bluuebunny/crossref_metadata_2025 huggingface dataset:
LB8. Lower SARS-CoV-2 IgG and Pseudovirus Neutralization Titers Post-mRNA Vaccination among People Living with HIV
Authors: Spinelli Matthew A , Peluso Michael J , Lynch Kara , Yun Cassandra , Glidden David V , Henrich Timothy J , Deeks Steve , Gandhi Monica
Published: December 2021

Background

Limited data are available on whether there are differences in the immune response to SARS-CoV-2 vaccination by HIV status or by mRNA vaccine type.

Methods

We saved residual outpatient laboratory samples of all previously mRNA-vaccinated individuals in the adult medicine clinics of a public hospital with a large outpatient HIV clinic during May 2021, and then excluded individuals with prior SARS-CoV-2 infection. We next 1:1 matched 100 PLWH to 100 outpatient HIV-negative adult medicine patients receiving care for chronic medical conditions on days since completion of second vaccination (minimum 10), sex, age +/-5 years, and the type of mRNA vaccine received. We defined a non-response as reciprocal pseudovirus neutralizing titer< 10 and anti-RBD IgG< 10 relative fluorescent units, and compared non-response by HIV status using mixed models.

Results

In each matched group there were 13 women; 25 received the mRNA-1273 vaccine and 75 received the BNT162b2 vaccine; the median age was 59. The median time from second vaccination was 35 days (IQR: 20–63). Among PLWH, the median CD4+ T-cell count was 511 (IQR: 351–796) and 5 individuals had HIV RNA > 200.

We found 2.4-fold greater odds of pseudovirus neutralizing antibody non-response among PLWH compared to people without HIV (95% CI=1.1–5.4). Although few individuals in each group did not mount an IgG response (12 among PLWH vs. 5; p=0.08), continuous anti-RBD IgG concentrations were 43% lower among PLWH (95% CI=0.36–0.88).

Among PLWH, when adjusting for age, sex, and days post-vaccination, each 100-cell increase in CD4+T-cell count was associated with 22% higher neutralizing antibody titers (GMR 1.22; 95% CI=1.09–1.37). Unsuppressed HIV RNA >200 was associated with 89% lower neutralizing antibody titers (GMR 0.11; 95% CI=0.01–0.84). Receipt of the BNT162b2 vs. mRNA-1273 vaccine was associated with 77% lower neutralizing titers (GMR 0.23; 95% CI=0.08–0.65) among PLWH.

Post-mRNA Vaccination SARS-CoV-2 IgG Concentrations and Pseudovirus Neutralizing Titers by HIV Status and Vaccine

Conclusion

PLWH had lower than expected response to mRNA SARS-CoV-2 vaccines, with the highest non-response among those with low CD4+ counts, unsuppressed HIV RNA, and those who received the BNT162b2 vaccine. Immunization strategies to improve immune responses among PLWH should be studied, and may include booster vaccination or preference of the mRNA-1273 vaccine in this group.

Disclosures

Matthew A. Spinelli, MD, MAS, Nothing to disclose Monica Gandhi, MD, MPH, Nothing to disclose
LB9. Longitudinal antibody dynamics in children infected with SARS-CoV-2 through 6 months post-infection
Authors: Gentles Lauren E , Kehoe Leanne P , Crawford Katharine D , Lacombe Kirsten , Dickerson Jane , Yuan Joanna H , Schuler Susanna L , Nyanseor Sankan , Saydah Sharon , Midgley Claire , Pringle Kimberly , Bloom Jesse , Englund Janet A
Published: December 2021

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection elicits antibodies (Abs) that bind several viral proteins such as the spike entry protein and the abundant nucleocapsid (N) protein. We examined convalescent sera collected through 6 months (~24wks) post-SARS-CoV-2 infection in children to evaluate changes in neutralization potency and N-binding.

Methods

Outpatient, hospitalized, and community recruited volunteers < 18 years with COVID-19 were enrolled in a longitudinal study at Seattle Children’s Hospital. Analysis includes symptomatic and asymptomatic children with laboratory-confirmed SARS-CoV-2 infection who provided blood samples at approximately 4wks (range: 2-18wks, IQR:4-8wks) and 24 wks (range: 23-35wks, IQR:25-27wks) after diagnosis. We measured neutralizing Ab using an in-house pseudoneutralization assay and anti-N binding Ab using the Abbott Architect assay.

Results

Of 32 children enrolled between April 2020 and January 2021, 27 had no underlying immunocompromised state and 25 of these 27 children had symptomatic disease. Ten of 27 had a > 2-fold decrease neutralization titers between 4 and 24wks (most were < 10-fold); 12 had < 2-fold change; and 5 had neutralization titers that increased > 2-fold over time (Fig. 1A). All but one of these 27 children had detectable neutralizing activity at 24wks. Anti-N Abs were assessed for 25 children at 4wks and 17 children at 24wks (data pending for 14 samples); all children with paired samples had a > 1.75-fold Abbott index reduction at 24wks, and 5 children had no detectable anti-N Abs by 24wks (Fig. 2A). An additional 5 children with symptomatic disease had complicating immunosuppression or multiple blood transfusions; 2 had decreasing neutralizing titers, 2 increased, and 1 had no change (Fig. 1B). Anti-N Abs were undetectable for one child by 24wks (data pending for 4 samples) (Fig. 2B). No participants received COVID-19 vaccine.

Figure 1. Pseusoneutralization titers in children over time.

Figure 2. Nucleocapsid-binding antibody titers in children over time.

Conclusion

We show neutralizing Abs wane to a small degree over 24wks post-SARS-CoV-2 infection and remain detectable in most children. In contrast, anti-N Abs decreased, becoming undetectable in some children by 24wks. These findings add to understanding of the natural history of SARS-CoV-2 immunity in children.

