bluuebunny/crossref_metadata_2025 huggingface dataset:
1720. In Vitro Activity of Aztreonam-Avibactam and Comparator Agents Against Enterobacterales from Patients with Urinary Tract Infections Collected During the ATLAS Global Surveillance Program, 2017-2020
Authors: Estabrook Mark , Arhin Francis , Sahm Daniel F
Published: December 2022

Background

β-lactamase-producing Enterobacterales (Eba) frequently carry resistance mechanisms for multiple drug classes, limiting treatment options. Avibactam (AVI) inhibits class A, class C, and some class D serine β-lactamases, while aztreonam (ATM) is refractory to hydrolysis by class B metallo-β-lactamases (MBLs). ATM-AVI is being developed for use against drug-resistant isolates of Eba, especially those co-producing MBLs and serine β-lactamases. This study evaluated the in vitro activity of ATM-AVI and comparators against Eba collected in 2017-2020 from patients with urinary tract infections (UTI) as part of the ATLAS global surveillance program.

Methods

Non-duplicate clinical isolates were collected from 239 sites in 55 countries in Europe, Latin America, Asia/Pacific (excluding mainland China and India), and Middle East/Africa. Susceptibility testing was performed by CLSI broth microdilution and interpreted using CLSI 2022 and FDA (tigecycline) breakpoints. PCR and sequencing were used to determine the β-lactamase genes present in all isolates with meropenem MIC >1 µg/mL, and Escherichia coli, Klebsiella spp. and Proteus mirabilis with ATM or ceftazidime MIC >1 µg/mL.

Results

Based on MIC90 values, ATM-AVI was at least as active as every comparator agent tested against all 15085 Eba isolates collected from UTI (0.12 µg/ml; table), with only five isolates testing with MIC values >8 µg/ml (not shown). Against resistant subsets of isolates, MIC90 values for ATM-AVI were 0.25-0.5 µg/ml, 4- to 8-fold lower than any comparator tested. Against MBL-positive isolates, ATM-AVI MIC values ranged from ≤0.015-2 µg/ml with the exception of one Escherichia coli isolate testing with an MIC value of 16 µg/ml that carried NDM-5, CMY-145, CTX-M-55 and TEM (not shown).

Conclusion

Based on MIC90 values, ATM-AVI was the most potent agent tested against drug-resistant and MBL-positive subsets of Eba collected from UTI. Based on the potent in vitro activity of ATM-AVI, continued development of this combination for treatment of UTI caused by drug-resistant Eba is warranted.

Disclosures

All Authors: No reported disclosures.
1733. Stability of Imipenem/Cilastatin/Relebactam under Different Temperature and Administration Conditions
Authors: Ghazi Islam , Alramany Diaa , Harb Gehan , Nicolau David
Published: December 2022

Background

Imipenem/Cilastatin/Relebactam is an FDA-approved combination antibiotic indicated for resistant infections. There is a practical need to extend the shelf life of parenterals given to patients with such life-threatening infections in the hospital setting. The reconstituted drug's shelf life can be extended by storing at subzero temperatures to slow the degradation kinetics. Package insert indicate stability is 2 hrs at room temperature and refrigeration up to 24 hr. The study aims to determine the stability of the combination in polyvinyl chloride (PVC) infusion (IV) bags when stored at room temperature, refrigerated in addition to continuous infusion CADD pumps.

Methods

Drug vials (Merck & Co) were reconstituted to 5mg/mL (imipenem) in a 100mL normal saline. To avoid further degradation, samples were collected and mixed 1:1 with stabilizing buffer, then frozen at -80 °C within 5 minutes. For room temperature stability, 6 bags were prepared and stored at (24°C). 0.5ml samples were collected at 0, 2, 4, 6, 8, 12, 24 h from each bag at each time point. For refrigeration stability, 6 bags were prepared and refrigerated at 4 °C. At each time point (24, 36, 48, 60, 72, 84, 96,108, 120h), a sample of 0.5-mL is taken from each bag and frozen at −80 °C. For continuous ambulatory drug delivery (CADD) infusion devices stability, the reconstituted drug is loaded to 2g/200 mL cassettes (for 24-hr infusion) continuous infusion and 1g/100mL (for 12-hr infusion). The cassettes are immediately attached to the infusion pump and placed in a cold pouch with gel packs. After the initial 0.5 mL, 0-h samples from each pump, the pumps are sampled at 4, 8,12, 16, 20, and 24 hours for 2g/ 200mL cassettes and 2, 4, 8, 12 h for 1g/100 mL. Cut off for stability was set at 90% of the original concentration. Chemical assay was performed by a validated HPLC method.

Results

See tables Table 1:CADD pumps, concentrations are in mg/mL. Imi; imipenem, Rel; relebactam, Cil; Cilastatin, CADD; continuous ambulatory delivery device, SD; standard deviationTable 2:PCV bags, concentrations are in mg/mL. Imi; imipenem, Rel; relebactam, Cil; Cilastatin, PVC; polyvinyl chloride, SD; standard deviation

Conclusion

Imipenem/relebactam/cilastatin drug product was stable for 12 hrs in CADD pumps 100mL, 16 hrs in 200 mL, 108 hours in refrigerated PVC bags and 12 hrs at room temperature. The extended stability data will assistant pharmacy departments in optimizing drug preparation and storage, nursing time and minimize drug waste improving overall cost and efficiency of drug administration.

