. GrinyóJosep M. GrinyóDr Josep M. Grinyó, MD, PhD, is Emeritus Professor of Medicine at the University of Barcelona. Dr Grinyó's research work on renal transplantation has been focused on immunosuppression, ischemia-reperfusion injury and chronic allograft damage in the clinical setting and in experimental animal models. He has hold more than 60 competitive research projects and he has authored more than 340 articles and given more than 250 invited lectures. He has acted as associate editor and reviewer in the top ranked journals in his field of expertise (AJT, CJASN, JASN, NEJM, NDT, TI, Lancet). He has been member of the councils of the scientific societies and chair of several scientific programs committees of congresses of these societies (TTS, ERA-EDTA, ESOT, ISN). He is member of several steering committees and DSMBs of international research consortiums on cell therapy, biomarker-driven immunosuppression, treatment of autoimmune nephritis and organ preservation. He is reviewer of competitive research applications for research organisations in Spain, Belgium, Germany, France (Inserm), Argentine, Austria, USA and UK (MRC, EME Experts). Meenakshi M. RanaMeenakshi M. RanaDr Meenakshi M. Rana received her medical degree from Brown University, followed by internal medicine training at University of Michigan and infectious disease fellowship at Mount Sinai in New York City. She is now Associate Professor of Medicine and Director of Transplant Infectious Disease at Icahn School of Medicine at Mount Sinai.

Editorial introductions.

Current Opinion in Infectious Diseases was launched in 1988. It is part of a successful series of review journals whose unique format is designed to provide a systematic and critical assessment of the literature as presented in the many primary journals. The field of infectious diseases is divided into 11 sections that are reviewed once a year. Each section is assigned to a Section Editor, a leading authority in the area, who identifies the most important topics at that time. Here we are pleased to introduce the Section Editors for this issue. SECTION EDITORS Genovefa A. PapanicolaouGenovefa A. PapanicolaouGenovefa A. Papanicolaou is an Infectious Disease physician focusing in patients with hematologic malignancies and hematopoietic cell transplant recipients. She is the Director of Clinical Trials for the Department of Subspecialty Medicine at Memorial Sloan Kettering Cancer Center and Professor at Weill Cornell Medical College at Cornell University in New York, USA. Her research interests include viral infections, biomarkers and precision prevention. She serves in a volunteer capacity as Chair of the Infectious disease special interest group (ID-SIG) of the American Society of Transplantation and Cellular Therapy (ASTCT). Dionysios NeofytosDionysios NeofytosDionysios Neofytos is an Infectious Disease specialist with expertise in infectious disease complications in patients with hematologic malignancies and bone marrow and solid organ transplant recipients. Since the completion of his training in Infectious Diseases at Thomas Jefferson University Hospital in Philadelphia, PA, USA, in 2006 he has joined the Faculty and worked as an attending physician with the Transplant Infectious Disease Services at the Johns Hopkins University in Baltimore, MD, USA, and the Memorial Sloan Kettering Cancer Center in New York, NY, USA. Since 2016, he joined the Division of Infectious Diseases at the University Hospital of Geneva, in Geneva, Switzerland. His research and area of expertise are focusing on the epidemiology, diagnosis and management of viral and invasive fungal infections in immunocompromised hosts. Trish M. PerlTrish M. PerlTrish M. Perl, MD, MSc, is the Jay P Sanford Professor in the Departments of Medicine (Infectious Diseases) and the Chief of the Division of Infectious Diseases at UT Southwestern Medical Center in Dallas TX, USA. She formerly was at Johns Hopkins University School of Medicine, USA, in the Division of Infectious Diseases in the Department of Medicine, in Epidemiology at the Bloomberg School of Public Health and the Senior Epidemiologist for Johns Hopkins Health System. Dr Perl received her Bachelor of Arts and medical degree from the University of North Carolina at Chapel Hill, USA, and a Master of Science degree from McGill University in Montreal, Canada. She completed a residency in internal medicine at McGill University and a fellowship in infectious diseases and clinical epidemiology at the University of Iowa, USA. She was on faculty at the University of Iowa for several years before moving to Hopkins where she was the Hospital Epidemiologist at Johns Hopkins Hospital from 1996 to 2011 and then the Health System Epidemiologist until 2016 when she moved to UTSW. She has extensive practical and research experience in the field of healthcare associated infections and resistant and epidemiologically significant organisms and is recognized globally for her innovation and research in healthcare associated infections, antimicrobial resistance, their transmission and prevention. Because of this she helped manage international outbreaks including SARS, MERS CoV, Ebola and consults with international governments on guideline development and strategies to prevent healthcare associated and respiratory virus infections and antimicrobial resistance. An active researcher, Dr Perl has been funded by the CDC, BARDA and the Veteran's Affairs Administration over the years. She has authored or coauthored over 250 peer-reviewed articles. She actively reviews grants for the NIH.

