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Antimicrobial stewardship programs (ASPs) have made immense strides in optimizing antibiotic, antifungal, and antiviral use in clinical settings. However, although ASPs are required institutionally by regulatory agencies in the United States and Canada, they are not mandated for transplant centers or programs specifically. Despite the fact that solid organ transplant recipients in particular are at increased risk of infections from multidrug-resistant organisms, due to host and donor factors and immunosuppressive therapy, there currently are little rigorous data regarding stewardship practices in solid organ transplant populations, and thus, no transplant-specific requirements currently exist. Further complicating matters, transplant patients have a wide range of variability regarding their susceptibility to infection, as factors such as surgery of transplant, intensity of immunosuppression, and presence of drains or catheters in situ may modify the risk of infection. As such, it is not feasible to have a “one-size-fits-all” style of stewardship for this patient population. The objective of this white paper is to identify opportunities, risk factors, and ASP strategies that should be assessed with solid organ transplant recipients to optimize antimicrobial use, while producing an overall improvement in patient outcomes. We hope it may serve as a springboard for development of future guidance and identification of research opportunities.

Background Despite multiple studies indicating a low prevalence of bacterial coinfection in coronavirus disease 2019 (COVID-19) patients, the majority of hospitalized COVID-19 patients receive one or more antibiotics. Patients with coinfection usually have multiple risk factors and poor clinical outcomes. Methods A retrospective case control study was conducted comparing clinical characteristics and antimicrobial use in hospitalized adult COVID-19 patients with bacterial co-infections vs. randomly selected patients without co-infections (matched on month of admission). The study was conducted at three hospitals within the Montefiore Medical Center, Bronx, NY between March 1, 2020 and October 31, 2020. A multivariable logistic regression model was developed to assess the relationship of each predictor variable with coinfection status. Secondary outcomes included hospital mortality, antibiotic days of therapy (DOT), and C. difficile infection. Results A total of 150 patients with coinfection and 150 patients without co-infection were included in the analysis. Table 1 summarized baseline characteristics and risk factors. The multivariable logistic regression model indicated that presence of a central line (OR=5.4, 95% CI: 2.7-11.1), prior antibiotic exposure within 30 days (OR=5.3, 95% CI: 2.8-10.0), prior ICU admission (OR=3.6, 95% CI: 1.7-7.6), steroid use (OR=2.7, 95% CI: 1.4-4.9), and any comorbid condition (OR=2.7, 95% CI: 1.4-5.2) were significantly associated with the development of coinfection (table 2). Mortality was higher in patients with coinfection (56% vs. 11%, p < 0.0001) (table 3). Average antibiotic DOT was 10.5 in coinfected patients compared to 4 in non-coinfected patients, (p < 0.0001). Forty-one percent of coinfected patients had a multidrug resistant organism isolated. C. difficile rate was higher in coinfected patients (4% vs. 0%, p=0.03). Conclusion As the healthcare community contends with a 3rd year of COVID-19 pandemic, understanding risk factors most predictive of bacterial coinfection can guide empiric antimicrobial therapy and targeted stewardship interventions. Ideally, co-infection risk scores are developed which may be useful for future inpatient surges. Disclosures Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support Kelsie Cowman, MPH, Merck: Grant/Research Support.

Although infections are a significant potential complication among patients undergoing left ventricular assist device (LVAD) implantation, standardized surgical infection prophylaxis (SIP) regimens are not well defined. At Montefiore Medical Center, a 4-drug SIP regimen containing fluconazole, ciprofloxacin, rifampin, and vancomycin was previously utilized. In January 2020, the antimicrobial stewardship program implemented a 2-drug SIP regimen of vancomycin and cefazolin to limit exposure to broad-spectrum antibiotics. This study evaluated LVAD-associated infection rates prior to and following the SIP revision.A retrospective review of patients who underwent LVAD implantation from 1/2018 to 4/2021 was performed. Infections were classified using the International Society for Heart and Lung Transplantation definitions. Infection rates at 2 weeks, 30 days, and 90 days post-implantation in the 4-drug SIP regimen (1/2018-12/2019) and the 2-drug SIP regimen (1/2020 to 4/2021) were compared.A total of 71 patients were included. The number of patients with LVAD-associated infections (including surgical site infections) was not significantly different in either SIP group at 2 weeks (9% vs. 4%, p = .64), 30 days (9% vs. 11%, p = .99), or 90 days (19% vs. 14%, p = .75). There was no statistically significant difference in 30 or 90-day mortality. LVAD-associated gram-negative (7% vs. 7%; p .99) and fungal (5% vs. 0%; p = .51) infections were uncommon. The most common organism isolated was Staphylococcus aureus, and the most common type of infection was pneumonia in both SIP groups.No significant difference in LVAD-associated infections or infection-related mortality was observed with de-escalation of perioperative antibiotics. Additional studies with larger sample sizes are needed to endorse the findings of this study.