Disclosures

Islam Ghazi, PharmD, Merck And Co Inc: Grant/Research Support David Nicolau, PharmD, Marck and Co Inc: Advisor/Consultant|Marck and Co Inc: Grant/Research Support.
1756. Prescriber Adherence to System-Wide Urinary Tract Infection Guidelines in Ambulatory Care Clinics
Authors: Revolinski Sara , Michels Samuel , Olexia Deanna , Fermanich Katherine , Fermanich Katherine
Published: December 2022

Background

Antimicrobial stewardship (AMS) practices are well established in acute care, only recently expanding into ambulatory care settings. It has been estimated that 80-90% of antibiotic use occurs in the ambulatory setting with up to 52% of that use being unnecessary. Urinary tract infections (UTIs) are commonly treated in ambulatory settings, and drug selection and duration of therapy vary among different practices. Our study evaluated the impact of a system-wide guideline and prescriber education, two recommended AMS strategies, on antibiotic utilization for UTIs in the ambulatory setting.

Methods

This retrospective study evaluated female adult patients prescribed an antibiotic for acute uncomplicated cystitis by a primary care provider at a clinic within our organization between January and March 2021. System-wide UTI treatment guidelines were implemented in November 2020, with live education delivered to primary care prescribers in December 2020. The primary objective of this study was to assess prescriber adherence to system-wide guidelines. The secondary objective was to evaluate utilization of antibiotic regimens for treatment of acute uncomplicated cystitis.

Results

A total of 100 patients were evaluated. Guideline adherence was met in 49% of patients. The primary reason for guideline non-adherence was duration of therapy, which was inappropriate (too long) in 42% of patients. Nitrofurantoin, the first-line antibiotic recommendation on the system-wide guideline, was the antibiotic prescribed most frequently (48%), but was the antibiotic of choice in 90% of patients. Sulfamethoxazole/trimethoprim was prescribed in 35% of patients and was most often prescribed correctly with respect to appropriate dose and duration of therapy (60%), followed by nitrofurantoin (54%). Recurrent cystitis within 30 days occurred in 11% of patients.

Conclusion

Implementation of a system-wide guideline and prescriber education for treatment of UTIs in the ambulatory setting identified areas for future optimization of antibiotic use, namely first line antibiotic selection and duration of therapy. This data will be shared with our prescribers to continue to encourage guideline-adherent antibiotic use.

Disclosures

All Authors: No reported disclosures.
1770. Effects of Acculturation and Social Norms on Intention to use Antibiotics without a Prescription among Hispanic or Latino individuals
Authors: Alquicira Osvaldo , Trautner Barbara , Raphael Jean , Salinas Juanita , Barning Kenneth , Mahmood Hammad , Porter Thomas , Street Richard , Lopez-Alonso Moramay , Paasche-Orlow Michael K , Grigoryan Larissa
Published: December 2022

Background

The use of antibiotics obtained without a prescription (non-prescription use) in the United States (U.S.) may contribute to antimicrobial resistance. We hypothesized that among Hispanic/Latino patients, the intention to use non-prescription antibiotics would be associated with: [1] lower acculturation (preference to socialize with Hispanic/Latinos) and [2] having friends or relatives who use antibiotics without contacting a doctor (social norms).

Methods

We conducted a survey on the factors that impact Hispanic/Latino patients’ decisions to use non-prescription antibiotics in safety-net primary care clinics and private emergency departments in the greater Houston, Texas area between January 2020 and June 2021. Surveys were read to patients in English or Spanish and queried patient, health system, and clinical encounter factors.

Results

Of 263 Hispanic/Latino patients, 59% completed the survey in Spanish and 41% in English (Table 1). Overall, 47% reported previous non-prescription antibiotic use, and 36% professed intention to hypothetically obtain and use non-prescription antibiotics, if feeling sick, from one or more of three sources (bought without a prescription in the U. S., from another country, and from friends or relatives).

Lack of health insurance, being surveyed in Spanish, having friends or relatives who use antibiotics without consulting a doctor, and high cost of doctor visits were predictors of intent to use antibiotics bought without a prescription in the U.S. (Table 2). Predictors of intent to use non-prescription antibiotics from other countries included lower acculturation scores (preferring to socialize with Hispanics/Latinos), younger age, having friends or relatives who use antibiotics without consulting a doctor, and reported language barriers to medical appointments. Predictors of intent to use antibiotics from friends and relatives included having friends or relatives who use antibiotics without consulting a doctor, and high cost of doctor visits.

Conclusion

Interventions aimed at reducing non-prescription use in the Hispanic/Latino community should focus on ensuring affordable language concordant healthcare and promoting antibiotic stewardship as a social norm.

Disclosures

Barbara Trautner, MD, PhD, Genetech: Advisor/Consultant Michael K. Paasche-Orlow, MD, MPH, GlaxoSmithKline: Advisor/Consultant Larissa Grigoryan, MD, PhD, Rebiotix Inc: Grant/Research Support.
1777. Shorter Versus Longer Antibiotic Durations for Coagulase-Negative Staphylococcus Catheter-Related Bloodstream Infections and Potential Impact on Antimicrobial Stewardship in a County Hospital
Authors: Arab Niki , Gallardo Huizar Oscar E , Aquije Elizabeth , Cheng Marsha R , Kim Brian , Wong Joseph Isaac S , Jeng Arthur
Published: December 2022

Background

Coagulase negative Staphylococcus (CoNS) is a common cause of catheter-related bloodstream infection (CRBSI). Current guidelines are to provide 10-14 days (d) of antibiotics (abx) plus lock abx in the absence of catheter removal, and if the catheter has been removed, 5-7 d after removal. Olive View UCLA-Medical Center (Sylmar, CA) is an academic county hospital, serving the medical needs of the underserved community. The purpose of this study was to evaluate differences in treatment (tx) durations for CoNS CRBSI on clinical outcomes and evaluate the potential impact on antimicrobial stewardship.