* This study was supported by CDC BAA75D301-20-R-67897

Disclosures

Jesse Bloom, PhD, Flagship Labs 77 (Consultant)Moderna (Consultant) Janet A. Englund, MD, AstraZeneca (Consultant, Grant/Research Support)GlaxoSmithKline (Research Grant or Support)Meissa Vaccines (Consultant)Pfizer (Research Grant or Support)Sanofi Pasteur (Consultant)Teva Pharmaceuticals (Consultant)
166. Congenital Syphilis in Minnesota, 2016-2020
Authors: Lehnertz Nicholas , Bo-Subait Khalid , Hadsall Candy , Barber Cheryl , LaPointe Allison , Livingston Cindy Lind , Dippmann Karmen , Babcock Marcie , Kendrick Brian , Griffith Jayne , Liverseed Gina , Darrett-Brewer Peggy , Jones Christine L
Published: December 2021

Background

Nationally, cases of congenital syphilis (CS) have increased over the past 5 years. We reviewed CS cases in Minnesota from 2016-2020.

Methods

All cases of syphilis, including CS, are reported to the Minnesota Department of Health (MDH), including accompanying data on maternal age, baby’s sex, race, test results, maternal stage and treatment of mother and child. Medical records and case interviews were reviewed; the 2018 national case definition was used to classify cases.

Results

During 2016-2020, there were 47 CS cases from 45 mothers, peaking in 2020 at a rate of 3.2/10,000 live births. 43 (91.5%) cases of CS had no clinical signs, 1 (2.1%) CS case was inadequately treated, and there were 2 deaths.

The median maternal age was 28 (IQR 9, range 18-38). 13 (28.9%) identified as Black, non-Hispanic, 13 (28.9%) as American Indian/Alaska Native (AI/AN), 9 (20.0%) as White, non-Hispanic, 3 (6.7%) as Hispanic, 2 (4.4%) as Asian/Pacific Islander, and 5 (11.1%) Other/Unknown. Twenty-four (51.1%) cases occurred in the Minneapolis/St. Paul metropolitan area. 2 (4.4%) cases were primary, 1 (2.2%) was secondary, while 18 (40.0%) maternal cases were staged as early non-primary, non-secondary (ENPNS) and 24 (53.3%) were late unknown duration. 14 (31.1%) of mothers had their initial prenatal visit in the first trimester, 6 (13.3%) in the 2nd trimester, 11 (24.4%) in the 3rd, and 14 (31.1%) unknown. None of the maternal cases were HIV+, 2 were identified as positive for hepatitis C. 18 (40.0%) mothers had no or limited prenatal care, 21 (46.7%) had inadequate treatment for syphilis, and 18 (40.0%) had inadequate maternal testing. No cases reported substance use, but one case had a positive substance screen at delivery, and case interviews also documented a role of substance use and home instability in several other cases.

Conclusion

Case rates of CS are the highest ever seen in MN. There is disproportionate impact in persons of color and indigenous Minnesotans. Lack of access to prenatal care, missed opportunities for testing, and incomplete or insufficient treatment were found in maternal cases. More work needs to be done with communities at risk and with prenatal care providers to ensure adequate testing, identification and treatment for syphilis in women of child-bearing age.

Disclosures

All Authors: No reported disclosures
168. Testing, Diagnosis, and Incidence of Sexually Transmitted Infections Among People with Substance Use Disorders in the Veterans Health Administration, 2019
Authors: Villamagna Holly , Beste Lauren , Borgerding Joleen , Lowy Elliott , Hauser Ronald , Maier Marissa
Published: December 2021

Background

People with substance use disorders (SUDs) are at increased risk of acquiring sexually transmitted infections (STIs.) In response to the syndemic of STIs and SUDs, the Department of Health and Human Services’ 2020 STI National Strategic Plan called for increased STI testing among people with SUDs and integration of testing and treatment into non-traditional settings. Existing data describing STI testing and incidence rates among people with SUDs are limited to single or regional medical centers. National samples are needed to target interventions. We report on STI testing, test positivity, and incidence rates among people with SUDs who receive medical care in the Veterans Health Administration (VHA).

Methods

We performed a retrospective cohort study of individuals with SUDs who received VHA care in 2018 or 2019. Data were obtained from the Corporate Data Warehouse, a national database that includes data from VHA’s electronic medical record. For individuals with alcohol, opioid, cocaine, and/or other stimulant (e.g. methamphetamine) use disorders, we collected demographic data, testing and results for gonorrhea (GC), chlamydia (CT), syphilis, and HIV during 2019. We calculated rates of testing, test positivity, and incidence rates.

Results

Incidence of all four STIs was highest in the other stimulant use disorder group; incidence of syphilis was particularly elevated at 922.4 cases/100K. Veterans with multiple SUDs were three times more likely to be houseless in 2019 than those with a single SUD and had higher incidence of all STIs than those with single SUDs, except for people with other stimulant use disorders. People with alcohol use disorder (AUD) had a higher incidence of GC, CT, and syphilis than those with opioid use disorder despite similar testing rates. Percent positivity for HIV ranged from 0.27% for AUD to 2.0% for other stimulant use disorders.

Conclusion

High incidence of STIs among people with non-cocaine stimulant use disorder indicates a need for comprehensive testing. The data suggests that veterans with AUD would benefit from increased testing. Houselessness and mental health diagnoses were common, and comprehensive STI testing and treatment programs, including an assessment of HIV risk, should be integrated into programs addressing these comorbidities.

Disclosures

Holly Villamagna, MD, Nothing to disclose
198. Comparison of Antibiotic Treatment Durations for Symptomatic Bacteriuria in Veterans with Spinal Cord Injuries or Disorders (SCI/D)
Authors: Fang Michelle , Johns Scott T , Ma Ariel
Published: December 2021

Background

It is unclear based on published literature whether shorter courses of antibiotic treatment may be appropriate for urinary tract infections (UTI) in patients with SCI/D given their complex baseline clinical status.