Objective Patients with coronavirus disease 2019 (COVID-19) can progress to a state of unregulated inflammation called cytokine storm syndrome (CSS). We describe formation and operation of a COVID-19 multidisciplinary consultation service that was allowed to individualize treatment for critically ill patients with COVID-19 during the pandemic. Methods Institutional experts from different subspecialties formed a COVID-19 CSS task force at Montefiore Medical Center, Bronx, NY. They agreed on a set of four clinical and six laboratory parameters that can help early identify COVID-19 CSS. We describe the formation and implementation of the COVID-19 task force. The case series description of the COVID-19 CSS consultation cohort highlights consultation volume, baseline characteristics, clinical and laboratory parameters, and how biologic treatments were allocated to these patients. Results Between April 4,2020, and May 7,2020, the COVID-19 CSS task force was formed, consisting of adult and pediatric rheumatologists and allergy and immunology physicians. The task force evaluated a total of 288 patients, of whom 197 (68%) were male, the median (interquartile range [IQR]) age was 62 (51-70) years, 122 (42%) were Hispanic, and 88 (31%) were Black or African American. The common presenting symptoms in all referred patients were dyspnea (85%) and diarrhea (80%). Thirty-one patients who received biologic therapy were younger, with a median (IQR) age of 53 (32-63) years, as opposed to 62.5 (52-70) years in the nonbiologic group (P = 0.008). A higher proportion receiving biologics was in the critical care setting (26 [84%] vs 151 [59%]; P = 0.006). Conclusion To the best of our knowledge, this is the first multidisciplinary collaborative effort to provide individualized patient recommendations for evaluation and treatment of patients with COVID-19 who may have CSS. This working model helped to devise an approach that may have identified patients who were most likely to benefit from biologic therapy in the absence of evidence-based guidelines.

We investigated the prevalence and clinical outcomes of COVID-19 in recipients of kidney transplants in the Bronx, New York, one of the epicenters of the pandemic. Between March 16 and June 2, 2020, 132 kidney transplant recipients tested positive by SARS-CoV-2 RT-PCR. From May 3 to July 29, 2020, 912 kidney transplant recipients were screened for SARS-CoV-2 IgG antibodies during routine clinic visits, of which 16.6% tested positive. Fifty-five of the 152 patients had previously tested positive by RT-PCR, while the remaining 97 did not have significant symptoms and had not been previously tested by RT-PCR. The prevalence of SARS-CoV-2 infection was 23.4% in the 975 patients tested by either RT-PCR or SARS-CoV-2 IgG. Older patients and patients with higher serum creatinine levels were more likely diagnosed by RT-PCR compared to SARS-CoV-2 IgG. Sixty-nine RT-PCR positive patients were screened for SARS-CoV-2 IgG antibodies at a median of 44 days post-diagnosis (Inter Quartile Range 31-58) and 80% were positive. Overall mortality was 20.5% but significantly higher (37.8% ) in the patients who required hospitalization. Twenty-three percent of the hospitalized patients required kidney replacement therapy and 6.3% lost their allografts. In multivariable analysis, older age, receipt of deceased-donor transplantation, lack of influenza vaccination in the previous year and higher serum interleukine-6 levels were associated with mortality. Thus, 42% of patients with a kidney transplant and with COVID-19 were diagnosed on antibody testing without significant clinical symptoms, 80% of patients with positive RT-PCR developed SARS-CoV-2 IgG and mortality was high among patients requiring hospitalization., Graphical abstract

The coronavirus pandemic has significantly impacted solid organ transplantation (SOT). Early in the outbreak period, transplant societies recommended suspending living kidney transplant programs in communities with widespread transmission to avoid exposing recipients to increased risk of immunosuppression, while recommendations were made to reserve deceased-donor kidney transplantation for likely life-saving indications. SOT recipients may be at high risk from COVID-19 disease due to chronic immunosuppressive treatment and other medical comorbidities. Mortality rates reported between 13 to over 30% in SOT recipients. In addition to high rates of complications and mortality attributable to COVID-19 infections, the pandemic has also led to additional complexities in transplantation including new questions regarding screening of donors and recipients, decision making to accept a patient for kidney transplant or wait after pandemic. The clinical implications of COVID-19 infection may also differ depending on the type of the transplanted organ and recipient comorbidities which further impacts decisions on continuing transplantation during the pandemic. Transplant activity during a pandemic should be tailored with careful selection of both donors and recipients. Furthermore, while tremendous strides have been made in treatment strategies and vaccinations, the impact of these in transplant recipients may be attenuated in the setting of their immunosuppression. In this review, we aim to summarize several aspects of COVID-19 in transplantation, including the immune response to SARS-CoV-2, SARS-CoV-2 diagnostics, clinical outcomes in SOT recipients, and end-stage kidney disease patients, transplant activity during the pandemic, and treatment options for COVID-19 disease.

We observed bacterial or fungal coinfections in COVID-19 patients admitted between March 1 and April 18, 2020 (152 of 4,267, 3.6%). Among these patients, mortality was 57%; 74% were intubated; 51% with bacteremia had central venous catheters. Time to culture positivity was 6–7 days, and 79% had received prior antibiotics. Metallo-β-lactamase–producing E. cloacae coinfections occurred in 5 patients.

