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Background The coronavirus-19-disease (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread to >200 countries and surpassed 7 million cases. There is a broad range of COVID-19 illness, ranging from milder disease to a rapidly progressive respiratory disease and ARDS. The causes of this different clinical course and the drivers for severe disease are currently unknown. A fulminant increase of pro-inflammatory cytokines is thought to play a role in causing a rapid disease evolution, however the immune correlates of severe COVID-19 remain unclear. Methods To gain insight into relationship between immune responses and disease severity we built a longitudinal cohort of 40 adult patients with known COVID-19. Samples were collected at diagnosis and every 7 days until hospital discharge or death. As controls we also included a group of convalescent patients, and subjects who tested negative for COVID-19 by PCR. Clinical and laboratory data and were also collected. Multicolor flow cytometry was used to determine the presence and phenotype of B, T and natural killer (NK) cells. We also identified specific sub-populations (Tfh, activated/cytotoxic CD8 and NK) and assessed lymphoid exhaustion of different cell types such as naïve, memory T cells, or NK over time. Anti-Sars-CoV2 IgG and IgM antibody were detected using lateral flow method. Results We found that the absolute number of lymphocytes and monocytes was decreased starting at diagnosis and correlated with disease severity. Disease severity correlated with decreased NK and T cell. In severe COVID-19 cases, NK cell populations were strongly decreased over time in intubated patients while they recovered in patients who improved and were discharged. CD8+ were also decreased at disease onset and seemed to correlate with disease severity. A high percentage of CD4+ and CD8+ T cells showed an exhausted phenotype. All patients tested at admission had IgM antibody responses irrespective of the course of the disease. Further analyses are ongoing. Conclusion The characterization and role of the immune responses in COVID-19 evolution is still under investigation. Further characterization of viral and immune factors will help in identifying subjects at high risk of severe disease and targets for intervention. Disclosures All Authors: No reported disclosures

Summary Objectives To determine the prevalence, risk factors, treatments, and outcomes of bloodstream infections (BSIs) due to carbapenem-resistant Enterobacteriaceae (CRE) in adult neutropenic patients with hematologic malignancies. Methods We reviewed all BSIs between 2008 and 2012 in this population at two New York City oncology centers. A case-control study was conducted to identify CRE BSI risk factors, using three controls of non-CRE BSIs per case. Results CRE caused 43 (2.2%) of 1992 BSIs overall and 4.7% of Gram-negative bacteremias. Independent risk factors for CRE BSI were prior β-lactam/β-lactamase inhibitor (adjusted odds ratio [aOR] 3.2; P = 0.03) or carbapenem (aOR 3.0; P = 0.05) use, current trimethoprim-sulfamethoxazole (aOR 24; P = 0.001) or glucocorticoid (aOR 5.4, P = 0.004) use, and having a prior CRE culture (aOR 12; P = 0.03). Patients with CRE bacteremia had a median of 52 h from culture collection until receipt of active therapy. They had a 51% BSI-related mortality rate, with a median of 4 days from bacteremia onset until death. CRE-active empirical therapy was associated with a lower 30-day mortality rate (17% vs. 59%; P = 0.08). Conclusions CRE are lethal emerging causes of bacteremia in neutropenic patients. New strategies are needed to shorten the delay in administration of CRE-active agents and improve outcomes in this vulnerable population.

After a cluster of fatal toxoplasmosis among stem cell transplant recipients at 2 hospitals, surveillance with polymerase chain reaction (PCR) (blood) was instituted. Rate of reactivation among seropositive recipients was 2.2 and 16%. Parasitemia was successfully managed with preemptive treatment. For seropositive recipients unable to take prophylaxis, toxoplasma PCR surveillance should be routinely performed.

Background The aim of this study is to describe the clinical manifestations, molecular mechanisms, and treatment outcomes of patients with echinocandin-resistant Candida tropicalis (C. tropicalis) bloodstream infections (BSI). Methods A PubMed search was conducted using the search terms related to C. tropicalis BSI and echinocandin resistance. Two previously unreported cases from our institution diagnosed with C. tropicalisBSI that developed resistance to echinocandins were also included. Demographics, comorbidities, treatment, clinical outcomes, and molecular mechanisms were analyzed. Results Seven patients with echinocandin-resistant C. tropicalis BSI were identified, including 5 previously reported cases and two from our institution. Median age was 58.7 ± 20.4 years; 3 (43%) patients were males. Three (43%) had acute myelogenous leukemia, 3 (43%) had acute lymphoblastic leukemia, and 1 (14%) had urothelial cancer. All patients were immunocompromised having received chemotherapy in the last six months and 3 (43%) were hematopoietic stem cell transplant recipients. Five (71%) had breakthrough of echinocandin resistance while receiving an echinocandin; one (14%) received caspofungin in the past 3 months and only one (14%) had no reported echinocandin exposure in the past 3 months. DNA sequencing of the FKS1 gene for mutations known to confer echinocandin resistance was performed in 4 cases, including our two index cases. Homozygous T-to-C mutations in two alleles of FKS1gene was detected in 2 cases, and a heterozygous mutation was detected in the other 2 cases, which resulted in a deduced serine-to-proline amino acid change at position 654 (S654P). Six patients (86%) survived after being treated with an antifungal agent other than an echinocandin. Treatment was changed to liposomal amphotericin B in two cases, and one each to voriconazole, fluconazole, voriconazole plus liposomal amphotericin B, and caspofungin plus voriconazole. The one patient who died received intravenous voriconazole. Conclusion Echinocandin resistance emerged in neutropenic patients with C. tropicalis fungemia through a characteristic mutational hot-spot amino acid change in the target FKS1 gene. Although alternative antifungal agents may be successfully used as salvage therapy, the outcome may still be fatal. Disclosures D. Perlin, Pfizer: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Astrellas: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Merck: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Cidara: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Synexis: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. F2G: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Myconostica: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Amplyx: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. Matinas: Research support, honoraria and/or consulting fees and/or has served on advisory board, Research support, honoraria and/or consulting fees and/or has served on advisory board. GAFFI: Scientific Advisor, Advisor. Bill and Melinda Gates Foundation: Scientific Advisor, Advisor

