Vikram, Holenarasipur R.

Abstract Background More accounts of opportunistic infection in COVID-19 patients are emerging. At our institution, we identified 2 COVID-19 patients with Pneumocystis jiroveci pneumonia (PJP) opportunistic infection. This prompted a review of the literature to identify trends in patient characteristics, risk factors, and outcomes in this population. Methods A literature review was conducted using PubMed that identified 13 other patients with both COVID-19 and PJP infection. Age, gender, human immunodeficiency virus (HIV) status, other immunocompromised states, time between COVID-19 and PJP diagnosis, and clinical outcomes were captured for analysis. Results Eleven patients were male. The average age was 56 years. All but 2 patients were immunocompromised. At time of PJP diagnosis, seven patients had newly diagnosed HIV and one had known, well-controlled HIV. One patient had rheumatoid arthritis receiving leflunomide, 1 had ulcerative colitis receiving budesonide and sulfasalazine, 2 patients had multiple myeloma whereby both were on lenalidomide, 1 patient was a renal transplant recipient immunosuppressed on tacrolimus, mycophenolate, and methylprednisolone, and 1 patient had chronic lymphocytic leukemia getting fludarabine, cyclophosphamide, and rituximab. Nine patients had positive COVID-19 and PJP tests performed within 7 days of one another. One patient tested positive for PJP 54 days into admission for COVID-19. This patient received high dose steroids and tocilizumab for initial COVID-19 infection. Three patients were re-hospitalized with PJP after a recent admission for COVID-19 pneumonia, with a mean time to readmission of 25 days. One of these 3 patients had no treatment for COVID-19, while 2 received steroids. Five of the total 15 patients (33%) died. Conclusion COVID-19 treatments with high dose steroids and tocilizumab can make patients vulnerable for opportunistic infection with PJP. Furthermore, COVID-19 is known to cause lymphopenia which may further increase this risk. A diagnosis of concomitant PJP can be especially challenging due to nearly identical radiographical findings. Serum beta-D glucan and HIV testing can be especially helpful in this situation, and there should be a low threshold for performing bronchoalveolar lavage. Disclosures All Authors: No reported disclosures

Abstract Background Although uncommon, nontuberculous mycobacterial infections (NTMI) of the upper extremity cause significant morbidity based on their natural history, delay in diagnosis, prolonged duration of antimicrobial therapy often combined with surgical debridement, and functional loss. Herein we describe our experience with such infections. Methods Records for adult patients from two academic, tertiary facilities with culture-proven NTMI involving the upper extremity were retrospectively reviewed. Demographic information, co-morbidities, laboratory and microbiological evaluation, management, and outcomes were extracted. Patients were analyzed based on pathogen identified and immune suppression. Results 77 patients were identified. The mean age was 59 years and 65% of patients were male. 48% reported a preceding injury, with the hand being most frequently involved (58%). 41% were considered immune compromised; 19% of them were organ transplant recipients. Mean symptom duration prior to presentation was 203 days. Mean time to culture identification was 33 days, and 25 different species of NTM were identified (subcategorized as rapid or slow growers). 77% had solitary lesions, with cutaneous/subcutaneous location as the most common site. All patients underwent surgical debridement with four undergoing amputation to control infection. 69% received combination antimicrobial therapy for a mean duration of 184 days. Immunosuppressed patients were treated with antimicrobial therapy for a longer duration (mean 243 vs 155 days). One-third of patients experienced complications and/or recurrence regardless of organism type. Conclusion NTMI of the upper extremity is often misdiagnosed leading to significant delays in appropriate management. Knowledge of its protean manifestations and early consideration in the differential diagnosis of chronic, painful swelling of the hand or wrist, nodular or inflammatory lesions, or septic arthritis is crucial. A low threshold for surgical or biopsy with specimens sent for histopathology as well as microbiologic analysis is warranted. A combined approach with surgical debridement and prolonged combination antimicrobial therapy is necessary for optimal outcomes; however, adverse reactions from such therapy are commonly encountered. Disclosures All Authors: No reported disclosures