Methods

This retrospective cohort study was conducted at the VA San Diego Healthcare System (VASDHS), which has a dedicated SCI/D unit. Adults with SCI/D were identified for inclusion if they had received antibiotics for a positive urine culture in conjunction with UTI symptoms from 1/2018-12/2020. Individual UTI events were excluded if associated with potential sources of harbored infection, anatomic abnormalities increasing risk of bacteriuria, non-bacterial pathogens, concurrent infections prolonging antibiotic treatment, or antibiotic courses managed outside of VASDHS. Treatment groups comprised UTI events treated with no more than 7 days of antibiotics (group 1) versus more than 7 days (group 2). Study endpoints were recurrence or new incidence of UTI within 30 and 90 days after completion of antibiotic treatment and onset of C. difficile infection or death within 30 or 90 days, respectively, after treatment completion. Statistical tests included Chi-square, Mann-Whitney U, and logistic regression.

Results

One-hundred and seven patients with 241 unique UTI events were included in this study, with 79 events in group 1 and 162 events in group 2. Baseline characteristics were similar across both groups, aside from a higher incidence of hospital admission and more severe SCI/D based on the American Spinal Cord Injury Association (ASIA) impairment scale in group 2. Efficacy outcomes are described in Table 1. No deaths occurred within 90 days of treatment completion, and C. difficile infection occurred in 1 patient in group 2 after 3 days of antibiotic therapy. Duration of antibiotic therapy was not predictive of treatment failure within 30 days of antibiotic completion. Factors predictive of treatment with longer courses of antibiotic therapy included hospital admission and more severe ASIA impairment scale score.

Table 1. Incidence of UTI after antibiotic completion

Conclusion

The findings of this study suggest that for some patients with SCI/D, UTI treatment lasting 7 days or fewer may be effective compared to longer courses of antibiotics and could be beneficial in reducing collateral damage from antibiotic use.

Disclosures

All Authors: No reported disclosures
01. Serum Bactericidal Activity Against Circulating and Reference Strains of Meningococcal Serogroup B in the United States: A Review of Meningococcal Serogroup B (MenB) Vaccines in Adolescents and Young Adults
Authors: Coyne-Beasley Tamera , Bocchini Joseph , Cane Alejandro , Burman Cindy , Tort Maria J , Presa Jessica
Published: December 2021

Background

US adolescents and young adults are at particular risk of invasive meningococcal disease (IMD). In 2018, menincococcal serogroup B was responsible for 36% of IMD cases in the US overall and for 66% of cases in adolescents and young adults. This age group is at high risk of IMD during outbreaks, which result in significant response-related costs. MenB vaccine efficacy against IMD relies on its ability to provide broad protection against diverse disease-causing strains. MenB-FHbp (Trumenba) and MenB-4C (Bexsero) are MenB vaccines licensed in the US as 2-dose series with an interval of 6 mo or 1 mo, respectively, recommended in healthy adolescents and young adults. We review available data on vaccine coverage of serogroup B strains.

Methods

A literature review identified relevant information from peer-reviewed publications, congress presentations, and ClinicalTrials.gov. Previously presented but unpublished data from phase 2/3 studies were included.

Results

After 2 MenB-FHbp doses, percentages of adolescents and young adults achieving serum bactericidal activity assay using human complement (hSBA) titers ≥1:8 were 79%–99% for 4 heterologous representative test strains and 71%–97% for 10 additional strains, confirming cross-protection against a diverse strain panel (Figure 1; unpublished data). These 14 heterologous strains collectively represent ~80% of disease-causing strains in the US and Europe. In a published study with limited sample size, 44%–78% of subjects had hSBA titers ≥1:8 against strains from 4 US college outbreaks after 2 MenB-FHbp doses. After 2 MenB-4C doses, percentages of 10–25-year-olds achieving hSBA titers ≥1:5 against 3 reference strains homologous to the vaccine antigen were 82%–93% (published data); 15%–100% of adolescents achieved hSBA titers ≥1:4 against a panel of 14 strains (unpublished data). Of college students who received 2 MenB-4C doses, 53%–93% achieved hSBA titers ≥1:4 against 5 US outbreak strains (4/5 strains had antigenic similarity to MenB-4C; published data).

Conclusion

MenB-FHbp and MenB-4C protect against various serogroup B strains. As for the breadth of coverage provided by these vaccines, available data show that MenB-FHbp elicits robust immune responses to a wide variety of disease-causing strains prevalent in the US (Figure 2).

Disclosures

Tamera Coyne-Beasley, MD, MPH, Pfizer Inc and GlaxoSmithKline (Advisor or Review Panel member) Joseph Bocchini, MD, Pfizer Inc and Dynavax (Advisor or Review Panel member) Alejandro Cane, M.D., Pfizer Inc (Employee, Shareholder) Cindy Burman, PharmD, Pfizer Inc (Employee, Shareholder) Maria J. Tort, PhD, Pfizer Inc (Employee, Shareholder) Jessica Presa, MD, Pfizer Inc (Employee, Shareholder)
18. An Easy-to-Implement Clinical-Trial Frailty Index Based on Accumulation of Deficits: Validation in Zoster Clinical Trials
Authors: Andrew Melissa K , Matthews Sean , Kim Joon Hyung , Riley Megan , Curran Desmond
Published: December 2021

Background

The impact of frailty on the efficacy and safety of vaccines and therapeutic interventions is increasingly recognized, yet assessment of frailty in clinical trials is often considered logistically challenging. We developed the retrospective Clinical Trial Frailty Index (CT-FI), using baseline medical history and patient reported outcomes collected via standard instruments (Short Form Survey-36 and Euro Quality of Life-5 Dimension) in two clinical trials of the adjuvanted recombinant zoster vaccine (RZV, ZOE-50 [NCT01165177] and ZOE-70 [NCT01165229]). This post-hoc analysis aimed to show that CT-FI is a robust measure that may be used in any analysis where sufficient patient data has been collected in a clinical trial.

