Background Monoclonal antibodies (mAbs) against SARS-CoV-2 are potent therapeutics that prevent progression of disease in high-risk patients. Deploying mAb infusion programs and reaching communities in need remains challenging. We established a mAb infusion program centered in the emergency department (ED) fast-track. We seek to assess the feasibility and impact of our mAb infusion program in reaching vulnerable underserved communities. Methods The ED fast-track was repurposed for mAb infusions. Indications and protocols were created by the infectious disease (ID) physician and antimicrobial stewardship program (ASP). Test to treat was deployed in the ED and a referral program connected patients from telehealth and providers in the community to the infusion program (Figure 1). Data on mAb use from November 2020 to February 2022 was reviewed. To assess the reach of the program in vulnerable communities, the COVID-19 Community Vulnerability Index (CCVI) map by zip code was used. The CCVI identifies communities at risk by using variables such as sociodemographic variables, occupational factors, cumulative COVID-19 burden, vaccine uptake and other factors. Figure 1.Monoclonal antibody infusion test-to-treat and referral process in the ED fast track Results mAbs were successfully deployed and sustained throughout the pandemic, increasing its use in each COVID-19 surge by >103% (Figure 2). A total of 267 patients were treated, with an average age of 52 years, of which 55% (147) were female. Ethnicity was 46% Hispanic and Race was 54% White, 28% Black, 1.4% Asian, 1.8% Multiracial and 14% Other. Zip codes by CCVI were 64% high, 18% medium, and 3% low CCVI index. 15% were outside of city limits without CCVI index (Figure 3). Figure 2.COVID-19 Community Vulnerability Index (CCVI) of patients who received monoclonal antibodies at our program Figure 3 Monoclonal antibody infusions by COVID-19 Community Vulnerability Index (CCVI) and Zip codes Conclusion A mAb infusion program with test to treat and referrals from the community was successfully deployed in an ED fast track. The ED space and staff can be leveraged for mAbs during surges amid clinic staffing challenges. The program adopted novel mAbs as new COVID-19 variants emerged. Uptake increased with each wave, likely reflecting awareness of mAbs and the infusion program by patients and providers in the community. The majority of patients served (82%) were of high and medium CCVI. Thus, this mAb infusion program led by ID and ASP successfully reached predominantly underserved vulnerable populations. Disclosures All Authors: No reported disclosures.
Multiple myeloma (MM) is a plasma B‐cell malignancy characterized by osteolytic bone lesions. MM cells secrete and express CCL3/MIP1α which upregulates osteoclastogenesis. Elevated CCL3 levels display a chemotactic ability on isolated osteoclast precursors. Increased levels of CCL3 in MM patients correlates with a greater disease burden, due to the increase of bone resorption, and is indicative of a worse prognosis when compared to MM patients exhibiting lower CCL3 levels. CCR1, a GPCR chemokine receptor, is endogenously expressed on MM cells, and can bind with CCL3. In a previous study, the RPMI8226 MM cell line, CCL3‐mediated CCR1 chemotaxis was inhibited in a dose‐dependent manner by six CCR1 antagonists (AZD4818, BX471, CCX354, CP481715, MLN3897, PS031291). In this study, we assessed the MM cell line U266 as well as a transfected cell line, U266_CCR1. While U266 cells express lower levels of CCR1 than RPMI8226, U266_CCR1 express higher levels of CCR1. Cells were treated with a serial dilution of the same six CCR1 antagonists and chemotaxis to either supernatant from osteoclast precursor RAW 264.7 cells or Fetal Bovine Serum (FBS) in which a multitude of growth factors and chemokines are present was examined. We hypothesized the six CCR1 antagonists would result in a dose‐dependent inhibition of chemotaxis similar to that seen with RPMI8226. Instead, we found only two of the compounds (AZD4818 and BX471) inhibited chemotaxis of the U266 and U266_CCR1 MM cell lines towards RAW 264.7 supernatant or FBS. For both AZD4818 and BX471 there were differences between the chemotactic response of the U266 and U266_CCR1 cell lines, with the U266_CCR1 cell line having a greater degree of inhibition, suggesting the inhibition is driven by CCR1.
Background The use of peripherally inserted central catheters (PICCs) has increased in the past decade. PICCs are central lines (CLs) commonly used for venous access. Midline catheters (MLs) can provide access when the need for a CL, such as vasopressors, is no longer present. MLs have a lower rate of BSI compared to PICCs and CLs, while providing dwell times comparable to PICCs. We established a project prioritizing ML use. Methods This is a quasi-experimental study in a 151-bed safety net community hospital. The pre-intervention period was January-December 2018 and post period was January 2019-December 2021. MLs were prioritized when new PICCs are requested without CL indications, such as total parenteral nutrition, hyperosmolar solutions and vasopressors. PICCs and CLs are transitioned to a ML once indications are no longer met and peripheral IVs are not feasible. Data on utilization and complications, such as deep venous thrombus (DVT) and BSIs, were reviewed and compared. Results A total of 63 peripherally inserted lines occurred prior to the intervention, of which 55 (87%) were PICC and 8 (13%) were ML (Figure 1). Post-intervention, 76 lines were placed the first year, of which 48 were ML (63%). This upward trend was sustained throughout the pandemic, with 116 lines in 2020 (80% ML) and 96 in 2021 (88% ML). No BSIs occurred during the pre-intervention and first post-intervention year. During the pandemic, 8 BSIs in MLs and 3 in PICCs occurred. The most common organism was Candida (Figure 2). The majority had COVID-19 (72%) and all (100%) BSIs were in the setting of shock. Case review demonstrated suspected secondary sources other than central venous catheters (CVCs). All BSIs with ML would have met NHSN criteria if CL present. No upper extremity DVTs were found. Conclusion A midline prioritization project was successfully implemented and sustained during the COVID-19 pandemic. The decline of PICC use from 87% to 12% suggests use for access without CL needs. High acuity during the pandemic led to BSIs that were likely secondary to shock and complications of COVID-19. All cases would have met NHSN criteria for CLABSI. The cost of a CLABSI is estimated at $48,108. Thus, this midline prioritization project may have led to CLABSI avoidance and an estimated cost savings of $384,864. Disclosures All Authors: No reported disclosures.