Abstract Background Management of disseminated Nocardia (NC) infection in transplant recipients requires prolonged antimicrobial therapy. Treatment can be particularly challenging if NC is resistant to standard agents. Drug toxicities can further limit options. We present a series of transplant patients with multi-drug resistant, disseminated NC infection complicated by serious adverse reactions to sequential antimicrobials. Methods This is a prospective review monitoring response to treatment of disseminated NC as well as adverse events to therapies. Results The first case is a 66-year old heart transplant patient who presented with fever and cough. Investigations revealed N. otitidiscaviarum lung lesion and multiple brain abscesses. Trimethoprim-sulfamethoxazole (TMP-SMX) and linezolid were started empirically. NC was fully susceptible to linezolid only, and intermediate to quinolones and tobramycin. Linezolid was switched to ciprofloxacin due to ongoing cytopenia, and dose of TMP-SMX was reduced due to renal insufficiency. Repeat brain MRI showed enlarging abscesses; regimen was changed to linezolid and moxifloxacin. Severe peripheral neuropathy led to linezolid discontinuation and initiation of high-dose doxycycline plus moxifloxacin. One year into therapy, he presented with a large aortic dissection. His long-term quinolone therapy was felt to be contributory. He underwent aortic stent placement and remains on doxycycline monotherapy. The second case is a 74-year old female renal transplant patient who presented with fevers. A perinephric abscess was found which grew N. farcinica resistant to floroquinolones and clarithromycin, and intermediate to doxycycline. Further imaging also revealed pulmonary and brain involvement. TMP-SMX was started but soon switched to linezolid due to acute kidney injury. One month later she presented with severe thrombocytopenia and subdural hematoma thought to be secondary to linezolid. She died despite surgery. Conclusion This series illustrates challenges encountered in the treatment of disseminated NC infection in transplant recipients. Multidrug resistant NC coupled with serious toxicities of therapies often severely limits treatment options. Counseling patients and closely monitoring for adverse events is essential. Disclosures All Authors: No reported disclosures

Abstract Most patients with coronavirus disease 2019 (COVID-19) have mild to moderate illness not requiring hospitalization. However, no study has detailed the evolution of symptoms in the first month of illness. At our institution, we conducted remote (telephone and video) visits for all adult outpatients diagnosed with COVID-19 within 24 h of a positive nasopharyngeal polymerase chain test for SARS-CoV-2. We repeated regular video visits at 7, 14, and 28 days after the positive test, retrospectively reviewed the prospective data collected in the remote visits, and constructed a week by week profile of clinical illness, through week 4 of illness. We reviewed the courses of 458 symptomatic patients diagnosed between March 12, 2020, and June 22, 2020, and characterized their weekly courses. Common initial symptoms included fever, headache, cough, and chest pain, which frequently persisted through week 3 or longer. Upper respiratory or gastrointestinal symptoms were much shorter lived, present primarily in week 1. Anosmia/ageusia peaked in weeks 2 to 3. Emergency department visits were frequent, with 128 visits in the 423 patients who were not hospitalized and 48 visits among the 35 outpatients (7.6%) who were eventually hospitalized (2 subsequently died). By the fourth week, 28.9% said their illness had completely resolved. After the 4-week follow up, 20 (4.7%) of the 423 nonhospitalized patients had further medical evaluation and management for subacute or chronic COVID-19 symptoms. Mild to moderate outpatient COVID-19 is a prolonged illness, with evolving symptoms commonly lasting into the fourth week of illness.

Herein, we report a case of a 68-year-old woman receiving ibrutinib for chronic lymphocytic leukaemia, who presented with septic shock and a progressive necrotic lesion on her nose. Surgical pathology of the nasal lesion revealed evidence of tissue necrosis, and both tissue and blood culture grew Pseudomonas aeruginosa. A diagnosis of ecthyma gangrenosum was made. Additional investigations also led to the discovery of invasive pulmonary aspergillosis. To our knowledge, this is the first case of ecthyma gangrenosum secondary to Pseudomonas sepsis and concurrent invasive pulmonary aspergillosis associated with ibrutinib use.

Abstract Background Infective endocarditis (IE) is the most feared complication of Staphylococcus aureus bacteremia (SAB). Transesophageal echocardiogram (TEE) is generally recommended for all patients with SAB; however, supporting data for this are limited. We previously developed a scoring system, “PREDICT,” that quantifies the risk of IE and identifies patients who would most benefit most from undergoing TEE. The current prospective investigation aims to validate this score. Methods We prospectively screened all consecutive adults (≥18 years) hospitalized with SAB at 3 Mayo Clinic sites between January 2015 and March 2017. Results Of 220 patients screened, 199 with SAB met study criteria and were included in the investigation. Of them, 23 (11.6%) patients were diagnosed with definite IE within 12 weeks of initial presentation based on modified Duke’s criteria. Using the previously derived PREDICT model, the day 1 score of ≥4 had a sensitivity of 30.4% and a specificity of 93.8%, whereas a day 5 score of ≤2 had a sensitivity and negative-predictive value of 100%. Additional factors including surgery or invasive procedure in the past 30 days, prosthetic heart valve, and higher number of positive blood culture bottles in the first set of cultures were associated with increased risk of IE independent of the day 5 risk score. Conclusions We validated the previously developed PREDICT scoring tools for stratifying risk of IE, and the need for undergoing a TEE, among cases of SAB. We also identified other factors with predictive potential, although larger prospective studies are needed to further evaluate possible enhancements to the current scoring system.