Methods

Items included in the CT-FI were scored from 0 to 1, summed for each participant and divided by the total number of potential deficits. CT-FI was validated using descriptive methods verifying distribution and age- and sex-associations in relation to established FI characteristics, Cox regressions in relation to fatal outcomes hypothetically related to frailty, and re-sampling methods (Jackknife and Bootstrap procedures) within the FI to demonstrate robustness to inclusion/exclusion of specific individual variables.

Results

The CT-FI distribution followed a gamma distribution with a range of 0 to 0.695; the distribution shifted to the right with age. The age-related slope of mean deficit accumulation per year increased with chronological age and was higher for women than men. The rate of mean deficit accumulation was 0.0025 for women vs 0.0016 for men < 70 years of age, and this increased to 0.0058 for women vs 0.0047 for men ≥70 years of age. In univariate and multivariate Cox regression survival analyses, FI, chronological age and sex were significant predictor factors for mortality. The Jackknife and Bootstrap re-sampling methods showed that the performance of CT-FI was not sensitive to inclusion/exclusion of specific individual or groups of variables, demonstrating the robustness of this methodology.

Conclusion

The current analysis validates that CT-FI, an easy-to-implement FI, is a robust method which allows retrospective/prospective evaluation of clinical outcomes by frailty status in clinical trials.

Disclosures

Melissa K. Andrew, MD, PhD, GSK (Grant/Research Support)Pfizer (Grant/Research Support, Advisor or Review Panel member)Sanofi (Consultant, Grant/Research Support, Advisor or Review Panel member)Seqirus (Advisor or Review Panel member) Sean Matthews, MSc, GSK (Independent Contractor) Joon Hyung Kim, MD, GSK group of companies (Employee, Shareholder) Megan Riley, PhD, GSK group of companies (Employee, Shareholder) Desmond Curran, PhD, The GSK group of companies (Employee, Shareholder)
29. Impact of Antimicrobial Stewardship Intervention on Unrestricted Meropenem Use Upon Transitions of Care
Authors: Zaidan Noor , Britt Rachel S , Reynoso David , Enwere Emmanuel , Rucker Kathryn , Scott Ferren R
Published: December 2021

Background

Broad-spectrum antimicrobials, like carbapenems, are often initiated empirically and can be continued for long periods of time, which may increase rates of multi-drug resistant organisms. Antimicrobial stewardship programs (ASP) have been shown to decrease the duration of antimicrobial therapy. Since July 2017 at UTMB Health, meropenem use has been restricted to infectious diseases and intensive care unit (ICU) providers. This study evaluated the impact of an electronic medical record (EMR)-based ASP intervention on meropenem days of therapy (DOT) in patients transitioning from the ICU to the general floors.

Methods

Patients aged at least 18 years with an active medication order for meropenem upon transition from an ICU to a medical/surgical unit were included. Once transitioned, the active meropenem order appeared in the “review” column of the pharmacists’ queue. Pharmacists contacted the primary team, requested infectious diseases or ASP approval to continue therapy, and documented communication in the chart. Data for the pre- and post-intervention groups was collected retrospectively for the months of November 2017 to April 2018 and March 2020 to August 2020. The primary outcome of the study was meropenem DOT after transition from the ICU to the medical/surgical unit. Secondary outcomes of the study included meropenem total DOT, total number of meropenem doses after transfer to the medical unit, 30-day all-cause mortality, and 30-day readmission.

Results

A total of 163 patients were evaluated in both the pre-intervention (n = 87) and post-intervention groups (n = 76). Median meropenem DOT after transition of care (3 days vs. 2 days, P = 0.0004) and number of meropenem doses after transition (6 doses vs. 4 doses, P = 0.014) were significantly lower after TOC intervention implementation. However, total meropenem DOTs were not different at 5 days in both groups. Recommendations for de-escalation or discontinuation were accepted 60% of the time among providers.

Conclusion

An EMR-based ASP intervention did decrease meropenem DOT after patients were transitioned from the ICU to the medical/surgical floors. Results of the meropenem EMR-based ASP intervention may be used to expand to other broad-spectrum antimicrobials/antifungals in patients transitioning levels of care.

Disclosures

All Authors: No reported disclosures
32. Impact of a Four-Year Antimicrobial Stewardship Program on Antimicrobial Resistance
Authors: Chrysou Konstantina , Zarkotou Olympia , Mamali Vasiliki , Rekleiti Nektaria , Themeli-Digalaki Katina , Chrysos Georgios , Tsakris Athanasios , Pournaras Spyridon
Published: December 2021

Background

Antimicrobial resistance (AMR) is an increasing threat to public health and antimicrobial consumption is a primary driver of resistance. Many studies have shown that the implementation of an antibiotic stewardship program (ASP) improves prescribing of antibiotics and can reduce AMR. Purpose of the study was to assess the impact of a successful ASP, implemented for four years, on AMR in our 427-bed tertiary general hospital.

Methods

We monitored pharmacy data for the years 2015 (pre-intervention) and 2016-2019 (post-intervention) for antibiotic consumption (DDD/100 bed-days) and resistance rates. AMR data were obtained from the clinical microbiology laboratory’s electronic database. To achieve the goals of ASP we used a range of interventions as pre-authorization strategy for the protected antibiotics (tigecycline, carbapenems, quinolones, glycopeptides, daptomycin, colistin, linezolid), prospective audit and feedback with direct intervention, de-escalation or switch from iv to oral administration and appropriate selection and duration of chemoprophylaxis in surgery.