Methods

Single center retrospective chart review from January 2018 to December 2021 on all central line-obtained blood cultures (Bcx) positive for CoNS. Exclusion criteria included suspected contamination or no abx tx, invasive CoNS infection, and concomitant infection treated with abx that have activity against CoNS. Duration of abx tx was divided into two groups: >10 d vs ≤10 d with or without catheter removal and >7 d vs ≤7 d post catheter removal. Primary outcomes assessed were recurrence of CoNS CRBSI within 90 d and 30 d hospital readmission. Secondary outcomes included hospital length of stay (LOS), 30 d all-cause mortality, and days of Bcx positivity. Groups were compared using Wilcoxon rank-sum for continuous variables and Fisher’s exact for categorical variables using Stata (Version 15).

Results

153 positive CoNS central line Bcx were screened, 40 met study inclusion. 37 received vancomycin as initial abx with a median total tx duration of 13.5 d [IQR 8-14] and 9 d [IQR 6-13.5] after line removal. 22 (55%) received total abx duration of >10 d and 18 (45%) received total abx duration of ≤10 d. Baseline characteristics were similar between >10 d and ≤10 d (table 1). There was no significant difference in primary and secondary outcomes, respectively, between >10 d and ≤10 d (table 2). After catheter removal, there were no significant differences in outcomes whether antibiotics were continued for >7 d (n=18) vs ≤7 d (n=15) (table 3). Table 1:Baseline CharacteristicsTable 2:Outcomes according to days of therapyTable 3:Outcomes post catheter removal days of therapy

Conclusion

Abx tx duration of ≤10 d compared with >10 d for CoNS CRBSI did not result in differences in 90 d recurrence and 30 d readmission. Shorter courses of tx for CoNS CRBSI should be considered as a target for antimicrobial stewardship to minimize antibiotic exposure.

Disclosures

All Authors: No reported disclosures.
1779. An Assessment of Antibiotic Treatment Guideline Adherence for Common Infections in a Tertiary Care Hospital with an Established Antimicrobial Stewardship Program in Kathmandu, Nepal
Authors: Adhikari Prabhat , Director Medical , Bhumiratana Adisak , Acharya Subhash , Acharya Upasana , Pant Suman , Silwal Sashi , Dawadi Pratima , Koirala Janak , Gyanwali Pradip , Shrestha Suman
Published: December 2022

Background

Antibiotic treatment guidelines have been increasingly recognized as an effective tool to guide appropriate prescriptions and help curtail antibiotic resistance. We aimed to assess the quality of inpatient antibiotic prescribing practices for common infections in a tertiary centre in Kathmandu.

Methods

We conducted a retrospective monocentric review of medical records of adult inpatients diagnosed with Urinary Tract Infection; Pneumonia; and Skin and soft tissue infection between January 2018 till December 2019. Adherence was defined as the prescription of antibiotics for mentioned infection fulfilling the correct choice, correct dose, and correct duration of therapy.

Flow diagram 1

Medical Records Review to assess adherence to guideline

Results

Clinical records of 354 inpatients were included in the analysis. Overall, 37.9% of antibiotic prescriptions were adherent to guideline recommendations. The non-adherent groups also had a higher proportion of patients in the age group between 45 and 60 years (66%, OR: 1.87, 95% CI: 1.09-3.21, p=0.2) and with the presence of co-morbidities (58%, OR: 0.44, 95% CI: 0.26-0.75, p< 0.1). The department categories, gender, number of comorbidities, infectious disease diagnosis, and history of antibiotic drug allergy had no significant effect reported on adherence. Incorrect selection (20%, or: 0.24, 95% CI: 0.07-0.79, p=0.19) and incorrect antibiotic dosage (21%, OR: 0.26, 95% CI: 0.08-0.82, p=0.02) were prescribed among patients diagnosed with urinary tract infection. Likewise, an incorrect dosage of antibiotics (40%, OR: 0.27, 95% CI: 0.07-0.97, p=0.05) was prescribed for patients with pneumonia. Pneumonia (52%) and urinary tract infection (32%, p< 0.01) had more de-escalations, while the antibiotic spectrum prescribed was significantly broad (81%, p< 0.001).

Study Schema

Conclusion

Our study revealed low adherence despite the availability of the updated guideline for an antibiotic prescription. These data demand an urgent need to confront the antibiotic prescription pattern in the tertiary care centres for tailored interventions to improve adherence to guidelines, particularly focusing on prescriptions of antibiotic types and in the elderly population. It is also an imperative to reduce the broad-spectrum antibiotic exposure to the patients with acute infections guided by the culture reports.

Disclosures

All Authors: No reported disclosures.
1815. Assessment of Therapy Duration for Non-Staphylococcal Gram-Positive Bloodstream Infections
Authors: Gould Alyssa P , Crawford Robert L
Published: December 2022

Background

The optimal duration of antimicrobial therapy for non-staphylococcal Gram-positive (GP) bloodstream infections (BSIs) remains unknown. The purpose of this study was to evaluate clinical outcomes in patients with short (6-10 days) vs. long (11-21 days) duration of therapy (DOT) for non-staphylococcal GP BSIs.