PURPOSE:Inappropriate vancomycin for febrile neutropenia (FN) is an ideal antimicrobial stewardship target. To improve vancomycin prescribing, we instituted a multifaceted intervention, including an educational guideline with audit for compliance; an antibiotic use audit; and an assessment of local burden of methicillin-resistant Staphylococcus aureus (MRSA) colonization and infection.MATERIALS AND METHODS:We conducted a quasi-experimental pre-post intervention review of vancomycin initiation for FN on a 32-bed hematology/oncology unit. A retrospective chart review was conducted from November 2015 to May 2016 (preintervention period). In January 2017, we implemented an institutional FN guideline emphasizing criteria for appropriate use. Vancomycin audit was conducted from February 2017 to October 2017 (postintervention period). The primary outcome was appropriateness of vancomycin initiation. We then compared average antibiotic use (days of therapy per 1,000 patient days) for vancomycin and cefepime before and after intervention. Finally, unit-wide MRSA screening cultures were obtained upon admission and bimonthly for 6 weeks (October 2, 2017, to November 9, 2017). Screened patients were followed for 12 months for clinical MRSA infection.RESULTS:Forty-three (49%) of 88 preintervention patients were started on empiric vancomycin appropriately, compared with 59 (66%) of 90 postintervention patients ( P = .02). There was a significant decrease in vancomycin use after intervention. Six (7.1%) of 85 patients screened positive for MRSA colonization. During the 12-month follow-up, no colonized patients developed clinical MRSA infections (positive predictive value, 0.0%). Of the 79 noncolonized patients, 2 developed a clinically significant infection (negative predictive value, 97.5%).CONCLUSION:Guideline-focused education can improve vancomycin appropriateness in FN and should be bundled with education and feedback about local MRSA epidemiology and antibiotic use rates for maximal stewardship impact.

The widespread use of facemasks has been a crucial element in the control of the SARS‐CoV‐2 pandemic. With mounting evidence for mask efficacy against respiratory infectious diseases and greater acceptability of this intervention, it is proposed that masking should continue after the pandemic has abated to protect some of our most vulnerable patients, recipients of stem cell and solid organ transplants. This may involve not only masking these high‐risk patients, but possibly their close contacts and the healthcare workers involved in their care. We review the evidence for mask efficacy in prevention of respiratory viruses other than SARS‐CoV‐2 and address the burden of disease in transplant recipients. Although we acknowledge that there are limited data on masking to prevent infection in transplant recipients, we propose a framework for the study and implementation of routine masking as a part of infection prevention interventions after transplantation.

Kidney-Transplant Recipients with Covid-19 A cohort of 36 consecutive kidney-transplant recipients had less fever, lower CD3, CD4, and CD8 cell counts, more rapid clinical deterioration, and a high...

Lung transplantation is a lifesaving intervention for patients with advanced lung disease. Due to a combination of immunosuppression, continuous exposure of the lungs to the environment, and complications at the anastomotic sites, lung transplant recipients are at high risk for infectious complications. The aim of this review is to summarize recent developments in the field of infectious diseases as it pertains to lung transplant recipients.

Objectives To use a standardized tool for a multicenter assessment of antibiotic appropriateness in ICUs and identify local antibiotic stewardship improvement opportunities. Design Pilot point prevalence conducted on October 5, 2016; point prevalence survey conducted on March 1, 2017. Setting ICUs in 12 U.S. acute care hospitals with median bed size 563. Patients Receiving antibiotics on participating units on March 1, 2017. Interventions The Centers for Disease Control and Prevention tool for the Assessment of Appropriateness of Inpatient Antibiotics was made actionable by an expert antibiotic stewardship panel and implemented across hospitals. Data were collected by antibiotic stewardship program personnel at each hospital, deidentified and submitted in aggregate for benchmarking. hospital personnel identified most salient reasons for inappropriate use by category and agent. Measurements and main results Forty-seven ICUs participated. Most hospitals (83%) identified as teaching with median licensed ICU beds of 70. On March 1, 2017, 362 (54%) of 667 ICU patients were on antibiotics (range, 8-81 patients); of these, 112 (31%) were identified as inappropriate and administered greater than 72 hours among all 12 hospitals (range, 9-82%). Prophylactic antibiotic regimens and PICU patients demonstrated a statistically significant risk ratio of 1.76 and 1.90 for inappropriate treatment, respectively. Reasons for inappropriate use included unnecessarily broad spectrum (29%), no infection or nonbacterial syndrome (22%), and duration longer than necessary (21%). Of patients on inappropriate antibiotic therapy in surgical ICUs, a statistically significant risk ratio of 2.59 was calculated for noninfectious or nonbacterial reasons for inappropriate therapy. Conclusions In this multicenter point prevalence study, 31% of ICU antibiotic regimens were inappropriate; prophylactic regimens were often inappropriate across different ICU types, particularly in surgical ICUs. Engaging intensivists in antibiotic stewardship program efforts is crucial to sustain the efficacy of antibiotics and quality of infectious diseases care in critical care settings. This study underscores the value of standardized assessment tools and benchmarking to be shared with local leaders for targeted antibiotic stewardship program interventions.