Background The COVID-19 pandemic has caused record breaking hospitalizations due to respiratory failure. A major challenge in the management of COVID-19 is the difficulty distinguishing COVID-19 from other causes of lower respiratory tract infections (LRTIs) that may require antimicrobial use (AU). Procalcitonin (PCT) has been used to differentiate viral from bacterial causes of LRTIs and clinicians have relied on PCT to use or withhold antimicrobials. However, the utility of PCT in the setting of COVID-19 remains unclear. We seek to define the role of PCT in patients admitted with COVID-19. Methods Retrospective cohort study of COVID-19 inpatients with PCT ordered at a 151-bed urban community hospital from March 2020-March 2022. Ranges of PCT were categorized as high ( >5 µg/L), medium (0.25-5 µg/L), and low (< 0.25 µg/L) risk of infection. Co-infection was defined as presence of clinical and microbiological evidence of infection in blood (BSI) or in sputum within 7 days of admission. Late infections were excluded Results Of a total 262 cases, 154 (58%) were low-risk, 43 (16%) medium-risk, and 63 (24%) high-risk (Figure 1). AU in the low-risk category was 29% (45), followed by 29% in the moderate and 36% in high-risk categories. 1 BSI caused by Klebsiella pneumoniae in the low-risk category and 1 LRTI caused by Streptococcus pneumoniae in the high-risk category were found, representing 0.6% and 1.5% of samples in those categories. Total documented infection was 0.7% for all cases. Figure 1.Procalcitonin levels and co-infections in patients admitted with COVID-19 pneumonia. Conclusion PCT has limited utility in COVID-19. Co-infection rates on admission are exceedingly rare, representing < 1% of our cohort. Only 2 documented infections were found, 1 of which was in the low-risk category. Thus, PCT was commonly elevated without documented infection. Though rare, a co-infection can occur without elevation of PCT. As described in the 2019 IDSA Community Acquired Pneumonia Guidelines, the use of PCT is of limited utility and may confound providers towards using or deferring antimicrobials inappropriately. This remains true in COVID-19. Antimicrobial stewardship programs should advise against its routine use. Disclosures All Authors: No reported disclosures.
Background Lower respiratory tract infections (LRTIs) from SARS-CoV-2 are difficult to distinguish from other viral or bacterial etiologies. This has led to increased antimicrobial use (AU) during the pandemic and concerns for concomitant rise in antimicrobial resistance (AMR). It is crucial for antimicrobial stewardship (ASP) to develop strategies to mitigate excess AU and curve AMR. We leveraged a syndrome-based ASP intervention targeting LRTIs and the use of anti-Pseudomonal beta lactams (APBL) during the COVID-19 pandemic. Methods We incorporated COVID-19 elements into a syndrome-based prospective audit and feedback (PAF) at an urban community hospital. Elements included EMR order sets (Figure 1) that discouraged routine AU for COVID-19 and PAF targeting LRTIs and COVID-19 therapies. Empiric selection discouraging APBL was incorporated during the first COVID-19 wave. Order sets and PAF were then modified to reflect novel COVID-19 therapeutics and AU was strongly discouraged in subsequent waves. Data on AU and AMR from 2018-2022 was reviewed. Figure 1.Electronic medical records COVID-19 antimicrobial order set Results Average quarterly AU increased during the first pandemic year by 8.7%, from 359.5 to 391 days of therapy per 1000 patient days (DOT/1000), with peaks 22.5% above the pre-pandemic average during COVID-19 surges. AU increased each COVID-19 surge, with smaller peaks each subsequent wave. DOT/1000 declined 29% from the first wave to the Omicron wave. AU decreased the second year to 318, an 18.6% decrease from the first pandemic year. Ceftriaxone use increased during surges, reflecting our LRTI guidelines (Figure 2). Peaks declined each subsequent wave, from a peak of 239 in the first wave to 75 during Omicron, a 68% decrease. The average monthly DOT/1000 for APBL decreased from 73.51 to 63.21 (Figure 3). Incidence rate of ESBL and CRE initially rose and then declined (Figure 4). Figure 2.Antimicrobial use (DOT/1000) before and during the COVID-19 pandemicFigure 4.Antipseudomonal beta lactam use before and during the COVID-19 pandemic Figure 5. Incidence of multidrug resistance organisms before and during the COVID-19 pandemic Conclusion ASP successfully incorporated COVID-19 elements and steered AU during the pandemic. Though total AU increased, APBL use declined and AU peaks decreased with each COVID-19 wave, reflecting adherence with ASP recommendations. AMR increased during the first year and subsequently declined. ASP can play a vital role guiding AU during respiratory pandemics. Disclosures All Authors: No reported disclosures.
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