Methods

Adult patients with BSI due to Streptococcus or Enterococcus spp. admitted to a community health system from January 2016 to December 2021 were included in this retrospective chart review. Patients were excluded for polymicrobial BSI, positive culture deemed contamination, infectious source requiring prolonged treatment, DOT < 6 or > 21 days, or transfer, hospice, or death prior to therapy completion. The primary endpoint was 90-day all-cause mortality. Descriptive statistics, chi-square or Fisher’s exact test, and the student t-test were used for data analysis.

Results

Of 3,544 patients identified, 384 were screened and 86 included. There were 71 patients in the long DOT group and 15 patients in the short DOT group. All included patients were on active therapy for the entire DOT. Baseline characteristics were similar except patients in the long DOT group were more likely to have an infectious diseases consultation and a non-pulmonary source of infection (Table 1). All-cause mortality at 90 days was similar between short vs. long DOT groups (0% vs. 3%, p=0.51) (Table 2). The secondary endpoints of 30-day all-cause mortality, 30-day and 90-day BSI recurrence due to the same organism, 30-day readmission, and hospital length of stay were not statistically different between groups (Table 2). The most common pathogen identified in the short DOT group was Streptococcus pneumoniae (n=8), and the most common identified pathogens identified in the long DOT group was Streptococcus agalactiae (n=22), Enterococcus faecalis (n=14), and S. pneumoniae (n=13) (Table 3).

Conclusion

In this retrospective review of non-staphylococcal GP BSIs, there was no statistical difference in clinical outcomes between the short and long DOT arms. Additional research is needed to identify the optimal duration of antimicrobial therapy for non-staphylococcal GP BSIs.

Disclosures

All Authors: No reported disclosures.
1818. Characteristics Associated with Mortality in Patients with Gram-negative Bacteremia in Intensive Care Units
Authors: Shukdinas Alaina , Werzen Alissa , Ali Shereef N , Vyas Nikunj M
Published: December 2022

Background

Gram negative rod (GNR) bloodstream infections in patients requiring ICU level of care are associated with high risk of mortality. Very limited data is available on specific risk factors that are associated with this high mortality. The purpose of this study was to identify characteristics associated with mortality in ICU patients who were diagnosed with GNR bacteremia.

Methods

This was an IRB approved retrospective chart review that was conducted during November 2019 to November 2021 at a three hospital health system in NJ. Patients were included if they required ICU level of care, age ≥ 18 years old and had documented gram negative bacteremia. Patients were excluded if they had metastatic cancer, left against medical advice, or the blood culture was determined to be a contaminant. The primary endpoint of the study was to evaluate the association of characteristics and risk factors with all-cause inpatient mortality (ACIM) in patients with GNR bacteremia requiring ICU level of care. Secondary endpoints included impact of time to appropriate therapy and time to microbiologic cure on ACIM.

Results

There was a total of 79 patients who met inclusion criteria. The median age of patients was 69 years, 44% of the patients were female, and 81% of patients were in septic shock upon presentation to the ICU. The most common source of GNR bacteremia was urinary tract, followed by lower respiratory tract. The most common causative organism of bacteremia was E.coli, causing 25% of the cases. When evaluating primary endpoint, higher CCI (OR = 1.79, 95% CI [1.09-2.94]), and Pitt Bacteremia (OR = 2.1, 95% CI [1.32-3.35]) scores were independently associated with an increased risk of mortality in patients with gram-negative bacteremia in the ICU setting. Microbiologic cure was associated with a lower risk of mortality (OR=0.02, 95% CI [0.002-0.2]). Longer time to appropriate therapy and microbiologic cure were not associated with increased ACIM.

Results

Enterobacterales Breakdown

Conclusion

Patients admitted with GNR bacteremia requiring ICU level of care with higher CCI and Pitt Bacteremia scores have higher likelihood of suffering from ACIM. Microbiologic cure was independently associated with lower risk of ACIM. In a subset of patients, longer time to appropriate therapy and microbiologic cure was not associated with increased ACIM.

Disclosures

All Authors: No reported disclosures.
1842. Intravenous to Oral Antibiotic Stepdown for Uncomplicated Streptococcal Bacteremia
Authors: Salam Madison E , Lew Alison K , Nguyen Cynthia T , Pettit Natasha N , Pisano Jennifer
Published: December 2022

Background

Historically, intravenous (IV) antibiotics have been the standard of care for the treatment of bloodstream infections (BSIs). IV antibiotic use predisposes patients to line-related complications and is associated with increased length of stay (LOS) and treatment costs as compared to oral (PO) antibiotics. The purpose of this study was to compare the efficacy and safety of IV therapy versus PO stepdown for uncomplicated Streptococcal BSIs.

Methods

This single-center, retrospective, non-inferiority study included adults who had Streptoccoccus spp. in blood cultures with susceptibilities reported, < 48 hours of positive blood cultures, and were treated for the BSI. Patients were excluded if they had polymicrobial bacteremia, mortality prior to treatment completion, unattainable source control, or a complicated infection. The primary outcome was clinical success, defined as absence of infection recurrence, infection-related readmission, and infection-related mortality at 90 days. Secondary outcomes included individual components of composite endpoint, microbiological success, LOS, IV-line associated complications, and antibiotic-associated adverse events.

