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Background Echinocandins are first-line therapy of candidemia with an option to de-escalate (DE) to oral azoles based on clinical response and susceptibilities. There are no universally accepted DE criteria but rapid diagnostic testing (RDT) allows for earlier Candida sp. identification. The objective of this study was to compare outcomes between early DE (≤ 2 days) and late DE ( > 2 days) using RDT as an antifungal stewardship strategy. Methods This was a retrospective study in adults with candidemia caused by C. albicans, C. tropicalis, and C. parapsilosis from 2017-2021. Patients with neutropenia or deep-seated/uncontrolled source were excluded. Primary outcome was 30-day global response (clinical and microbiological success). Secondary outcomes included clinical and microbiologic success, length of stay after candidemia, development of resistance, infection recurrence, and mortality. Comparisons were performed using Chi-squared or Fischer’s exact test for categorical variables and Student’s t test or Mann-Whitney U for continuous variables. A multivariable logistic regression model was constructed to identify independent factors for global response using DE strategy, ICU status, and considering all variables with a p-value < 0.1 on univariate analysis. Results 87 patients were included, 34 (39%) in early DE group and 53 (61%) in late DE group. Groups were well matched except early DE patients were less likely to be in the ICU at time of candidemia (18% vs 38%; p=0.079). C. albicans was the most common Candida sp. (54%) and a vascular catheter was the most common source (45%). Overall global response was 93% with an in-hospital mortality of 8%. At the time of DE, 45% were considered hemodynamically unstable. No difference in global response between early and late DE was identified (94% vs 96%, p=1.0). On multivariable analysis, no independent predictors were identified and late DE was not associated with improved global response [OR 0.82 (95% CI 0.08, 8.24)]. No differences were identified in secondary outcomes. Conclusion There were no differences in outcomes between early and late DE in the treatment of azole-susceptible candidemia. Early DE within 2 days based on rapid species identification should be considered as an antifungal stewardship strategy based on local susceptibilities. Disclosures All Authors: No reported disclosures.

The prevalence of antimicrobial resistance among many common bacterial pathogens is increasing. The emergence and global dissemination of these antibiotic-resistant bacteria (ARB) is fuelled by antibiotic selection pressure, inter-organism transmission of resistance determinants, suboptimal infection prevention practices and increasing ease and frequency of international travel, among other factors. Patients with chronic kidney disease, particularly those with end-stage renal disease who require dialysis and/or kidney transplantation, have some of the highest rates of colonization and infection with ARB worldwide. These ARB include methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus spp. and several multidrug-resistant Gram-negative organisms. Antimicrobial resistance limits treatment options and increases the risk of infection-related morbidity and mortality. Several new antibiotic agents with activity against some of the most common ARB have been developed, but resistance to these agents is already emerging and highlights the dire need for new treatment options as well as consistent implementation and improvement of basic infection prevention practices. Clinicians involved in the care of patients with renal disease must be familiar with the local epidemiology of ARB, remain vigilant for the emergence of novel resistance patterns and adhere strictly to practices proven to prevent transmission of ARB and other pathogens.