Results

Significant reductions were observed for: total antibiotics, colistin, carbapenems, quinolones and tigecycline consumption during study period. Significantly lower resistance rates were documented in 2019 compared to 2015 for Pseudomonas aeruginosa and for Klebsiella pneumoniae. As for Acinetobacter baumannii isolates, which in our hospital are highly-resistant exhibiting >90% resistance to carbapenems, no significant changes were noted during the study period. Infections caused by Gram-positive pathogens are less prevalent in our hospital. Lower rates of vancomycin-resistant enterococci were noted after the implementation of our ASP (30.4% in 2019 vs. 50.0% in 2015 for E. faecium and 0.6% vs. 6% for E. faecalis, respectively), whereas methicillin-resistant S. aureus isolates increased (40% in 2019 vs. 31.1% in 2015), possibly because most of these infections were not hospital-acquired.

Resistance rates of Pseudomonas and Klebsiella

Conclusion

Our ASP was successful in reducing antibiotic consumption and AMR for important pathogens.

Disclosures

All Authors: No reported disclosures
48. Local Implementation of an Antibiotic Stewardship Intervention for Asymptomatic Bacteriuria Through Centralized Facilitation Required Minimal Costs and Effort
Authors: Rajan Suja S , Grigoryan Larissa , Van John , Lichtenberger Paola , Patel Payal K , Shukla Bhavarth , Calub Feliza , Brown Nui G , Nguyen Phuong Khanh , Hershey Cheryl , Drekonja Dimitri M , Graber Christopher J , Trautner Barbara
Published: December 2021

Background

The cost of an antibiotic stewardship intervention is an important yet often neglected factor in antibiotic stewardship research. We studied the costs associated with successful implementation of the “Kicking CAUTI” intervention to decrease treatment of asymptomatic bacteriuria (ASB).

Methods

A central coordinating site facilitated roll-out of an audit and feedback intervention to decrease unnecessary urine cultures and antibiotic treatment in patients with ASB in four Veterans Affairs medical centers. Each site had a physician site champion, a part-time research coordinator, and 1-2 additional participants (often pharmacists). Participants kept weekly time-logs to collect the minutes associated with intervention tasks, and percent full-time effort (FTE) and costs were computed. For weeks with missing logs the average minutes for each activity associated with each type of professional was imputed. Salary information was obtained from the Bureau of Labor Statistics and Association of American Medical Colleges.

Results

Research coordinator time comprised of majority of the personnel time, followed by the physician site champions (Figure 1). Each intervention site required about 10% FTE/year of a research coordinator, and 3.5% FTE/year and 3.8% FTE/year of a physician and pharmacist respectively. The coordinating site required 37% FTE/year of a research coordinator, and 9% FTE of a physician to spearhead the intervention. Research coordinators predominantly spent their time on chart-reviews and project coordination. Physician champions predominantly spent their time on delivering audit and feedback and project coordination. The intervention cost USD 22,299/year per site on average, and USD 45,359/year for the coordinating site.

Conclusion

The Kicking CAUTI intervention was successful at reducing urine cultures and associated antibiotic use, with minimal time from the local team members. The research coordinators’ time was primarily spent on collection of research data, which will not be necessary outside of a research project. Our model of centralized facilitation makes economic sense for widespread scale-up and dissemination of antibiotic stewardship interventions in integrated healthcare systems.

Disclosures

Barbara Trautner, MD, PhD, Genentech (Consultant, Scientific Research Study Investigator)
56. High Frequencies of Adverse Drug Events with Intravenous vs Oral High-Dose Trimethoprim-Sulfamethoxazole: An Opportunity for Antibiotic Stewardship
Authors: Vuong Lisa , Davis Susan L , Davis Susan L , Jedinak Tyler , Medler Corey , Zofchak Kristen , Veve Michael P , Kenney Rachel
Published: December 2021

Background

Trimethoprim-sulfamethoxazole (TMP-SMX) is a high-bioavailability antibiotic associated with potentially serious adverse drug events (ADE). The objective of this study was to evaluate the safety of intravenous (IV) and oral (PO) high-dose TMP-SMX.

Methods

IRB-approved retrospective cohort of hospitalized patients from January 2016 to November 2020. Inclusion: ≥ 18 years old and > 72 hours of renally adjusted high-dose TMP-SMX defined as ≥ 5 mg/kg/day of TMP. Exclusion: prophylaxis. Endpoints during treatment: hyponatremia with sodium < 135 mmol/L, hyperkalemia with potassium > 5 mmol/L, serum creatinine increase of ≥ 0.3 mg/dL or 1.5-1.9 times from baseline, and fluid overload on physical exam. Descriptive and bivariate statistics were performed.

Results

Each group included 50 patients (Table 1). Intensive care unit patients comprised 82% IV TMP-SMX compared to 32% PO. Most common infection: respiratory tract 86% IV and 68.1% PO. Most common organisms were Stenotrophomonas maltophilia (52% IV and 18% PO) and Pneumocystis jiroveci (16.3% IV and 62% PO). Median (IQR) days of inpatient therapy: 6 (5-7.5) PO vs. 7.5 (6-11.3) IV. Median (IQR) days of total duration: 9 (6-21.5) PO vs. 12 (7.8-14) IV (p=0.93). IV group: 88% of patients received >1 liter of D5W daily. Median (IQR) liters of D5W daily was 1 (1-1.5). 56% had a diuretic added, and 38% had a diuretic dose increase. Majority of patients (78%) on IV were taking other oral medications. 100% patients experienced any adverse event with IV vs. 70% with PO (unAdjOR 2.43; 95% CI 1.89-3.13). Most common ADE in both groups: hyponatremia, hyperkalemia, and elevated creatinine. Hyponatremia: 92% with IV and 32% with PO (unAdjOR 24.44; 95% CI 7.50-79.68). Edema on physical exam, an ADE specific to IV TMP-SMX, was the third most common side effect in the IV group. Relative changes from baseline in sodium, potassium, and creatinine from those who experienced hyponatremia, hyperkalemia and elevated creatinine were listed in Table 2.