Results

Of 79 patients included, 36 patients (45.6%) received IV for the full course of therapy and 43 (54.4%) received PO stepdown. Baseline characteristics were similar between groups. The most common sources were skin and soft tissue (34.6%) and oropharyngeal (13.6%). The median duration of IV therapy in PO stepdown patients was 4.4 days (IQR 2.7 – 6.9). Amoxicillin/clavulanate (44%) and cefdinir (24%) were the most common PO agents. Clinical success occurred in 94% of IV only patients and 91% of PO stepdown patients (p = 0.573). No infection-related deaths or recurrences occurred. Line complications were more frequent in patients receiving IV compared to PO stepdown therapy (14% vs. 0%, p = 0.015). LOS was lower in the PO stepdown group (11 vs. 6 days, p < 0.001).

Conclusion

This study strengthens the hypothesis that PO stepdown therapy may be non-inferior to IV therapy for clinical success with a trend towards decreased LOS and line complications. However, this study was not powered to meet statistical significance. We are collaborating with several other centers to determine the true impact of this intervention.

Disclosures

All Authors: No reported disclosures.
1867. Characteristics and Outcomes of Patients with SARS-CoV-2 Reinfections Requiring Treatment in a COVID-19 Ambulatory Treatment Program
Authors: Cowman Kelsie , Golia Austin , Guo Yi , McSweeney Terrence D , Chang Mei H , Bao Hongkai , Nori Priya
Published: December 2022

Background

Montefiore Medical Center (MMC), Bronx, NY, established an ambulatory program to offer COVID-19 treatments (monoclonal antibodies [mAB] and oral antivirals) to patients with mild-moderate illness according to emergency use authorization criteria. Given multiple pandemic waves in the area, several patients have been reinfected and were treated twice. The objective of this analysis is to identify clinical characteristics and outcomes in patients with repeated COVID-19 infections and treatments.

Methods

Electronic health records were reviewed to identify patients between December 1, 2020 and April 28, 2022 who received COVID-19 treatment on more than one occasion at MMC. Data collected included demographics, risk factors for progression to severe illness, name and date of COVID-19 treatments received, vaccination status, and clinical outcomes of 30-day emergency department (ED) presentation or hospital admission following each treatment.

Results

Out of 3,042 total treated patients, 13 (0.4%) received multiple treatments with either mAB or oral antivirals for COVID-19 reinfection during the study period. Median age of reinfected patients requiring treatment was 50 years. Median days between first and second treatments was 298 days (range 91-468 days). The most common risk factor for progression to severe disease were cardiovascular disease (54%) and immunocompromised status (62%) (Table 1). Ten patients had received at least two doses of vaccine (77%) with Pfizer (54%) or Moderna (23%) vaccines prior to reinfection. No patients reported any adverse reactions to either treatment. Four patients presented to the ED or were hospitalized following treatment of reinfection, three of which were for COVID-related symptoms. Of these, two had two risk factors for progression and the third had been hospitalized previously for initial COVID-19 infection.

Conclusion

Though COVID-19 reinfection has been described, especially during Omicron surges, there were relatively few reinfected patients requiring treatment in our cohort. Patients with risk factors for disease progression may also be at increased risk for reinfection, especially the immunocompromised.

Disclosures

Kelsie Cowman, MPH, Merck: Grant/Research Support Yi Guo, PharmD, BCIDP, Merck: Grant/Research Support.
2322. Effectiveness of Recombinant Influenza Vaccine vs. Standard Dose Inactivated Influenza Vaccines Against Hospitalized Influenza-Related Outcomes in Adults: A Cluster Randomized Trial
Authors: Hsiao Amber , Yee Arnold , Fireman Bruce , Hansen John R , Lewis Ned , Klein Nicola P
Published: December 2022

Background

More effective influenza vaccines are needed to prevent influenza and its complications. Recombinant influenza vaccines may offer better protection than traditional egg-based vaccines. Using a cluster randomized design to estimate the relative vaccine effectiveness (rVE) of Flublok Quadrivalent recombinant influenza vaccine (RIV4) vs. standard dose inactivated influenza vaccine (SD-IIV4), we separately reported that RIV4 provided significantly better protection against primary outcome of confirmed influenza in adults 50–64 yrs in the 2018–20 moderately severe influenza seasons. Here we report the rVE against the secondary and exploratory outcomes of hospitalized influenza-related outcomes.

Methods

We randomized 66 facilities within Kaiser Permanente Northern California (KPNC) to routinely administer RIV4 or SD-IIV4 to adults, alternating vaccine formulations weekly by facility during the influenza season (ClinicalTrials.gov NCT03694392). Hospitalized cases of PCR-confirmed influenza, community-acquired pneumonia, and cardio-respiratory events were prespecified as secondary in 50–64 yrs and exploratory in 18–49 yrs. We estimated the relative hazard ratio (rHR) using Cox regression on a calendar timeline, adjusting for age, sex, and race, using facility-specific stabilized propensity scores. We calculated rVE as (1–rHR) x 100%.

Results

During the 2018–19 and 2019–20 seasons, the study consisted of 1,630,328 vaccinees 18–64 yrs (RIV4=632,962; SD-IIV4=997,366), and included 95 hospitalized influenza cases after RIV4 and 153 after SD-IIV4 among 50–64 yrs (Table 1). RIV4 vs. SD-IIV4 was not significantly more protective against hospitalized influenza-related outcomes in adults 50–64 yrs or 18–49 yrs.

Conclusion

While this large cluster randomized study found that RIV4 vs. SD-IIV4 reduced the risk of lab-confirmed influenza in adults 50–64 yrs across 2 influenza seasons, RIV4 and SD-IIV4 performed similarly against hospitalized influenza-related outcomes. Evaluating influenza-related hospitalizations during influenza seasons when more hospital outcomes occur may help to better understand the relative effectiveness of recombinant versus standard inactivated influenza vaccines against severe disease.

