Background The optimal duration of empiric antimicrobial therapy in febrile neutropenia of unknown origin is unclear. This study evaluated outcomes in autologous and allogeneic hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin who received early de-escalation of broad-spectrum antimicrobials prior to hematopoietic recovery versus those who continued broad-spectrum antimicrobials until hematopoietic recovery. Methods A single-center, retrospective study assessed hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin. Patients were categorized into either cohort 1, representing early de-escalation prior to hematopoietic recovery, or cohort 2, representing continuation of broad-spectrum antimicrobials until hematopoietic recovery. Results A total of 107 patients were included (22.4% in cohort 1 and 77.6% in cohort 2). Most patients (87.5%) in cohort 1 underwent haploidentical hematopoietic cell transplantation, whereas 84.3% of patients in cohort 2 received autologous hematopoietic cell transplantation. There were no significant differences in rates of recurrent fever (4.2% versus 7.2%, in cohorts 1 and 2, respectively, adjusted odds ratio = 0.84, P = 0.85), re-escalation (4.2% versus 4.8%, adjusted odds ratio = 1.57, P = 0.64), and Clostridioides difficile-associated infections (4.2% versus 2.4%, adjusted odds ratio = 2.27, P = 0.43). No patient experienced in-hospital mortality, intensive care unit admission, or bacteremia. Conclusion Hematopoietic cell transplantation recipients with febrile neutropenia of unknown origin in which broad-spectrum antimicrobials were de-escalated prior to hematopoietic recovery did not experience adverse outcomes. These results concur with recently published studies and the Fourth European Conference on Infections in Leukemia guidelines. An early de-escalation approach in haploidentical hematopoietic cell transplantation recipients specifically appears safe and may result in a reduction in antimicrobial utilization.

Background: Guideline recommendations from the Infectious Diseases Society of America (IDSA) and the 4th European Conference on Infections in Leukemia (ECIL-4) for the optimal duration of empiric antimicrobial therapy in patients with hematological malignancies and febrile neutropenia (FN) of unknown origin (FUO) vary given limited available evidence. Recent studies involving hematology patients and hematopoietic cell transplantation (HCT) recipients with FN have demonstrated that de-escalation of broad-spectrum antimicrobials (BSA) prior to hematopoietic recovery is associated with greater antibiotic-free days, but without increased risks, such as recurrent fever, bacteremia, intensive care unit (ICU) admission, or inpatient mortality. However, the safety of this de-escalation approach has not been extensively studied in autologous and haploidentical HCT recipients within the United States as most prior studies were conducted in Europe. The main purpose of this study was to compare rates of recurrent fever, re-escalation of therapy, and Clostridium difficile-associated infection (CDI) in autologous and allogeneic HCT recipients with FUO who received early de-escalation of BSA prior to hematopoietic recovery versus those who continued BSA until hematopoietic recovery. Methods: This retrospective, observational study assessed HCT recipients with FN admitted to Carolinas Medical Center in Charlotte, North Carolina between March 2014 to April 2018. Patients were included if they were ≥ 18 years of age, had an active hematologic malignancy and underwent allogeneic or autologous HCT, experienced their first episode of FN after HCT, and were initiated on appropriate BSA for ≥ 48 hours. Patients were excluded if they had microbiological or radiological diagnosis of active bacterial, fungal, or viral infection during the FN episode. Patients were enrolled into either cohort 1, which represented patients who were de-escalated to prophylactic antimicrobials prior to hematopoietic recovery (early de-escalation group), or cohort 2, which represented patients who continued BSA until hematopoietic recovery (hematopoietic recovery de-escalation group). Fisher's exact test was conducted to make cohort comparisons for categorical patient characteristics, while Mann-Whitney U test was employed for continuous variables. Multivariate logistic regression was utilized to evaluate rates of recurrent fever, re-escalation of therapy, and CDI between the 2 cohorts. Results: A total of 107 patients were included with 24 (22.4%) in cohort 1 and 83 (77.6%) in cohort 2. Most patients (87.5%) in cohort 1 received haploidentical HCT, whereas 84.3% of patients in cohort 2 received autologous HCT (P < 0.001). The median duration of neutropenia following the first FN episode was significantly shorter in cohort 2 (15 vs 4 days in cohorts 1 and 2, respectively, P < 0.001). There were no significant differences in rates of recurrent fever (4.2% vs 7.2%, adjusted OR (AOR) = 0.63,P = 0.684) and re-escalation of therapy (4.2% vs 4.8%, AOR = 1.26, P = 0.853) within 72 hours following de-escalation between the 2 cohorts. Rates of CDI within 30 days from hematopoietic recovery were also similar (4.2% vs 2.4%, AOR = 2.25, P = 0.582). No patients experienced inpatient mortality, ICU admission, or bacteremia. There were no significant differences in days of antimicrobial use per 1000 transplant days (P = 0.071). In a subgroup analysis of only allogeneic HCT recipients, haploidentical was the most common transplant type with 91.3% (n = 21/23) in cohort 1 and 69.2% (n = 9/13) in cohort 2. Recurrent fever was very infrequent among allogeneic HCT recipients (n = 1 in cohort 1 vs n = 0 in cohort 2, P > 0.999). However, a significant reduction in days of antimicrobial use per 1000 transplant days (P = 0.002) was observed in cohort 1 compared to cohort 2. Conclusion: HCT recipients with FUO who received de-escalation of BSA prior to hematopoietic recovery did not experience increased rates of recurrent fever, re-escalation of therapy, CDI, bacteremia, ICU admission, or inpatient mortality. These results concur with recently published studies and the ECIL-4 guidelines. An early de-escalation approach in haploidentical HCT recipients specifically appears to be safe and may result in a reduction in antimicrobial utilization. Disclosures Grunwald: Forma Therapeutics: Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Ariad: Consultancy, Membership on an entity's Board of Directors or advisory committees; Cardinal Health: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech: Research Funding; Incyte Corporation: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Medtronic: Equity Ownership; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Alexion: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Research Funding; Merck: Consultancy, Membership on an entity's Board of Directors or advisory committees. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees. Usmani:Amgen, BMS, Celgene, Janssen, Merck, Pharmacyclics,Sanofi, Seattle Genetics, Takeda: Research Funding; Abbvie, Amgen, Celgene, Genmab, Merck, MundiPharma, Janssen, Seattle Genetics: Consultancy.