Infectious diarrhea following hematopoietic cell transplantation (HCT) significantly contributes to morbidity and mortality. Most HCT recipients experience diarrhea in the post-transplantation period, and infectious pathogens are frequently detected during diarrheal episodes. However, little is known about how frequently these patients are colonized with gastrointestinal (GI) pathogens before their transplantation and whether colonization predicts future diarrheal illness. We sought to determine how frequently HCT recipients are colonized with GI pathogens before HCT and the degree to which pre-HCT colonization predicts post-transplantation infectious diarrheal illness. We conducted a prospective cohort study of allogeneic and autologous HCT recipients at a single center between December 2016 and January 2019. Stool samples were collected during the week before HCT, and formed samples were evaluated for the presence of 22 diarrheal pathogens using the BioFire FilmArray GI panel. We determined the frequency with which participants were colonized with each pathogen and identified factors associated with colonization. We then determined how frequently pretransplantation colonization led to post-transplantation diarrheal infections due to the colonizing pathogen and whether colonization was associated with increased number of days of post-transplantation diarrhea during the transplant hospitalization. We enrolled 112 asymptomatic patients (allogeneic, 61%; autologous, 39%) who had a formed stool specimen before HCT, of whom 41 (37%) had a GI pathogen detected. The most commonly detected organisms were Clostridioides difficile (n = 21; 19%), Yersinia enterocolitica (n = 9; 8%), enteropathogenic Escherichia coli (EPEC) (n = 6; 6%), and norovirus (n = 5; 4%). Female sex and previous C. difficile infection were associated with C. difficile colonization, and having non-Hodgkin lymphoma was associated with being colonized with a diarrheal pathogen other than C. difficile. Thirteen of 21 patients (62%) with pretransplantation C. difficile colonization developed a clinical C. difficile infection post-transplantation, and 8 of 10 patients (80%) colonized with EPEC or enteroaggregative E. coli developed post-transplantation infections due to their colonizing pathogen. Pretransplantation C. difficile colonization was also associated with an increased duration of post-transplantation diarrhea (P = .048). Conversely, none of the 9 patients with pretransplantation Yersinia enterocolitica colonization developed a post-transplantation Y. enterocolitica infection. Patients admitted for HCT are frequently colonized with a diverse range of GI pathogens. Colonization with C. difficile colonization and diarrheagenic E. coli is frequently associated with post-transplantation diarrheal infections caused by these organisms, but the clinical significance of colonization with other GI pathogens is not clear.

Background Kidney graft recipients receiving immunosuppressive therapy may be at heightened risk for coronavirus disease 2019 (Covid-19) and adverse outcomes. It is therefore important to characterize the clinical course and outcome of Covid-19 in this population and identify safe therapeutic strategies. Methods We performed a retrospective chart review of 73 adult kidney graft recipients evaluated for Covid-19 from 13 March to 20 April 2020. Primary outcomes included recovery from symptoms, acute kidney injury, graft failure and case fatality rate. Results Of the 73 patients screened, 54 tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)—39 with moderate to severe symptoms requiring hospital admission and 15 with mild symptoms managed in the ambulatory setting. Hospitalized patients were more likely to be male, of Hispanic ethnicity and to have cardiovascular disease. In the hospitalized group, tacrolimus dosage was reduced in 46% of patients and mycophenolate mofetil (MMF) therapy was stopped in 61% of patients. None of the ambulatory patients had tacrolimus reduction or discontinuation of MMF. Azithromycin or doxycycline was prescribed at a similar rate among hospitalized and ambulatory patients (38% versus 40%). Hydroxychloroquine was prescribed in 79% of hospitalized patients. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%) and 7 patients died, resulting in a case fatality rate of 13% among Covid-19-positive patients and 18% among hospitalized Covid-19-positive patients. Conclusions Data from our study suggest that a strategy of systematic triage to outpatient or inpatient care, early management of concurrent bacterial infections and judicious adjustment of immunosuppressive drugs rather than cessation is feasible in kidney transplant recipients with Covid-19.

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative therapy for a variety of malignant and nonmalignant hematologic disorders, but its efficacy is limited by transplant-rel...