Background Fluoroquinolone (FQ) prophylaxis is widely used to prevent bloodstream infections (BSIs) in neutropenic patients undergoing hematopoietic stem cell transplantation (HCT). In order to assess whether increasing FQ resistance threatens the effectiveness of FQ prophylaxis, we screened HCT recipients for colonization with FQ-resistant Enterobacteriaceae (FQRE) and assessed the impact of colonization on the risk of BSI. Methods We collected stool samples on admission for HCT and weekly until neutrophil engraftment from patients at NewYork-Presbyterian Hospital/Weill Cornell Medical Center from November 2016 to March 2018. Patients received FQ prophylaxis during neutropenia. Perianal swabs were used when stool was unavailable. Stool and swab samples were plated onto MacConkey agar with 1 μg/mL ciprofloxacin, and colonies were identified and underwent antimicrobial susceptibility testing. We determined the prevalence of colonization with FQRE on admission for HCT, the risk of acquiring FQRE, and compared the risk of BSI during the transplant admission in colonized and noncolonized patients. Results We evaluated 178 HCT recipients and found that 35 (20%) had pre-transplant FQRE colonization (allogeneic: 20/89, 22%; autologous: 15/89, 17%). Thirty FQRE (86%) were Escherichia coli, 5 (14%) were Klebsiella pneumoniae, and 13 (37%) were extended-spectrum β-lactamase producers. Five (14%) of the 35 patients with pre-transplant FQRE colonization developed BSI due to an Enterobacteriaceae, and all bloodstream isolates had identical susceptibility profiles to the colonizing FQRE. In contrast, only one (1%) of 143 patients without pre-transplant FQRE colonization developed Enterobacteriaceae BSI (P = 0.001). Patients with pre-transplant FQRE colonization also had higher rates of any Gram-negative BSI (20% vs. 1%, P < 0.001), but did not have increased risk of Gram-positive BSI (6% vs. 11%, P = 0.5). Of 123 patients without initial FQRE colonization who had follow-up samples collected, 10 (8%) acquired FQRE during post-HCT neutropenia. Conclusion FQRE colonization is common on admission for HCT and is associated with decreased effectiveness of levofloxacin prophylaxis in preventing Gram-negative BSI during post-transplant neutropenia. Disclosures M. J. Satlin, Hardy Diagnostics: Grant Investigator, Research support; Allergan: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient; Biomerieux: Grant Investigator, Grant recipient; Achaogen: Consultant, Consulting fee. R. Malherbe, Hardy Diagnostics: Employee, Salary. S. G. Jenkins, Merck: Grant Investigator, Grant recipient. L. F. Westblade, Accelerate Diagnostics: Grant Investigator, Grant recipient; Biomerieux: Grant Investigator, Grant recipient; Allergan: Grant Investigator, Grant recipient; Merck: Grant Investigator, Grant recipient. T. J. Walsh, Merck: Grant Investigator, Research grant; Atellas: Consultant, Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Gilead: Scientific Advisor, Consulting fee; Allergan: Grant Investigator and Scientific Advisor, Consulting fee and Research grant; Scynexis: Grant Investigator, Research grant; Amplyx: Grant Investigator, Research grant; Shionogi: Scientific Advisor, Consulting fee.

Background Substance use during pregnancy often leads to involvement in the child welfare system, resulting in multiple social service systems and service providers working with families to achieve successful child welfare outcomes. The Vulnerable Infants Program of Rhode Island (VIP-RI) is a care coordination program developed to work with perinatal substance-users to optimize opportunities for reunification and promote permanency for substance-exposed infants. This paper describes services used by VIP-RI participants and child welfare outcomes. Methods Data collected during the first four years of VIP-RI were used to identify characteristics of program participants, services received, and child welfare outcomes: closed child welfare cases, reunification with biological mothers and identified infant permanent placements. Descriptive Results Medical and financial services were associated with positive child welfare outcomes. Medical services included family planning, pre- and post-natal care and HIV test counseling. Financial services included assistance with obtaining entitlement benefits and receiving tangible support such as food and clothing. Conclusions Findings from this study suggest services that address basic family needs were related to positive child welfare outcomes. The provision of basic services, such as health care and financial assistance through entitlement benefits and tangible donations, may help to establish a foundation so mothers can concentrate on recovery and parenting skills. Identification of services for perinatal substance users that are associated with more successful child welfare outcomes has implications for the child welfare system, treatment providers, courts and families.