Inappropriate vancomycin for febrile neutropenia (FN) is an ideal antimicrobial stewardship target. To improve vancomycin prescribing, we instituted a multifaceted intervention, including an educational guideline with audit for compliance; an antibiotic use audit; and an assessment of local burden of methicillin-resistantWe conducted a quasi-experimental pre-post intervention review of vancomycin initiation for FN on a 32-bed hematology/oncology unit. A retrospective chart review was conducted from November 2015 to May 2016 (preintervention period). In January 2017, we implemented an institutional FN guideline emphasizing criteria for appropriate use. Vancomycin audit was conducted from February 2017 to October 2017 (postintervention period). The primary outcome was appropriateness of vancomycin initiation. We then compared average antibiotic use (days of therapy per 1,000 patient days) for vancomycin and cefepime before and after intervention. Finally, unit-wide MRSA screening cultures were obtained upon admission and bimonthly for 6 weeks (October 2, 2017, to November 9, 2017). Screened patients were followed for 12 months for clinical MRSA infection.Forty-three (49%) of 88 preintervention patients were started on empiric vancomycin appropriately, compared with 59 (66%) of 90 postintervention patients (Guideline-focused education can improve vancomycin appropriateness in FN and should be bundled with education and feedback about local MRSA epidemiology and antibiotic use rates for maximal stewardship impact.

Background In February 2019, the American Society of Transplantation (AST) published guidelines on the management of asymptomatic bacteriuria (AB) and urinary tract infections (UTIs) in kidney transplant (KT) recipients. These recommendations include avoiding treatment of AB > 2 months post-transplant and outline the duration of treatment (DT) for uncomplicated and complicated UTIs. We reviewed management of these syndromes and guideline concordance at our institution. Methods We conducted a single-center, retrospective cohort study of KT recipients age > 18 years who underwent transplantation between June 2016 - June 2020. Patients were obtained through query of our electronic medical record for documented UTI syndromes and included if a diagnosis was confirmed between March 2019 - December 2020 upon chart review. Definitions of AB, complicated UTI, and uncomplicated UTI were based on AST definitions. Patients with AB < 2 months post-transplant were excluded. Outcomes included treatment of AB, DT, 30-day hospital admission and re-admission, and 30-day mortality. Bivariate analysis was conducted using chi square and t test. Results Seventy-four patients (mean age 55.4 years, 62.0% female) were included. Twenty-one patients had AB, 90% of whom received antibiotics. Distribution of diagnoses and median DT among those treated with antibiotics is outlined in Table 1. Overall DT was similar in patients whose care included infectious disease (ID) input and those who did not (10.0 vs. 10.0 days, p=0.12), although ID involvement was more common in complicated UTIs. There was no difference in 30-day admission rates for those receiving < 7 days vs. > 7 days of antibiotics (p=0.53) (Table 2) including those with complicated UTIs (5/15 in < 7 days (33%) vs. 4/18 in > 7 days (22%) p=0.49). There were no deaths within 30 days of diagnoses. Conclusion Despite guidelines, treatment of AB is common and uncomplicated UTIs often receive prolonged courses of antibiotics. There was no increased risk of admission or mortality with shorter DT, though these results should be interpreted cautiously given the small sample size. Greater stewardship efforts are needed in this high-risk population. Disclosures Kelsie Cowman, MPH, Merck (Research Grant or Support)

Fungal periprosthetic joint infections due to Aspergillus species are rare but are associated with significant cost and morbidity. We present a case of Asperigillus terreus prosthetic joint infection of the hip. The patient was successfully treated with a prolonged course of systemic antifungals along with surgical management. Keywords: Fungal prosthetic joint infection, Aspergillus terreus

Purpose Delay or complete lack of integration with the HeartMate 3 (HM3) driveline has led to an increased incidence of driveline infection (DLI). Negative pressure wound therapy (NPWT) may be helpful in decreasing the rate of infection by facilitating integration, therefore we evaluated the possible benefits of a single use NPWT system (Prevena) on DLI outcomes (Figure 1). Methods Retrospective chart review of primary HM3 patients implanted from January 2019 through October 2020. The INTERMACS 2016 definition of DLI was utilized. DLI outcomes were analyzed using Fisher's exact test. Freedom from DLI for the NPWT and non NPWT groups were analyzed using the Kaplan-Meier method. Results Within the study period there was a total of 40 primary implants. Twenty- two patients were implanted between January 2019 and October 2019 (non NPWT group) and 18 patients were implanted between November 2019 and October 2020 (NPWT group). In the non NPWT group, 3 patients developed DLI in the first six months (14 %). In the NPWT group, 1 patient developed DLI in the first six months (6 %) (p = 0.512, Figure 2).Average length of time to infection in the NPWT group was 146 days vs 69.3 days in the non NPWT group. Although exit site diameter tended to be smaller with the NPWT approach, overall integration and mobility of the driveline in its transcutaneous track was similar. Conclusion In a moderate size single center experience, use of a NPWT approach led to a decrease in DLI rate. Larger studies are needed to validate this finding.

BACKGROUND: Adoptive immunotherapy using CD19-targeted Chimeric antigen receptor T cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). Data is limited on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. METHODS: We conducted a retrospective study including 19 patients who received axicabtagene ciloleucel and investigated associations between cytopenia and infectious complications after D30. RESULTS: Nineteen patients were included, consisting of 42% Hispanic, 32% Caucasian, 21% African-American, and 5% Asian subjects. Post-D30 of CAR-T infusion, 47% patients (n=9) developed an infection and 53% (n=10) remained infection-free. The most common infection type observed was viral (7 patients) followed by bacterial (5 patients) and fungal (3 patients). Of 25 total infectious events, 56% were grade 1 or 2 and 44% were grade 3 with 10 being viral in etiology. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median absolute lymphocyte count (ALC) (1,000/µL vs. 600/µL, P1,500/µL in the infection group as opposed to 70% in the non-infection group at D90 (P