Table 1. Baseline and Clinical Characteristics

Table 2. Adverse Effects

Conclusion

Patients on IV TMP-SMX therapy were more likely to experience an ADE compared to PO, likely driven by the high volume of free water. Most patients on IV TMP-SMX were on other PO medications, suggesting a missed stewardship opportunity for IV to PO conversion to reduce patient harm.

Disclosures

Susan L. Davis, PharmD, Nothing to disclose Michael P. Veve, Pharm.D., Cumberland (Grant/Research Support)Paratek Pharmaceuticals (Research Grant or Support) Rachel Kenney, PharmD, Medtronic, Inc. (Other Financial or Material Support, spouse is an employee and shareholder)
59. Impact of Pharmacist-Led De-Escalation of MRSA Therapy Using MRSA Nasal PCR
Authors: Salvatus Marc , Jung Hemi , Eskandarian Romic , Lee Su
Published: December 2021

Background

Experts suggest that a highly sensitive MRSA nasal PCR can be used to rule out MRSA pneumonia with a negative predictive value greater than 95%. At Adventist Health Glendale (AHGL), the MRSA nasal PCR had a 97% negative predictive value. Pharmacist-led de-escalation of MRSA therapy using MRSA nasal PCR may reduce unnecessary MRSA coverage, patient adverse events, and medication costs. The purpose of this study was to assess the impact on duration of antimicrobial therapy of pharmacist-driven de-escalation of MRSA-targeted antibiotics in pneumonia using MRSA nasal PCR.

Methods

This was a prospective quasi-experimental study (Oct 2018 – Mar 2019 vs. Oct 2019 – Mar 2020) at AHGL, a 515-bed acute care community hospital in Los Angeles, CA, which included adults on MRSA pneumonia agents (either IV vancomycin or IV/PO linezolid). Upon receiving CPOE orders of these MRSA-targeted therapies for pneumonia, the pharmacist ordered a MRSA nasal PCR per protocol for eligible patients, followed up with the results of the MRSA nasal PCR, and recommended to discontinue MRSA therapy if the MRSA nasal PCR was negative. This study received an exemption determination from AHGL IRB.

Results

The total number of patients in the pre-protocol group was 97, and 155 in the post-protocol group. There was a statistically significant decrease in the median duration of MRSA pneumonia agents from the pre-protocol group compared to the post-protocol group (3 days vs. 2 days, P-value = 0.0004). Additionally, there was a statistically significant decrease in the median hospital length of stay from the pre-protocol group compared to the post-protocol group (9 days vs. 7 days, P-value = 0.02).

Conclusion

Implementation of a protocol involving pharmacist-led de-escalation of MRSA-targeted antibiotics for pneumonia utilizing MRSA nasal PCR led to significant decreases in both duration of therapy of MRSA-targeted antibiotics and length of hospital stay.

Disclosures

All Authors: No reported disclosures
70. Impact of the Accelerate Pheno™ System on Clinical and Antimicrobial Outcomes among Inpatients with Gram-Negative Bacteremia at a 528-bed Community Teaching Hospital
Authors: DePasquale William P , Staicu Mary L , Stainton Sean , Laguio-Vila Maryrose R , Hite Mindee , Berg Deanna
Published: December 2021

Background

Traditional methods in blood culture analysis require 24-72 hours to yield identification (ID) and antimicrobial susceptibility testing (AST) results, which may contribute to the use of empiric broad-spectrum antibiotic therapy. Hence, the primary objective of this study was to determine the impact of rapid blood culture analysis with the Accelerate Pheno™ system (AXDX) on time to antibiotic de-escalation.

Methods

This was a single center, case-control analysis of adult inpatients with E. coli or Klebsiella spp. bacteremia. Cases were prospectively identified by the antimicrobial stewardship team between August and October 2020 after the implementation of AXDX in July 2020. Subjects were matched to historical controls (July 2018-July 2020) based on age (± 3 years), gender, source of infection, and identified organism. The primary outcome was time to antibiotic de-escalation and time to oral antibiotic therapy from the time of positive blood cultures. Secondary outcomes included hospital length of stay, 30-day mortality, 30-day readmission, and 60-day C. difficile infection. Outcomes were compared using descriptive and inferential statistics.

Results

Of 33 cases identified, 30 (91%) were matched with historical controls. E. coli bloodstream infection was identified in 24 (80%) subjects while Klebsiella spp. was identified in 6 (20%) subjects. The average age was 66 years (SD ± 19) and there was an even distribution of males and females in both groups. Other demographics were similar between groups. The median time to species identification [14 hours (IQR 13 – 18) vs 34 hours (29 – 39), p< 0.001) and AST [20 hours (19 – 37) vs 45 hours (38 – 51), p< 0.001] from laboratory registration was significantly shorter in cases. The average time to antibiotic de-escalation was 1.7 (±1.2) days for cases compared to 2 (±1.3) days for controls (p=0.460). Median time to oral antibiotic therapy from positive blood cultures was 2.9 (1.8 – 4.7) days for cases and 3.4 (2.5 – 5.1) days for controls (p=0.166). There were no significant differences in the secondary outcomes.

Conclusion

AXDX did not appear to have a significant impact on time to antibiotic de-escalation and time to oral antibiotic therapy. However, time to organism ID and AST results were significantly shorter in the AXDX cohort.

Disclosures

All Authors: No reported disclosures
86. Access to Antimicrobial Susceptibility Testing for Novel Gram-Negative Antibiotics
Authors: Lee Yuman , Kim Juliette , Bradley Nicole
Published: December 2021

Background

Antimicrobial susceptibility testing (AST) is critical in identifying the optimal antimicrobial regimen for individual patients with serious gram-negative infections. Limitations to AST for newly developed antibiotics include the lack of commercially available AST methods, challenges of implementation due to regulations, and delays in obtaining results. The purpose of this study was to evaluate the access to AST for cefiderocol (FDC), imipenem-relebactam (IPR), meropenem-vaborbactam (MEV), and eravacycline (ERV) in hospitals across the U.S.