BackgroundOrgan graft recipients receiving immunosuppressive therapy are likely to be at heightened risk for the Coronavirus Disease 2019 (Covid-19) and adverse outcomes including death. It is therefore important to characterize the clinical course and outcome of Covid-19 in this vulnerable population and identify therapeutic strategies that are safe.MethodsWe performed a retrospective chart review of 54 adult kidney transplant patients diagnosed with Covid-19 and all managed in New York State, the epicenter of Covid-19 pandemic. All 54 patients were evaluated by video visits, or phone interviews, and referred to our Fever Clinic or Emergency Room for respiratory illness symptoms consistent with Covid-19 and admitted if deemed necessary from March 13, 2020 to April 20, 2020. Characteristics of the patients were stratified by hospitalization status and disease severity. Clinical course including alterations in immunosuppressive therapy were retrieved from their electronic medical records. Primary outcomes included recovery from Covid-19 symptoms, acute kidney injury, graft failure, and case fatality rate.ResultsOf the 54 SARS-Cov-2 positive kidney transplant recipients, 39 with moderate to severe symptoms were admitted and 15 with mild symptoms were managed at home. Hospitalized patients compared to non-hospitalized patients were more likely to be male, of Hispanic ethnicity, and to have cardiovascular disease. At baseline, all but 2 were receiving tacrolimus, mycophenolate mofetil (MMF) and 32 were on a steroid free immunosuppression regimen. Tacrolimus dosage was reduced in 46% of hospitalized patients and maintained at baseline level in the non-hospitalized cohort. Mycophenolate mofetil (MMF) dosage was maintained at the baseline dosage in 11% of hospitalized patients and 64% of non-hospitalized patients and was stopped in 61% hospitalized patients and 0% in the non-hospitalized cohort. Azithromycin or doxycycline were prescribed at a similar rate among hospitalized and non-hospitalized patients (38% vs. 40%). In addition, 50% of hospitalized patients were treated for concurrent bacterial infections including pneumonia, urinary tract infections and sepsis. Hydroxychloroquine was prescribed in 79% of hospitalized patients and only one of 15 non-hospitalized patients. Acute kidney injury occurred in 51% of hospitalized patients. Patients with severe disease were more likely to have elevations in inflammatory biomarkers at presentation. At a median of 21 days follow up, 67% of patients have had their symptoms resolved or improved and 33% have persistent symptoms. Graft failure requiring hemodialysis occurred in 3 of 39 hospitalized patients (8%). Three of 39 (8%) hospitalized patients expired and none of the 15 non-hospitalized patients expired.ConclusionsClinical presentation of Covid-19 in kidney transplant recipients was similar to what has been described in the general population. The case fatality rate in our entire cohort of 54 kidney transplant recipients was reassuringly low and patients with mild symptomology could be successfully managed at home. Data from the our study suggest that a strategy of systematic screening and triage to outpatient or inpatient care, close monitoring, early management of concurrent bacterial infections and judicious use of immunosuppressive drugs rather than cessation is beneficial.

Solid organ transplant recipients may be at a high risk for SARS-CoV-2 infection and poor associated outcomes. We herein report our initial experience with solid organ transplant recipients with SARS-CoV-2 infection at two centers during the first 3 weeks of the outbreak in New York City. Baseline characteristics, clinical presentation, antiviral and immunosuppressive management were compared between patients with mild/moderate and severe disease (defined as ICU admission, intubation or death). Ninety patients were analyzed with a median age of 57 years. Forty-six were kidney recipients, 17 lung, 13 liver, 9 heart, and 5 dual-organ transplants. The most common presenting symptoms were fever (70%), cough (59%), and dyspnea (43%). Twenty-two (24%) had mild, 41 (46%) moderate, and 27 (30%) severe disease. Among the 68 hospitalized patients, 12% required non-rebreather and 35% required intubation. 91% received hydroxychloroquine, 66% azithromycin, 3% remdesivir, 21% tocilizumab, and 24% bolus steroids. Sixteen patients died (18% overall, 24% of hospitalized, 52% of ICU) and 37 (54%) were discharged. In this initial cohort, transplant recipients with COVID-19 appear to have more severe outcomes, although testing limitations likely led to undercounting of mild/asymptomatic cases. As this outbreak unfolds, COVID-19 has the potential to severely impact solid organ transplant recipients.