Background: Left-ventricular-assist device (LVAD)–related infections occur in 20%–40% of LVAD recipients and may result in up to 10% of LVAD-related deaths. Optimal surgical infection prophylaxis for LVAD implantation is not well defined. Our institution historically used a 4-drug surgical infection prophylaxis regimen of fluconazole, ciprofloxacin, rifampin, and vancomycin as recommended by the device manufacturer. In January 2020, a 2-drug surgical infection prophylaxis regimen of vancomycin and cefazolin was implemented to reduce broad-spectrum antibiotic use while preserving gram-positive coverage. The primary objective of this study was to compare LVAD-associated infection rates before and after changing surgical infection prophylaxis. Methods: A retrospective review of patients who underwent LVAD implantation between January 2018 and January 1, 2021, was performed. Definitions of LVAD-associated infections and non-LVAD infections were based on the International Society for Heart and Lung Transplantation guidelines. Infection rates at 2 weeks and 30 days after implantation and 30-day mortality were compared between the 4-drug surgical infection prophylaxis regimen (January 2018–December 2019) and the 2-drug regimen (January 2020–January 2021). Additional data collected included demographics, cause of cardiomyopathy, type of infection, and causative organism. Results: In total, 51 patients were in the 4-drug surgical infection prophylaxis group and 23 patients were in the 2-drug surgical infection prophylaxis group. Baseline characteristics between the groups were similar. The cause of cardiomyopathy in both groups was predominantly nonischemic (67% vs 70%, = .81), and most patients received a Heartmate III device (84% vs 100%, P = .06). There was no statistical difference between infection rates in the 4-drug and 2-drug prophylaxis groups at 2 weeks or 30 days (Table 1). The 30-day mortality rate was 4% in the 4-drug group versus 13% in the 2-drug group (P = .17). No deaths were due to infections. Gram-negative and fungal LVAD–associated infections were rare: 4% versus 4% (P = .99) for gram-negative infections and 2% versus 0% (P = .99) for fungal infections. The most commonly isolated organisms were Staphylococcus aureus and coagulase-negative Staphylococcus in both groups. Pneumonia was the most common infection in both groups (Figure 1). Conclusions: We did not observe a significant increase in infection or mortality with narrowing of perioperative antibiotics. However, these results should be interpreted cautiously given the small sample size. Larger studies are needed to confirm these findings.Funding: NoDisclosures: None

Staphylococcal bacteremia and enterococcal bacteremia are prevalent in hospitalized or recently instrumented patients, and are associated with significant morbidity and mortality. They are often difficult to treat due to the pathogenicity of the organisms, poor response to antibiotics, and increasing development of multidrug resistance. Therefore, there has been increasing interest in combination therapy for the treatment of these infections. The aim of this review was to summarize and assess the evidence supporting combination beta-lactam therapy for both Staphylococcus aureus and Enterococcus species blood stream infections. Currently, there is promising in vitro data but little clinical evidence supporting combination beta-lactam therapy for this indication. Further clinical investigations are needed to elucidate the potential benefits of beta-lactam combination therapy over monotherapy for Gram-positive bacteremia, although combination therapy may be useful in refractory cases of bacteremia that do not respond to standard antibiotic therapy.

Background: Adoptive immunotherapy using CD19-targeted Chimeric Antigen Receptor T-cells (CAR-T) has revolutionized the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL). We have demonstrated the efficacy of FDA-approved axicabtagene ciloleucel (Yescarta) in a multiethnic New York City underserved population with 80% complete response (CR) rate in the first ten patients treated at our institution (Abbasi et al., 2020). There is limited data on the propensity of infections and lymphohematopoietic reconstitution after Day 30 (D30) following CAR-T cell therapy. In this study, we evaluated the prevalence and nature of infectious complications in an expanded cohort of DLBCL patients treated with CD19 CAR-T therapy and its association with the dynamics of leukocyte subpopulation reconstitution post-CAR-T cell therapy. Methods: We conducted a retrospective study of patients who received CAR-T therapy at our institution between 2018-2020. Variables collected include patient demographics, absolute neutrophil (ANC), lymphocyte (ALC) and monocyte counts (AMC) at Day 30, hematologic reconstitution (ANC≥ 1500/µL) at Day 90 (D90), presence or absence of infections after D30 by clinical and/or microbiological parameters. Associations between presence of infection and D30 ANC, ALC, AMC, ANC/ALC ratio, AMC/ALC ratio were assessed using Kruskal-Wallis test. Association between infection and hematologic reconstitution at D90 was done using Chi-square test. Kaplan-Meier curves with log-rank test were used to evaluate overall survival (OS) and progression-free survival (PFS). Results: Nineteen patients were evaluated in our study, consisting of 42% (8) Hispanic, 32% (6) Caucasian, 21% (4) African-American, and 5% (1) Asian subjects. Based on clinical and microbiologic data, 47% (9) developed an infection after D30 (infection group) while 53% (10) of subjects remained infection-free after D30 (non-infection group). The most common infection type observed was viral (11 patients) followed by bacterial (8 patients) and fungal (3 patients) (Table 1). Of 25 total infectious events, 44% (11) were grade 1 or 2 and 48% (12) were grade 3 with 10 being viral in etiology. Two deaths occurred due to an infectious process. Three patients tested SARS-CoV-2 positive and were hospitalized with COVID-19 pneumonia. Median OS and PFS has not been reached in either group. To determine the kinetics of lymphohematopoietic reconstitution and its association with infection risk, we evaluated the relationship between cytopenias and rates of infection after D30. Notably, compared to non-infection group, infection group had a higher median ALC (1000/µL vs 600/µL p=0.04), a lower median ANC/ALC ratio (1.4 vs 4.5 p1500/µL) at D90. We observed that only 22% (2) of patients had recovered ANC > 1500/µLin the infection group as opposed to 80% (8) in the non-infection group at D90 (p= 0.038). Rates of cytokine release syndrome (CRS) were comparable between the two groups (55.6% vs 70% p=0.52). Surprisingly, rates of immune-effector cell associated neurotoxicity syndrome (ICANS) was lower (55.6%) in the infection group compared to (90%) non-infection group (p=0.09). Fourteen of 19 patients had follow-up over one year, of which 8 (57%) remained in complete remission (CR). Conclusions: We demonstrate an infection rate of 47% (9) beyond D30 in patients undergoing CD19 CAR-T. Increased ALC, lower ANC/ALC and AMC/ALC ratios at D30 may be predictive of infectious complications. Median OS has not been reached in our cohort. Given the potential clinical impact, our observations should be corroborated using larger datasets. Disclosures Steidl: Pieris Pharmaceuticals: Consultancy; Bayer Healthcare: Research Funding; Stelexis Therapeutics: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Aileron Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Janakiram:ADC Therapeutics, FATE therapeutics, TAKEDA pharmaceuticals: Research Funding. Verma:BMS: Consultancy, Research Funding; acceleron: Consultancy, Honoraria; Janssen: Research Funding; stelexis: Current equity holder in private company; Medpacto: Research Funding.