P-18: COVID-19 in Small Bowel Transplant Recipients: A Single Center Experience

Introduction: Coronavirus disease 2019 (COVID-19) outbreak posed unique challenges for immunosuppressed patients. Little is known about the clinical course and immunosuppression management of this novel infection in intestinal transplant recipients. Methods: We experienced 6 adult intestinal transplant recipients who had a positive swab test of COVID-19 and symptoms. Baseline characteristics, clinical presentation, management of immunosuppressive therapy and outcomes were collected. Results: Median age was 53 years (range 30-71). They had 3 liver-free composite allografts, 2 isolated intestine, and 1 intestine-kidney with median time from transplant of 8 years (range 4-12). Maintenance immunosuppressive therapy was tacrolimus/steroid in 4, and tacrolimus monotherapy in 2 patients. The most common symptom was cough (n=5) followed by fever (n=3) and dyspnea (n=3). All had ground glass opacities on computed tomography. Four patients were admitted to our institution but two were managed at local hospital due to difficulty of transportation. Immunosuppression therapy was never suspended and was reduced for one patient. Pharmacological therapy consisted in remdesivir and steroids for 4 recipients (67%) associated with convalescent plasma in 2 cases (33%) plus tocilizumab in 1 case (17%), and steroids for 2 patients (33%) associated with convalescent plasma in 1 case (17%). Two patients required intubation for acute respiratory distress syndrome. One patient received antibiotics for superimposed bacterial pneumonia. Mean white blood cells and lymphocyte count were 4.72±0.6 k/uL and 0.96±0.65 k/uL at presentation, respectively. Mean D-Dimer, C-reactive protein and ferritin were 740±160 ng/ml, 4.1±5 mg/dl and 249±149 ng/ml, respectively at presentation, with a peak of 1255±785 mg/ml, 10.9±8 mg/dl and 630±318 ng/ml, respectively. No significant changes were noted in liver and renal function. Before discharge, all patients underwent ileoscopy and allograft biopsies with no evidence of inflammation/rejection. Mean hospital stay was 36±21 days. Death occurred in 2 patients (33%) who were managed at local hospital. No recurrence was noted with mean follow up of 90 days. Conclusions: We treated intestinal transplant recipients symptomatic for COVID-19 without immunosuppression interruption. No increased inflammation or rejection was noted in the intestinal grafts. Aggressive treatment of COVID-19 infection should be granted under expertise of intestinal transplant and transplant infectious disease team.

A eulogy for Dr Francisco Miguel Marty Forero

As some of those who were lucky enough to have been mentored by Dr Francisco Marty in transplant infectious diseases, we stand with the larger medical community in mourning his untimely death and in commemorating him as a uniquely exceptional and talented physician, investigator, teacher, mentor, friend, artist, and human being.

Prevalence and predictors of SARS-CoV-2 antibodies among solid organ transplant recipients with confirmed infection.

It remains uncertain whether immunocompromised patients including solid organ transplant (SOT) recipients will have a robust antibody response to SARS‐CoV‐2 infection. We enrolled all adult SOT recipients at our center with confirmed SARS‐CoV‐2 infection who underwent antibody testing with a single commercially available anti‐nucleocapsid antibody test at least 7 days after diagnosis in a retrospective cohort. Seventy SOT recipients were studied (56% kidney, 19% lung, 14% liver ± kidney, and 11% heart ± kidney recipients). Thirty‐six (51%) had positive anti‐nucleocapsid antibody testing, and 34 (49%) were negative. Recipients of a kidney allograft were less likely to have positive antibody testing compared to those who did not receive a kidney (p = .04). In the final multivariable model, the years from transplant to diagnosis (OR 1.26, p = .002) and baseline immunosuppression with more than two agents (OR 0.26, p = .03) were significantly associated with the antibody test result, controlling for kidney transplantation. In conclusion, among SOT recipients with confirmed infection, only 51% of patients had detectable anti‐nucleocapsid antibodies, and transplant‐related variables including the level and nature of immunosuppression were important predictors. These findings raise the concern that SOT recipients with COVID‐19 may be less likely to form SARS‐CoV‐2 antibodies.