Methods

An electronic survey was distributed to the American College of Clinical Pharmacist Infectious Diseases Practice and Research Network in May 2021. Hospital baseline demographics and current practices were collected.

Results

Based on 50 responses, specimens were sent to in-house microbiology labs (37, 74%), core microbiology labs (8, 16%), and 3rd party reference microbiology labs (5, 10%). AST for FDC was performed by 13 (35%) in-house labs, 4 (50%) core labs, and 1 (20%) reference lab. AST for IPR was performed by 11 (30%) in-house labs, 2 (25%) core labs, and 1 (20%) reference lab. AST for MEV was performed by 25 (68%) in-house labs, 3 (37.5%) core labs, and 1 (20%) reference lab. AST for ERV was performed by 1 (20%) in-house lab, 1 (20%) core lab, and 0 reference labs. 15 (30%) respondents were not able to get AST for any of the novel agents at their respective microbiology labs. Turn-around-times (TATs) for FDC, IPR, MEV, and ERV were ≥72 hours for 33 (66%), 35 (70%), 21 (42%), and 35 (70%) hospitals, respectively. When compared with 3rd party reference labs, in-house labs with the ability to perform AST for these novel agents had significantly shorter TATs (p< 0.05). The average number of requests for AST for these novel agents was 20 times a year with an average of 113 minutes spent per patient on the coordination of AST.

Conclusion

Access to AST for these novel agents varied across hospitals in the U.S. Nearly 1/3 of the respondents were not able to obtain AST for these agents at all. Long TATs exist and a great deal of time is spent per patient for coordinating AST for these novel agents. There is a crucial need for a multidisciplinary, collaborative approach to resolve the challenges in obtaining AST for newly developed antibiotics to provide patient care.

Disclosures

All Authors: No reported disclosures
87. Effectiveness of a Best Practice Advisory in Reducing Inappropriate Urine Cultures
Authors: Cooper Margaret , Shihadeh Katherine C , Hussain Cory , Jenkins Timothy C
Published: December 2021

Background

Inappropriate urine cultures can contribute to overutilization of antibiotic treatment for asymptomatic bacteriuria. The objective of this study was to evaluate the appropriateness of urine cultures and the impact of a clinical decision support (CDS) intervention.

Methods

The CDS intervention involved embedding three questions in the urine culture order: whether the patient has fever, leukocytosis or urinary symptoms. When the answer to all three questions is no, a best practice advisory (BPA) alerts the provider that the patient may not meet criteria for a urine culture and suggests cancellation of the order. Cultures obtained in patients experiencing fever, leukocytosis, or urinary symptoms, and those who were pregnant, undergoing invasive urologic procedure, or < 3 years old were classified as appropriate. We performed a quasi-experimental study assessing appropriateness of urine cultures before and after implementation of the BPA. The pre-intervention period was 5/9/19 to 7/31/20 and the intervention period was 2/3/21 to 4/27/21. Random samples of 100 cases from pre- and post-intervention were reviewed to assess appropriateness.

Results

There were 12,679 and 8,270 urine cultures performed pre-intervention and post-intervention, respectively. In 100 cases reviewed pre-intervention, 74% of the cultures were appropriate. Of these, 54% were ordered due to fever or leukocytosis, 50% due to urinary symptoms, and 12% in pregnant women.

Post-intervention, the BPA fired on 458 orders and 106 (23%) were subsequently discontinued. Of the 100 cases reviewed post-intervention, 5 orders were discontinued after the BPA fired. Of the remaining 95 cultures, 78% were appropriate. Of these, 41% were ordered for fever or leukocytosis, 69% for urinary symptoms, and 11% in pregnant women. The change in the proportion of appropriate cultures pre- and post-intervention was not statistically significant (74% vs 78%, respectively, p=0.906).

Conclusion

In nearly one quarter of urine cultures performed, there was not an appropriate indication. Our intervention led to cancellation of 23% urine culture orders and resulted in an absolute increase in 4% of the cultures being ordered appropriately. However, the change in appropriateness was not statistically significant.

Disclosures

All Authors: No reported disclosures
89. Follow-Up Blood Cultures (FUBC) in the Management of Gram-Negative Bacilli (GNB) Bloodstream Infections (BSIs): Frequently Obtained and Rarely Helpful
Authors: Robinson Evan D , Cox Heather , Mathers Amy J
Published: December 2021

Background

While GNB BSIs remain a major cause of morbidity and mortality, no clear guidelines exist on the utilization of FUBCs to guide management. Despite the recognition of persistent bacteremia as a risk factor for increased mortality, early studies suggested FUBCs were low yield in this setting, and thus had low utility. More recently, some controversy has arisen with multivariate analyses suggesting FUBC acquisition may be associated with lower mortality. We sought to characterize the utilization and yield of FUBCs for GNB BSIs at our institution.

Methods

We performed a retrospective review of 514 episodes of consecutive blood cultures from unique adult inpatients with GNB BSI between July 2017-July 2019. Exclusion criteria included prior positive culture, polymicrobial Gram stain, or discharge, death, or comfort measures only within 24 hours of Gram stain. FUBCs were defined as blood cultures collected between 24 hours to 7 days after the index blood culture. Baseline clinical and microbiologic characteristics were compared between groups, as well as clinical outcomes.

Results

Of 514 episodes, 338 (66%) had FUBCs performed, with a median of 2 FUBCs/episode. The majority of FUBCs (322/338; 95%) were negative, with 9 (3%) yielding the same organism and 9 (3%) yielding a different organism. Most initial FUBCs were obtained prior to index antimicrobial susceptibility results (227/338; 67%). Patients with FUBCs performed had a higher median Pitt bacteremia score (2 vs 1; p = 0.015) and were more likely to have hospital onset (36% vs 22%; p = 0.002), severe neutropenia (16% vs 4%; p < 0.001) and a catheter-associated source (13% vs 4%; p = 0.001). 30-day mortality did not differ between patients with or without FUBCs (10% vs 11%; p = 0.84).