Background Carbapenemase gene-positive organisms (CPOs) are associated with infections with high mortality rates and have the potential to facilitate epidemic spread of carbapenem resistance. Passive reporting to CDC identified CPOs among organ transplant recipients, potentially representing an emerging reservoir for spread. We aimed to determine the prevalence of CPOs in hospital units where solid organ transplant (SOT) recipients receive care in order to inform public health action to prevent transmission. Methods All healthcare facilities identified one medical unit where SOT recipients received inpatient care and conducted point prevalence surveys (PPS) of all consenting patients on 1-2 designated calendar days. We used the Cepheid Xpert® Carba-R assay to identify carbapenemase genes (blaKPC, blaNDM, blaVIM, blaIMP, blaOXA-48) from rectal swabs; carbapenemase-positive swabs were cultured for organisms. All laboratory testing was conducted at the Wadsworth Center, part of CDC’s Antibiotic Resistance Laboratory Network. Results Five participating hospitals performed nine PPS from September 2019 through June 2020. In total, 154 patients were screened and 92 (60%) were SOT recipients (Table). The most common transplanted organs were kidney (44, 48%) and liver (39, 42%). Carbapenemase genes were detected among 5 (5%) SOT recipients, all from a single healthcare facility; 4 (80%) were blaKPC and 1 (20%) was blaNDM. Of the positive specimens cultured, blaKPC was carried by Enterobacter cloacae complex (ECC), Klebsiella pneumoniae, and Klebsiella oxytoca and blaNDM was carried by K. oxytoca; blaKPC was carried by both ECC and K. pneumoniae in a single individual. For SOT patients with CPOs, the median interval from transplantation to swab collection was 108 days (range: 12 to 323). CPOs were only detected in 1 (2%) of 62 non-transplant patients. TABLE Characteristics of Carbapenemase Gene-positive Organism (CPO) Pilot Surveillance Participants Conclusion Among participating facilities, most did not identify CPOs among patients admitted to transplant units. These findings represent a small number of patients and facilities; additional PPS in areas with varied CPO epidemiology are needed to understand whether SOT recipients should be routinely screened for CPOs. Disclosures All Authors: No reported disclosures

Background Limited data are available for risk assessment and outcome of COVID-19 in patients with hematologic malignancies (HM). We present a single center study of COVID-19 pneumonia in a cohort of 31 patients with HM. Methods Data were abstracted from electronic medical records for patients admitted to NYPH between 3/5/20 and 4/17/20 and entered into a REDCap database. Results Twenty (64.5%) were male; median age was 71 years. There were 8 patients with Multiple Myeloma (MM), 8 with Chronic Lymphocytic Leukemia (CLL), 6 (19.4%) had AML, 5 (16.1%) NHL, 2 (3.2%) ALL; CML, MDS and Polycythemia Vera occurred in 1 patient each. Twenty-four (77.4%) had active HM; 6 (19.4%) were in remission; and 1 relapsed. Nineteen patients (61.3%) received recent chemotherapy and 11 (35.5%) immunosuppressive therapies. There were 7 (22.6%) hematopoietic stem cell transplant (HSCT) recipients (4 allogeneic and 3 autologous). Comorbidities were evenly distributed among all malignancies: 18 (58.1%) had hypertension, 9 (38.7%) obesity, 7 (22.6%) diabetes mellitus, and 11 (35.5%) were former smokers. The most common symptoms included cough (90.3%), fever (83.9%) and dyspnea (61.3%); 7 (22.6%) had nausea and vomiting; 7 (22.6%) had diarrhea. On presentation, hypoxia (O2 sat ≤94% on room air) occurred in 64.5%; median ALC was 330/ml; 23 (74.2%) had ALC< 1000/ml; median CRP was 15.9 mg/dl (2.5–40.4), ferritin 1162 ng/ml (264 - > 16500), and D-dimers 456 ng/ml (< 150–2418). Thirteen patients (41.9%) required ICU admission and were intubated; among those 9 (69.2%) had either MM or CLL. Co-infections were uncommon; two patients developed HSV1 pneumonitis and one of these also had CMV pneumonitis. Twenty-eight (90.3%) were treated with hydroxychloroquine, 5 (16.1%) remdesivir, 2 (6.5%) tocilizumab, 1 (3.2%) sarilumab, and 4 (12.9%) with methylprednisolone 0.5mg/kg Q12h. Seventeen patients (54.8%) recovered and were discharged, 12 (38.7%) died; 2 (6.5%) were still hospitalized but left the ICU. Conclusion In our cohort, there were predominantly more patients with MM and CLL and 56% of these were intubated; larger cohort studies will further define the risk and outcome for COVID-19 in patients with HM. Disclosures Michael J. Satlin, MD, MS, Achaogen (Consultant)Allergan (Grant/Research Support)Merck (Grant/Research Support)Shionogi Inc. (Consultant)