Background Antibiograms are important stewardship tools for empiric antibiotic prescribing. Appropriate therapy is particularly important in patients with hematologic malignancies and bone marrow transplants being treated for febrile neutropenia. These patients are at high risk for multi-drug resistance based on extensive prior antibiotic and hospital exposures, and therefore, hospital-wide antibiograms may not reliably reflect resistance patterns for this population. We created a unit-specific antibiogram for a closed hematology/oncology unit and hypothesized there would be decreased antibiotic susceptibilities compared to the hospital-wide antibiogram. Methods All positive cultures with antimicrobial susceptibilities on a closed 32-bed hematology-oncology unit from 7/2016-6/2019 were obtained from the microbiology laboratory. Based on recommendations by the Clinical and Laboratory Standards Institute (CLSI), only organisms with > 30 isolates were included in antibiogram analysis. Susceptibilities were compared to those reported in our hospital-wide antibiograms from the same time period using Fisher’s exact test. Results Two organisms met CLSI criteria: Escherichia coli (n=83) and Klebsiella pneumoniae (n=31). Unit Escherichia coli isolates were significantly more resistant to almost all commonly tested antibiotics (Table 1). Klebsiella pneumoniae unit susceptibilities were significantly lower for many antibiotics, including aztreonam, ceftriaxone, cefepime, levofloxacin, piperacillin-tazobactam and tobramycin (Table 1). Table 1: Percentage of Escherichia coli and Klebsiella pneumoniae isolates susceptible to reported antibiotic agents Conclusion Our hematology-oncology antibiogram showed significantly lower antibiotic susceptibilities in Escherichia Coli and Klebsiella pneumoniae compared with the hospital-wide antibiogram. These findings can help guide prescribers toward appropriate broad-spectrum empiric therapy. Additionally, results suggest a need for intensified stewardship measures to prevent multi-drug resistance in this population. Disclosures All Authors: No reported disclosures

Background: New York City is a gateway for emerging pathogens and global threats. In 2013, faculty from Montefiore Medical Center and Memorial Sloan Kettering developed a free half-day workshop for postgraduate trainees in antimicrobial stewardship (AS), infection prevention (IP), hospital epidemiology, and public health. This annual workshop, sponsored by the Infectious Diseases Society of New York (IDSNY), incorporates case studies and expert panel discussions on timely topics such as Ebola, Candida auris, Clostridiodes difficile, measles, nosocomial influenza, drug shortages, and AS/IP “big data.” Methods: From 2013 through 2017, the workshop involved 10–15 interactive AS/IP cases with audience response questions and panel discussions. In 2018–2019, based on feedback, the format was revised to emphasize breakout sessions in which participants actively practiced AS/IP tools, (eg, medication utilization evaluations, epidemiologic curves, and performance improvement devices). Examples of 2018–2019 cases are shown in Figure 1. A pre- and postseminar paper survey was conducted yearly to understand baseline training in AS/IP, desire for future AS/IP careers, and self-reported effectiveness of the workshop. Results: Initially, the primary audience was NYC ID fellows. From 2018 onward, we opened enrollment to pharmacy residents. Approximately 45 NYC ID fellows were eligible for the course each year. Results from 2013 to 2016 surveys were reported previously (Fig. 2). There were 32 attendees in 2018, 42 in 2019. The survey response rate was 88% in 2018 and 95% in 2019, with 68 (92%) total participants. Most participants had received previous training in IP (82%) and AS (94%) (Fig. 3). Most participants reported that the program was a good supplement to their ID training (98%) and that case studies were an effective means of learning IP (100%) and AS (98%). Furthermore, 92% stated they would like additional AS/IP training, and many since 2013 have requested a full-day course. Self-reported interest in future involvement in AS/IP increased after the workshop: IP, 68%–83% (P =.04) and AS, 88%–91% (P = .61). Conclusions: Most trainees reported satisfaction with the workshop and case-study learning method; interest in future AS/IP careers increased after the seminar. We intend to explore Funding: to expand to a full-day program for all NYC postgraduate trainees and AS/IP junior faculty. As such, we hope to obtain the endorsement of professional societies such as SHEA. This workshop could address a crucial educational gap in AS/IP postgraduate training and help sustain our future workforce.Funding: NoneDisclosures: None