Disclosures

All Authors: No reported disclosures.
1915. Divided on dividers: Real-world assessment of the efficacy of barriers for prevention of aerosol exposure
Authors: Cadnum Jennifer , Jencson Annette , Memic Samir , Donskey Curtis
Published: December 2022

Background

Barriers are commonly installed in workplace situations where physical distancing cannot be maintained to reduce the risk for transmission of respiratory viruses. Although some types of barriers have been shown to reduce exposure to aerosols in laboratory-based testing, limited information is available on the efficacy of barriers in real-world settings.

Methods

In an acute care hospital, we tested the effectiveness of in-use plexiglass dividers in reducing exposure of staff to aerosolized particles. An aerosol sprayer was used to release 5% NaCl aerosol at 1 or 2 meters from staff members with and without the barrier positioned between the point of aerosol release and the hospital staff. Particle counts on the staff side of the barrier were measured using a 6-channel particle counter. A condensed moisture (fog) generating device was used to visualize the airflow patterns.

Results

Of 13 dividers tested, 6 (46%) significantly reduced peak aerosol particle counts detected behind the divider, 6 (46%) reduced peak particle counts only to modest non-significant degree, and 1 (8%) significantly increased particle counts behind the divider; the figure shows data for 3 dividers that illustrate the 3 types of results. For effective dividers, condensed moisture fog flowed around the divider toward outlet air vents positioned in the ceiling, whereas fog pooled immediately behind the divider that increased staff exposure before exiting in an outlet air vent positioned on the side wall.

Effective divider reducing staff aerosol exposure

Ineffective divider increasing staff aerosol exposure

Minimally effective divider

Conclusion

In real-world settings, plexiglass barriers vary widely in effectiveness in reducing staff exposure to aerosols, and some barriers may increase risk for exposure. Devices that visualize airflow patterns may be useful as simple tools to assess barriers.

Disclosures

All Authors: No reported disclosures.
1935. Cardiac Tamponade Following COVID-19 Vaccination
Authors: Murphy Christopher B , Kasule Sabirah N , Vikram Holenarasipur R
Published: December 2022

Background

While numerous, most described cases of myocarditis and pericarditis following COVID-19 vaccination are mild and self-limited. We present two cases of life-threatening cardiac tamponade following COVID-19 vaccination.

Methods

Two cases of cardiac tamponade in temporal association with COVID-19 vaccination were reviewed

Results

Case 1 : 75-year-old male with rheumatoid arthritis admitted with chest pressure and hypotension 2 days after his 1st dose of Pfizer-BioNTech COVID-19 vaccine. Pericardiocentesis removed 275 ml of exudative effusion with 14,140 nucleated cells/ml. Fluid bacterial and fungal cultures were negative; cytology was inconsistent with malignancy. He had no Epstein-Barr virus (EBV) or cytomegalovirus (CMV) viremia. Symptoms resolved on prednisone and colchicine. A week later, he had an uneventful second COVID-19 vaccine. He went on to have 3 recurrences of pericarditis starting two months after his first. One was within 48 hours of his COVID-19 booster. He is on long term prednisone. Case 2: 66-year-old male with non-Hodgkin’s lymphoma in remission. He developed chest pain a day after his 2nd dose of Pfizer-BioNTech COVID-19 vaccine. Admitted 4 days later with pericardial effusion and managed medically. Readmitted a week later with fever and chest pain. Echocardiogram now showed cardiac tamponade. Pericardiocentesis removed 400 ml of exudative fluid with 1,191 nucleated cells/mL. Cultures for bacteria, fungi, and mycobacteria were negative. Cytology didn't show malignancy. Serologies for CMV, EBV and parvovirus represented past infection. He was discharged with a pericardial drain, colchicine, and NSAIDs. He was later readmitted with fevers. Echocardiogram only showed small pericardial effusion, which did not require drainage. Figure 1Circumferential pericardial effusion seen on trans-thoracic echocardiography from patient in case 1.

Conclusion

Given the proximity to COVID-19 vaccination and lack of alternative explanations, we believe that tamponade was a direct result of post-vaccine inflammatory pericarditis. Neither patient had a prior history of pericardial effusion. Both tested negative for SARS-CoV-2 by nasopharyngeal swab excluding active infection. Healthcare providers should consider the possibility of pericardial effusion and tamponade in patients with chest pain, shortness of breath, or hypotension following COVID-19 vaccination.

Disclosures

All Authors: No reported disclosures.
2012. A Descriptive Study of Infections Complicating Extracorporeal Membrane Oxygenations in Trauma Patients
Authors: Schweickhardt Samantha K , Sams Valerie , Radowsky Jason , Marcus Joseph E , Sobieszczyk Michal J
Published: December 2022

Background

Extracorporeal Membrane Oxygenation (ECMO) is a growing modality for respiratory and circulatory support in patients with traumatic injuries. There is limited data on the pathogens complicating a trauma patient’s ECMO course and thus empiric antibiotic choices are difficult in this cohort. We report the incidence and infection type in trauma patients receiving ECMO to potentially guide future empiric antibiotic treatment and improve outcomes.

Methods

A descriptive chart review was performed on all trauma patients at Brooke Army Medical Center receiving ECMO between February 2013 and July 2021. Charts were reviewed to identify pathogens by culture site as well as time to infection following cannulation. This protocol was approved by the 59th Medical Wing Institutional Review Board.