Antibiotic overuse is high in patients hospitalized with coronavirus disease 2019 (COVID-19) despite a low documented prevalence of bacterial infections in many studies. In this study evaluating 65 COVID-19 patients in the intensive care unit, empiric broad-spectrum antibiotics were often overutilized with an inertia to de-escalate despite negative culture results.

Background Candida species are the most common cause of fungemia and are associated with high mortality. Management concordant with the Infectious Diseases Society of America guidelines and infectious diseases consultation (IDC) have been shown to lower mortality in patients with candidemia. The purpose of this study was to compare in-hospital mortality at a large multi-site healthcare system, including sites providing IDC via telemedicine services, in patients with candidemia with and without IDC. Methods This was a retrospective, observational cohort study completed at ten sites of Legacy Atrium Health in Charlotte Metro, NC, USA; at five sites, IDC is performed via telemedicine. Adult hospitalized patients identified with candidemia were enrolled May 2018-June 2019. The primary outcome was in-hospital mortality of IDC and non-IDC patients. Secondary outcomes included obtainment of repeat blood cultures, receipt of antifungal treatment, duration of therapy, removal of central venous lines (CVC) when present, and ophthalmological examination. Fisher’s exact, Chi-Square, or two-tailed Student’s t-test were used for demographics, primary and secondary outcomes as appropriate. Results A total of 126 patients were enrolled: 103 (82%) in the IDC group and 23 (18%) in the non-IDC group (Table 1). Mortality was significantly lower, and rates of repeat blood culture obtainment and receipt of antifungal treatment were significantly higher in patients with IDC (Table 2). Other outcomes including duration of therapy, removal of CVC, repeat cultures within 48 hours, and ophthalmological examination were not statistically different between groups. Conclusion This study is the first multi-site healthcare system providing telemedicine services to evaluate the impact of IDC on candidemia mortality. Ophthalmological examination rates were low in both groups, highlighting a potential area for improvement. IDC had significantly lower mortality, higher rates of antifungal treatment, and higher rates of repeat blood culture obtainment. IDC should be strongly considered in all patients with candidemia. Disclosures All Authors: No reported disclosures

Background Studies have shown the proportion of critically ill patients with COVID-19 receiving empiric antibiotics (ABX) greatly exceeds those with culture-proven bacterial co-infections. However, the benefits of continuing ABX in culture-negative (CxN) cases is unknown; this practice may increase the risks associated with ABX overuse. The purpose of this study was to evaluate outcomes and antibiotic use (AU) in intensive care unit (ICU) patients with COVID-19 based on culture results. Methods This was a multicenter, retrospective cohort study evaluating adults in an ICU for the first episode of ABX initiated following a confirmed COVID-19 diagnosis between September to December 2020. Blood and/or respiratory cultures must have been obtained within 24 hours (h) of ABX initiation. Patients were categorized into three groups: 1) CxN, ABX discontinued ≤ 72 h, 2) CxN, ABX continued &gt; 72 h, or 3) Culture-positive (CxP). Data on AU was obtained from electronic medication administration records. The primary outcome was clinical success, defined as being discharged alive or &gt; 2-point decrease in the World Health Organization Clinical Progression Scale score from day of ABX initiation to day 30. Results A total of 65 patients were included with 35.4% being CxP. ABX were discontinued ≤ 72 h in 23.8% of CxN patients. Methicillin-susceptible Staphylococcus aureus was the most common organism in 52.2% of CxP patients (66.7% respiratory; 16.7% blood; 16.7% both). Anti-methicillin-resistant Staphylococcus aureus and anti-pseudomonal antibiotics were the most prescribed for the initial regimen (Table 1). ABX de-escalation occurred in 58.5% of patients. Initial ABX duration was significantly longer in the CxP group (P &lt; 0.01). No significant difference in clinical success was observed (Table 2). Although not significantly different, the highest rate of adverse events occurred in the CxN and ABX continued &gt; 72 h group (40.6%). Table 1. Antibiotic Use in ICU Patients with COVID-19 Table 2. Clinical Outcomes and Adverse Events in ICU Patients with COVID-19 Conclusion In ICU patients with COVID-19, empiric broad-spectrum ABX are often overutilized with an inertia to de-escalate despite negative culture results, potentially increasing the risk of adverse events. This remains an important area for focused antimicrobial stewardship efforts to mitigate the development of multidrug resistance. Disclosures Christopher Polk, MD, Atea (Research Grant or Support)Gilead (Advisor or Review Panel member, Research Grant or Support)Humanigen (Research Grant or Support)Regeneron (Research Grant or Support)