Abstract We report 8 cases of coccidioidomycosis associated with ruxolitinib treatment. Among 135 patients living in the coccidioidal-endemic region receiving ruxolitinib, 5 cases were diagnosed after starting and 4 had extrathoracic dissemination. Periodic serological screening while on ruxolitinib is warranted for patients residing in the coccidioidal-endemic region.

AbstractTransmission of tuberculosis (TB) from a deceased solid organ donor to recipients can result in severe morbidity and mortality. In 2018, four solid organ transplant recipients residing in three states but sharing a common organ donor were diagnosed with TB disease. Two recipients were hospitalized and none died. The organ donor was born in a country with a high incidence of TB and experienced 8 weeks of headache and fever prior to death, but was not tested for TB during multiple hospitalizations or prior to organ procurement. TB isolates of two organ recipients and a close contact of the donor had identical TB genotypes and closely related whole‐genome sequencing results. Donors with risk factors for TB, in particular birth or residence in countries with a higher TB incidence, should be carefully evaluated for TB.

Herein we report a case of a 67-year-old man with chronic lymphocytic leukaemia who developed acute onset of fever and altered mental status while receiving ibrutinib therapy. He was eventually found to have Capnocytophaga canimorsus meningitis. Timely diagnosis and appropriate antimicrobial therapy was associated with a favourable outcome. We describe challenges associated with appropriate identification of, and briefly review infections caused by Capnocytophaga sp. To our knowledge, this is the first case of invasive C. canimorsus infection in the setting of ibrutinib therapy, and adds to the growing list of serious infections that have been associated with this agent.

Abstract Background Cardiac implantable electronic device-related infective endocarditis (CIED-IE) comprises 10–57% of total CIED infections. Patients with definite CIED-IE who fulfill both major modified Duke criteria have not been well characterized. Methods Data from the Multicenter Electrophysiologic Device Infection Cohort, a prospective, multinational study of CIED infections were used to describe a subset of patients with CIED-IE who met both major Duke criteria for definite IE (bloodstream infection and intracardiac vegetations [VEG]). Results Of 433 patients with CIED infection, 144 (33.3%) had definite CIED-IE. The median age was 68 years and 77.1% were male. Twelve (8.3%) had past CIED infection. Seventy-seven patients (53.5%) had permanent pacemakers, 38 (26.4%) had implantable cardioverter defibrillators, and 29 (20.1%) had combination devices. The median time following the last device procedure was 550 days. CIED-IE was early in 60 patients (41.7%) and late in 84 (58.3%). Most patients presented with fever (77.8%) and sepsis (44.4%) with a median symptom duration of 7 days. On echocardiography, lead VEG was noted in 125 patients (86.8%) and valvular VEG in 54 patients (37.5%) with the tricuspid valve involved in 56.5%. On the basis of VEG location, there were 90 patients (62.5%) with isolated lead-associated IE (LAE), 19 patients (13.2%) with isolated valve-associated IE (VAE), and 35 patients (24.3%) with both (LVAE). All patients had positive blood cultures and 63/119 (52.9%) had positive lead cultures. The predominant organism in blood was Staphylococcus aureus (42.4%), followed by coagulase-negative staphylococci (20.1%). CIED removal occurred in 131 patients (91%). There were 25 deaths during the index hospitalization and 34 total deaths (24.3%) by 6 months. Mortality correlated with age >75 (P = 0.023) and sepsis on presentation (P = 0.052). Infecting organism, site of VEG, and device removal did not impact the risk of death. Conclusion Definite CIED-IE is relatively common. The majority of patients tend to have late-onset infection and often present with sepsis. S. aureus is the dominant organism causing definite CIED-IE. Isolated LAE occurs in 63% of patients. Older age and sepsis on admission are associated with higher mortality. Disclosures All authors: No reported disclosures.