We engaged medical students with antimicrobial stewardship (AS) and resistance (AMR) through patient stories and a panel on AMR advocacy with experts from the Centers for Disease Control and Prevention and the Infectious Diseases Society of America. Students were surveyed on their perceptions about AS and AMR (response rate=139/166, 84%).

Burnout is pervasive in academic medicine. We administered the Maslach Burnout Inventory and an Infectious Diseases (ID) job description survey to our ID faculty. Respondents’ burnout (>50%) and job satisfaction (>90%) were each high. Although burnout may be balanced by job satisfaction, the relationship between the 2 deserves further study.

• Critically-ill COVID-19 patients with New Delhi Metallo-beta-lactamase producing Enterobacterales infections at our medical center had poor outcomes, including death in 4 of 5 cases • Multiple insults contributed to the occurrence of co-infection in these patients, including prolonged hospitalization, intubation, invasive devices, extensive antibiotic use, immunosuppressive therapy and environmental factors • There are few antibiotic options for treatment of infections with New Delhi Metallo-beta-lactamase producing Enterobacterales, contributing to poor outcomes • Hospitals and public health authorities should be vigilant for extensively drug resistant bacterial co-infections in patients hospitalized with COVID-19

Background Developing robust, multidisciplinary antimicrobial stewardship programs to combat drug resistance is a priority of healthcare institutions, in accordance with Joint Commission standards and national legislature. However, the involvement of nurses in stewardship programs has trailed behind that of physicians and pharmacists, despite their unique position as frontline providers. In particular, oncology nursing staff can play a key role in extending stewardship to their high acuity patients, who frequently require antimicrobials. We sought to conduct a survey study of oncology nursing providers on their understanding, perceptions, and attitudes about antimicrobial stewardship. Methods A voluntary and anonymous survey was emailed to oncology nursing staff on adult and pediatric oncology wards and clinics throughout our hospital system. We used an adapted 28-item Likert scale-based survey to assess understanding of antimicrobial stewardship attitudes and perceived barriers to greater involvement in stewardship programs. A survey reminder was emailed weekly for 8 weeks and completion was encouraged by nursing leadership in unit staff meetings. Results The survey was emailed to 281 nurses, of whom 39% (n=109) responded. 54.1% of nurses believed that an antibiotic stewardship program was very important in their healthcare setting. However, 56% of respondents were unfamiliar with the meaning of antibiotic stewardship, and 83.5% were not aware of how to contact the antimicrobial stewardship team with questions. More than 75% felt that nurses could help with antibiotic use, though 76% indicated wanting to know more about which antibiotics treat different infections and 74% wanted to know more about appropriate durations of antibiotics. Conclusion Oncology nurses have the potential to play a valuable role in antimicrobial stewardship. Barriers to nursing involvement include knowledge gaps on antibiotics and unfamiliarity with existing stewardship programs and their functions within hospital systems. Nursing education and orientation to available resources are key steps to involving nursing staff in antimicrobial stewardship programs, maximizing benefits for both patients and hospitals. Disclosures All Authors: No reported disclosures

Background A syndromic gastrointestinal pathogen panel (GIP) was implemented in May 2018. All positive (+) GIP and standard-of-care (SOC) C. difficile results were reviewed. Methods A single-center audit of adult patients with GIP results was conducted May–December 2018. We reviewed GIP(+)/SOC(+/-) and GIP(-)/SOC(-) tests (control group) for clinical outcomes. Results We reviewed 269 GIP(+) patients. Of 119 GIP(+)/SOC(+) patients, 44 (37%) were positive by toxin A/B enzyme immunoassay, and 75 (63%) by PCR only. Thirty-day mortality and re-admission were not significantly different between groups. CDI rates within 6 months were not significantly different between GIP(+)/SOC(-) and controls (p-value = 0.39). Those with initial SOC(+) tests had more true CDI events within 6 months, compared to controls (p-values Conclusions Forty percent of patients with GIP(+) C. difficile were (-) by SOC test, suggesting that true CDI was not present. Additional PCR-based testing may not impact outcomes.