Results

Twenty-one trauma patients underwent ECMO during the study period. The majority of patients were men (n=19, 90%) with a median age of 30 years [IQR 27-38] with a median ECMO run of 227 hours [IQR 93-338]. Motor vehicle crashes (17, 81%) accounted for the majority of injuries, with gunshot wounds (2, 10%), blast injuries (1, 5%) and falls (1, 5%) accounting for the remainder. 16 (76%) patients survived to discharge, and infection was not associated with mortality (p=0.11). Of the 24 infections, the majority were respiratory (13, 58/1000 ECMO days) followed by skin and soft tissue (6, 26/1000 ECMO days), blood stream (4, 18/1000 ECMO days), and urinary tract (1, 5/1000 ECMO days). Gram-negatives were the most commonly isolated organism from all sites (Table 1) and at all time periods after cannulation (Table 2). Multi-drug resistant organisms accounted for 32% (n=9) of infections and were independent of time from cannulation.

Conclusion

This is the first study to describe infections in trauma patients requiring ECMO support. We observed majority Gram-negative infections regardless of culture site or time after cannulation. Determining empiric antibiotics will require a larger study of patients to identify trends in pathogens and ultimately improve antimicrobial stewardship in this unique population.

Disclosures

All Authors: No reported disclosures.
2024. Human Factor Considerations in Support of a Flexible IV Connector Safeguard to Prevent Central Line Associated Blood Stream Infections (CLABSI)
Authors: Walterspiel Juan N
Published: December 2022

Background

One of the sources of central line infections is contaminated and poorly disinfected IV connectors(CON).

A recent study found 23% of IV-line CONs were contaminated with bacteria, despite strict infection control guidelines that include the use of alcohol-lined caps (ALC).

Contamination (CONT) occurs after protective ALC has been removed in preparation for an infusion, and nurses perform their multiple tasks. These include purging air bubbles from the IV line, setting pumps, verifying medications, and keeping an eye on the patient. It is not surprising that nurses admitted that sterilization of IV CONs was not prior to 3% - 4% of infusions.

Schielded IV connector

Methods

A flexible rounded shield extending above a standard needleless CON to protect it from CONT was designed and tested (Pat pend).

A total of 4, 2 ICU Medical Inc. needleless CONs, one shielded and one unshielded, and two Komashine Inc. CONs, also one shielded and one unshielded were disinfected with 70% alcohol and their lines taped to the abdomen of 2 volunteers wearing loose shirts over the connectors.

The CONs remained on the volunteers for 3 hours, in 2 sessions. All 16 CON ends were cultured on Columbia blood agar, and plates held 48 h. Readings were evaluated by statistical analysis of 16 predictions (coinflips).

Results

It was confirmed that the tested shielded CONs were easy to sterilize, connect to infusion lines and that there was ample space left to screw on and off alcohol caps.

Colonies were absent from the protected connector ends, whereas all the unshielded ends grew several colonies.

The probability of observing the projected efficacy results, 8 unshielded with subsequent bacterial growth, and eight shielded, remaining sterile, i.e. not growing bacteria is < 0.00002.

The lack of contamination on the shielded ends proved that the air currents generated by the movements of the volunteers, between their skin and their skirts did not transport bacteria to the shielded connector ends.

Conclusion

A properly designed flexible contamination shield will prevent the proportion of line infections that are caused by human factors. Pls, submit severe adverse event reports (prolongation of hospitalization or death) caused by contemporary "defective" IV connectors to the FDA to change their faulty design.

Disclosures

All Authors: No reported disclosures.
2115. Long Term Follow-up and Correlates of Success in Patients on Immune Globulin for Antibody Deficiency
Authors: Duffield Olivia , Axelrod Peter
Published: December 2022

Background

Antibody deficiencies range from mild deficits of antibody subclasses to more severe deficiencies of all immune globulins. Patients with deficiencies of immune globulin G (IgG) are predisposed to recurrent sinopulmonary infections, often necessitating multiple courses of antibiotics and frequent hospitalizations and provider visits. Treatment with intravenous immune globulin (IVIG) replacement therapy is currently indicated for patients with severe primary immune deficiencies but is less well studied in patients with more mild deficits that nonetheless experience recurrent infections.

Methods

A retrospective chart review was conducted on 71 patients from the Temple University Infectious Disease Department (15 transplant recipients) with varying levels of antibody deficiency that had been treated with monthly IVIG for at least six months. Available patients (N=49) were interviewed by phone about their experiences on IVIG, side effects, and quality of life changes on therapy.

Results

Mean age sx onset was 40 y,68% were women, 87% Caucasian, 49% had pneumonia, 65% purulent bronchitis, 65% sinusitis. Patients reported a mean reduction in infection frequency of 78% and average patient-reported improvement in quality of life was 4.7/5.0. Antibody deficiency levels at baseline were not correlated with infection reduction (R=-.05, p=0.71), Figure 1 and neither was response to pneumococcal polysaccharide vaccine (vaccine responder median infection reduction 83%; non responder 87%, p= 0.60) Figure 2. Adverse events on treatment were experienced by 59% of patients and caused 9 patients (13%) to stop treatment. There was no difference in incidence of adverse events between men and women (p= 0.076), but women had a 50% higher rates of severe headache than men (p= 0.038); 10% pts required a port or PICC, 32% IV fluids, 48% IV steroids, 31% IVIG brand change; 17% changed to subcutaneous IG. Figure 1:Pre-treatment Antibody Deficit and Infection Reduction by IVIGPlot of percent deficit of most deficient antibody subclass against infection reduction by IVIG (% of yearly pre-IVIG infections)Infection Reduction by IVIG According to Vaccine Responsiveness

Box plot of percent infection reduction after IVIG according to response to polysaccharide vaccine

Conclusion

Even patients with relatively mild immunoglobulin deficiencies can experience a significant reduction in recurrent infections and improved quality of life when treated with immunoglobulin. IVIG is usually well tolerated for many years but may require adjunctive steroids, IV hydration, or brand change to limit adverse side effects.