Conclusion

FUBCs were frequently obtained, but were of low yield even in comparison to recent similar studies. Though FUBCs were performed in more severe cases, a difference in mortality was not observed. Delaying the decision of whether to obtain FUBCs until after index antimicrobial susceptibility results are available would reduce unnecessary testing in most cases. Further study could better define where FUBCs after antimicrobial susceptibility testing would be most helpful.

Disclosures

All Authors: No reported disclosures
90. Deimplementation: Use of Electronic Clinical Decision Support to Reduce Unnecessary Erythrocyte Sedimentation Rate (ESR) Ordering
Authors: Fatemi Yasaman , Burns Julianne , Polsky Tracey , Nord Ellen , Coffin Susan
Published: December 2021

Background

In recent years, several de-implementation initiatives have focused on diagnostic testing. One such initiative, the Choosing Wisely campaign, recommends against routine use of erythrocyte sedimentation rate (ESR) for assessment of acute undiagnosed inflammation or infection. With the development of newer biomarkers of inflammation, particularly C-reactive protein (CRP), there is a decreasing role for ESR in screening for acute-onset conditions; however, ESR continues to be commonly ordered.

Methods

We examined ESR and CRP ordering practices at the Children’s Hospital of Philadelphia (CHOP) from July 2019 to July 2020 and found that 80% of ESR orders were placed concurrently with an order for CRP. We aimed to reduce ESR ordering by 20% at CHOP by using electronic clinical decision support in the form of embedded order guidance for ESR orders placed in the Emergency Department (ED) and inpatient setting. We examined the effect of the clinical decision support by assessing ESR ordering rate, defined by ESR orders per monthly patient days for the inpatient setting and ESR orders per monthly ED visits for the ED setting. We then examined differences in ordering rates using a quasi-experimental model with a concurrent control (basic metabolic panel).

ESR Electronic Clinical Decision Support Intervention

Inpatient and ED versions of the embedded electronic clinical decision support for ESR orders.

Results

Prior to implementation of the electronic decision support intervention, the median monthly rate of ESR orders was 13.6 per 1000 patient days and 70.3 per 1000 ED visits. During the initial month after implementation, we found that ESR ordering was 12.5 in inpatient and 46.4 in ED, reflecting decreased rates of ordering. The median monthly rate of basic metabolic panel orders (concurrent control) was 194.5 per 1000 patient days and 110.0 per 1000 ED visits. This was unchanged after intervention.

Conclusion

We conclude that electronic clinical decision support is a potentially effective deimplementation method for improving diagnostic test utilization, even with non-disease specific testing such as inflammatory markers. However, continued post-implementation data monitoring and analysis is needed to determine if this is a true difference and sustainable trend.

Disclosures

All Authors: No reported disclosures
95. Reduced Antibiotic Duration Defaults in Outpatient Automated Dispensing Cabinets Change Antibiotic Prescribing Habits in a Tertiary VA Healthcare System
Authors: Newman Nicholas J , Stiefel Usha , Wenzell Robert C , Papell Daniel , Cooney Jeffrey , Sims Sharanie , Shumaker Amy H , Akpoji Ukwen
Published: December 2021

Background

Ten percent of adult, outpatient visits result in an antibiotic prescription (Rx). At the start of our intervention, our VA healthcare system consisted of 13 community-based outpatient clinics (CBOCs), 9 of which did not have an onsite pharmacy but utilized automated dispensing cabinets (ADCs) for prepackaged outpatient Rxs. ADC antibiotic orders are generated from electronic medical record (EMR) order sets. The stewardship team shortened the durations of 5 antibiotics in the ADC order sets to make them consistent with current literature and guidelines. We assessed the impact of these changes on antibiotic prescribing habits.

Methods

We compared outpatient antibiotic Rx data between 10/1/2018-9/30/2019 (pre-intervention) and 10/1/19-9/30/20 (post-intervention) from 8 CBOCs with ADCs (1 closed during the pandemic). Amoxicillin-clavulanate 875/125mg (AMC), cephalexin 500mg (CPH), levofloxacin 500mg and 750mg (LEV 500 and LEV 750), and sulfamethoxazole-trimethoprim 800/160mg (SXT) prescription durations were all reduced by 3 days. Process metrics included days supplied/1000 prescriptions (DS/1000 Rx), median DS, and ADC utilization rates. We used Mann-Whitney U and correlation statistical analyses to assess differences and associations.

Results

The DS/1000 Rx of antibiotics with a default duration change decreased in the post-intervention phase for CBOCs with ADCs (AMC, -25.4%; CPH, -21.1%; LEV 500, -18.9%; LEV 750, -28.0%; SXT, -27.4%). The median DS for these antibiotics all reduced by 3 days in concordance with new ADC prescriptions defaults (AMC, 10 vs 7 days, P< 0.001; CPH, 10 vs 7 days, P< 0.001; LEV 500, 8 vs 5 days, P< 0.001; LEV 750, 8 vs 5 days, P< 0.001; SXT 10 vs 7 days, P< 0.001). Due to COVID-19, 7/8 ADC CBOCs closed for in-person visits from 3/20/20-5/4/20. ADC utilization was inversely proportional to DS/1000 Rx for most antibiotics (R: -0.51 to -0.77) except SXT.

Conclusion

EMR-driven reductions in ADC default Rx durations led to a corresponding decrease in overall outpatient antibiotic prescribing. Higher DS/1000 Rx were often associated with lower ADC utilization. Informatics-driven antibiotic interventions may be potential outpatient stewardship tools to increase guideline-concordant prescribing across multisite healthcare systems.

Disclosures

Sharanie Sims, PharmD, AbbVie (formerly Allergan) (Speaker’s Bureau)