Background The National Healthcare Safety Network (NHSN) provides risk-adjusted Standardized Antimicrobial Administration Ratios (SAAR) as a benchmark for medical and surgical intensive care units (ICU). Antibiotic use (AU) data does not provide patient-level information (e.g., antibiotic appropriateness, indications, durations, etc.). However, we hypothesize that AU data can help define high impact stewardship targets, particularly in the context of critical care Clostridioides difficile rates. Methods Units with high rates of AU and hospital-onset (HO) C. difficile were selected for review. A monthly AU and C. difficile dashboard was created for ICU providers, inclusive of data from May 2018 onwards. We also performed chart audits for indication, duration, and location of initiation for all medical intensive care unit (MICU) patients receiving piperacillin/tazobactam (P/T) or vancomycin (Van) during February 2019 per request of ICU stakeholders. Data were used to obtain stewardship buy-in from local MICU champions. Results AU data indicated that (1) all 3 MICUs consistently had SAARs >1 for broad-spectrum categories and (2) Van and P/T were the highest volume agents on these units (Figure 1). Chart audit of 135 MICU patients showed that 17 patients received P/T, 34 Van, and 84 (62%) both agents; median duration was 2 days for Van and 3 days for P/T (Figure 2). Approximately half of initiations occurred in the emergency department (ED) (50% Van, 47% P/T); most common indications were “respiratory tract infection” and “severe sepsis/septic shock” for both P/T (77%) and Van (74%) (Figure 2). HO C. difficile in MICUs accounted for 6%, 13%, and 16% of total HO C. difficile cases in campuses A, B, and C, respectively during the time frame (Figure 1). Conclusion We feel that NHSN data scratches the surface of the deep-rooted challenges of ICU stewardship. However, it can identify AU trends and most frequently prescribed antibiotics in the context of unit-specific C. difficile rates. Intensive stewardship audit can further uncover areas for intervention, such as ED Van and P/T overprescribing. We suggest presenting clinical stakeholders with a quarterly “stewardship dashboard” combining AU rates, patient-level data, and C. difficile rates to maximize the impact of stewardship endeavors. Disclosures All authors: No reported disclosures.

Background Inappropriate IV vancomycin prescribing for febrile neutropenia (FN) is an excellent stewardship target given well-established guidelines specifying indications for its use. As a supplement to an educational initiative with institutional FN guidelines, we conducted methicillin-resistant Staphylococcus aureus (MRSA) colonization screening to estimate its prevalence on our hematology/oncology unit. We hypothesize that MRSA prevalence data can augment existing stewardship efforts to improve IV vancomycin use in FN. Methods (1) Pre-intervention: we conducted a retrospective chart review of vancomycin receipt for FN on a 32-bed Hematology/Oncology unit, November 2015–May 2016 (control group). (2) Intervention: in January 2017, we implemented an institutional FN guideline with recurring education to hematology/oncology providers emphasizing criteria for appropriate vancomycin initiation. Vancomycin audit was again conducted from February 2017–October 2017 (intervention group). The primary outcome was appropriateness of vancomycin use per guideline indications (chi-squared analysis). Use was considered inappropriate if no guideline indications were met. (3) MRSA screening: cultures were obtained from the nares, axilla and groin on admission and bimonthly for 6 weeks and plated on CHROMagar. Screened patients were followed for 5 months for the occurrence of clinical MRSA infection. Results Forty-three of 88 controls were started on vancomycin appropriately vs. 60 of 91 intervention group patients (49% vs. 66%, P = 0.02). Results of MRSA screening and follow-up for invasive infection are shown in Table 1. Conclusion Recurring, guideline-focused education can improve appropriateness of vancomycin for FN. High NPV in our study supports the hypothesis that MRSA screening can augment stewardship efforts to reduce vancomycin use when not indicated. Disclosures All authors: No reported disclosures.

Background A national assessment of antibiotic appropriateness in intensive care units (ICUs) with benchmarking was performed to assist antibiotic stewardship programs (ASPs) identify improvement opportunities. Methods A Centers for Disease Control and Prevention tool was adapted by an expert panel from the Partnership for Quality Care (PQC), a coalition dedicated to high quality care in US hospitals, to validate appropriate antibiotic use measurement via a point prevalence survey on a single day. Data were collected by ASP personnel at each hospital, de-identified and submitted in aggregate to PQC for benchmarking. Hospitals identified reasons for inappropriate antibiotic use by category and antibiotics misused. Results Forty-seven ICUs from 12 PQC hospitals participated: California (2), Florida (2), Massachusetts (3), Minnesota (1), and New York (4). Most hospitals identified as teaching (83%) with 252-1550 bed size (median: 563) and 20–270 licensed ICU beds (median: 70). All hospitals reported a formal ASP. On March 1, 2017, 362 (54%) of 667 patients in participating ICUs were on antibiotics (range: 8-81 patients); 1 patient was not assessed. Of the remaining 361 antibiotic regimens, 112 (31%) were identified as inappropriate from among all 12 hospitals (range: 9-82%) (figure). The table displays inappropriate antibiotic use by ICU type. Reasons for inappropriate use included unnecessarily broad spectrum of activity (29%), duration longer than necessary (21%), and treatment of a non-infectious syndrome (19%). The antibiotic most commonly misused was vancomycin in 7 (58%) hospitals. Conclusion Up to 80% of antibiotic use in some ICUs is inappropriate, underscoring the need for ASP interventions, standardized assessment tools and benchmarking. Strategies should focus on de-escalation of broad-spectrum antibiotics and reducing duration of therapy. Disclosures D. W. Kubiak, Shionogi: Consultant, Consulting fee. Astellas Pharma: Consultant, Consulting fee