Disclosures

All Authors: No reported disclosures.
2123. The Impact of Staphylococcus aureus Peri-transplant Cultures on Six-Month Outcomes in Lung Transplantation
Authors: Harris Courtney E , Mehta Abhinav , Kim Andy J , Goldberg Hilary J , Mallidi Hari R , Mallidi Hari R , Townsend Keri , Coppolino Antonio , Thaniyavarn Tany , Kennedy John C , Lee Stefi F , Durney Valerie , Marshall Shirley , Fenty-Scotland Jessica , Cosimi Lisa A , Kovac Victor , Issa Nicolas C , Sharma Nirmal S , Baden Lindsey R , Woolley Ann E
Published: December 2022

Background

Staphylococcus aureus (S. aureus) infections post-lung transplant lead to increased mortality. The impact of S. aureus peri-transplant respiratory cultures on post-transplant outcomes is unknown as is the optimal duration of peri-transplant antibiotics. We compared lung transplant recipients with and without S. aureus growth on peri-transplant cultures and the impact on 6-month outcomes including rejection, survival, and occurrence of S. aureus infections.

Methods

A single-center, retrospective study of lung transplant recipients between January 2017 and April 2021 was performed. Donor/recipient characteristics, microbiologic data, antibiotics, and 6-month outcomes were analyzed.

Results

In this 4.5-year study period, 229 patients underwent lung transplant. 121 (53%) had S. aureus growth on peri-transplant cultures, of which 84 (69%) were methicillin-susceptible (MSSA), 30 (25%) methicillin-resistant (MRSA), and 7 (6%) had MSSA and MRSA. Median duration of antibiotics post-transplant was 28-days in the S. aureus group. 67% of non-S. aureus recipients received S. aureus targeting antibiotics (p = < 0.001) for other indications for a median of 13-days. In the S. aureus cohort, donors were younger (median age 33 vs 38 years, p = 0.027) and more donors died from drug intoxication (50% vs 31%, p = 0.005) [Table 1]. Recipient baseline characteristics and median length of hospitalization were similar in both cohorts. There were no statistically significant differences in 6-month outcomes, including rates of rejection or survival [Figure 1]. Having grown S. aureus in peri-transplant cultures was not associated with a higher incidence of post-transplant S. aureus infections (10% vs 13%, p = 0.534). Patients who had a S. aureus infection post-transplant had lower 6-month survival that was not statistically significant (85% vs 93%, p = 0.131).

Conclusion

The growth of S. aureus on peri-transplant respiratory cultures with a median 4-week antibiotic course does not increase the risk of having a S. aureus infection post-transplant and is not associated with increased mortality or rejection at 6-months. The impact of a shorter duration of peri-transplant antibiotics on recurrence of infection and outcomes needs to be further studied.

Disclosures

Nicolas C. Issa, MD, AiCuris: Grant/Research Support|Merck: Grant/Research Support.
2141. Investigating a (Natural) Killer by Studying the Victims: Searching for Mechanisms to Selectively Inhibit NK-cell Immunosuppressive Function to Improve Vaccine Responses
Authors: Cox Andrew , Waggoner Stephen N , Katko Alexander , Roskin Krishna
Published: December 2022

Background

Decades of effort have yet to deliver an efficacious vaccine for pathogens such as HIV, despite major revelations about HIV antigens and development of new vaccine platforms. Innovative outside-the-box approaches are needed to overcome immunological roadblocks to the success of past and current vaccine regimens. We discovered that natural killer (NK) cells are a potent obstacle to vaccine success through perforin-dependent suppression of activated CD4 T cell responses early after vaccination. This killing reduces the quantity and quality of antibody responses. Yet, the features of NK cells that enable this activity or determine susceptibility of specific subsets of T cells remain ill-defined.

Methods

We used transgenic virus-specific mouse CD4 T cells to detect very early changes in responding T cells immediately proximal to immunoregulatory killing by NK cells. Transgenic T cells were seeded in recipient mice, depleted or not of NK cells, and then infected with lymphocytic choriomeningitis virus. At early time points post-infection, these T cells were isolated for single-cell RNA-sequencing or high-dimensional flow cytometry analyses. These data revealed transcriptomic and proteomic features of subsets of activated CD4 T cells whose presence was enabled or enhanced by the absence of NK cells.

Results

Perforin-dependent killing of CD4 T cells by NK cells is measurable on days 2 and 3 post-infection. Analysis of the pool of responding T cells on day 3 revealed phenotypic skewing away from follicular helper T cell-type responses to Th1-type responses in the presence of NK cells. Single cell RNA sequencing and high-dimensional spectral flow cytometry reveal clusters of T cells that are markedly enriched in the absence of NK cells.

Conclusion

We created a model system permitting characterization of the population of T cells targeted by NK cells after infection or immunization. Elucidation of features of the targeted T cells will provide mechanistic insights in the receptor-ligand system enabling this biology, improve our understanding of how NK cells influence the pool of responding T cells, and facilitate discovery of the corresponding subset of NK cells responsible for this activity. These discoveries are likely to facilitate development of methods to enhance vaccine responses.

Disclosures

All Authors: No reported disclosures.