bluuebunny/crossref_metadata_2025 huggingface dataset:
1821. Clinical Characteristics of Staphylococcus aureus Bacteremia with the Skip Phenomenon: a Case Control Study.
Authors: Tsuchido Yasuhiro , Shinohara Koh , Yukawa Satomi , Noguchi Taro , Yamamoto Masaki , Matsumura Yasufumi , Nagao Miki
Published: December 2022

Background

Staphylococcus aureus bacteremia (SAB) is one of the most common causes of persistent bacteremia, which is associated with complicated disease and poor clinical outcome. “The skip phenomenon (SP)” was recently proposed concept which might exhibit fluctuating blood culture positivity, but its clinical significance remained to be clarified. The aim of the study was to evaluate the clinical characteristics of SAB with the SP.

Methods

This is a retrospective case-control study conducted at 1141-bed university hospital during 2006-2021. Adult inpatients with more than 3 days of SAB were included. Cases were patients with SP, and controls were the rest of the patients. Duration of bacteremia was defined as bacteremic days under active antibiotic therapy counting the first day as day 1. SP was defined as at least 1 day of negative blood cultures following documented S. aureus bacteremia and preceding recurrence of a positive blood culture, which was taken within 14 days from last positive culture. Patient characteristics including medical comorbidity, implanted hardware, and focus of infection were reviewed.

Results

Of the 149 patients, 17 (11.4%) had the SP. A total of 20 skip phenomenon episodes among 17 cases were observed. Three patients had 2 episodes of SP. Of the 20 episodes of the SP, 7 (35.0 %) were confirmed with single set, and 13 (65.0 %) were confirmed with 2 sets of negative blood culture. The median interval from first positive blood culture to first SP episode in each case was 7 days (interquartile range [IQR], 6-16 days). Of 20 episodes of SP, 18 (90.0 %) were accompanied with fever as an indication for taking blood culture. The cases (n=17) were more likely than controls (n=132) to have a longer duration of bacteremia (median [IQR], 14 [11–36] days, vs 4 [3–7] days; p < 0.001), and diabetes mellitus (52.9 % vs 25.0 %, p=0.023). There was no significant difference in deep-seated infection (64.7 % vs 48.5 %, p=0.303), methicillin resistance rate (76.5 % vs 50.0 %, p=0.068), and 90-day mortality (17.6 % vs 27.3 %, p=0.561) between cases and controls.

Conclusion

Our findings suggest that we should consider to take blood culture repeatedly when clinically indicated, even if we confirmed the negativity once before.

Disclosures

All Authors: No reported disclosures.
1822. Clinical Outcomes Associated with Oral Beta-Lactam Therapy versus Oral Fluoroquinolones/TMP-SMX for Uncomplicated Gram-Negative Bacteremia
Authors: Kaur Satwinder S , Babic Jessica T , Nguyen Steven , Patel Shivani
Published: December 2022

Background

Agents commonly used as oral step-down therapy in Enterobacterales bacteremia include fluoroquinolones and TMP-SMX. The use of these oral agents have been associated with adverse events. Oral β-lactams are not recommended to treat Enterobacterales bacteremia because of concerns for sub-therapeutic serum concentrations. Given the limited data on clinical effectiveness of oral β-lactams and increased limitations with fluoroquinolones and TMP-SMX, oral β-lactams may be an alternative option. The purpose of this study is to evaluate the clinical effectiveness in patients transitioned to oral β-lactams versus fluoroquinolones or TMP-SMX for the step-down treatment of uncomplicated Enterobacterales bacteremia.

Methods

A multi-center, retrospective, propensity-score matched, observational cohort study was conducted from July 1, 2017 to December 31, 2020, at 11 Memorial Hermann Health System hospitals among 690 patients with uncomplicated Enterobacterales bacteremia. Patients were included if they received > 1 day of intravenous antibiotic therapy followed by definitive oral step-down therapy with a β-lactam, fluoroquinolone, or TMP-SMX. The primary outcome was treatment failure within 30 days of starting oral antibiotics, defined as at least one of the following: recurrent bacteremia, transition to IV antibiotics, new-onset sepsis, 30-day readmission, or 30-day all-cause mortality.

Results

After the patients were propensity score matched 1:1, a total of 199 patients with uncomplicated Enterobacterales bacteremia were included in each group. Treatment failure occurred in 8 patients (4%) who received β-lactams and 10 patients (5%) who received fluoroquinolones or TMP-SMX (OR, 0.79 [95% CI, 0.306-2.04] p-value 0.629). Median length of hospital stay was 5 days for both groups (p-value 0.911), and median duration of oral antibiotics was 10 days in the fluoroquinolone or TMP-SMX group and 11 days in the β-lactam group (p-value 0.377).

Conclusion

Based on the results of this study, no significant difference in treatment failure was seen in patients who were transitioned to β-lactams versus fluoroquinolones or TMP-SMX as oral step-down therapy for uncomplicated Enterobacterales bacteremia. Oral β-lactams appear to be a safe and effective option.

Disclosures

All Authors: No reported disclosures.
1824. Combination therapy of daptomycin/colistin for extreme drug resistant Acinetobacter baumannii bacteremia
Authors: Lampada Charis , Kourti Maria , Charisi Konstantina , Iosifidis Elias , Zarras Charalambos , Roilides Emmanuel , Antachopoulos Charalambos
Published: December 2022

Background

There are experimental data demonstrating synergistic in-vitro activity of colistin and daptomycin against extremely drug-resistant (XDR) strains of Acinetobacter baumannii.Aim of this study is the description of a case-series of patients with confirmed XDR A. baumannii bloodstream infection (BSI) receiving an antimicrobial regimen including colistin and daptomycin.

Methods

Prospective study of patients with BSI caused by XDR A. baumannii from May 2021 to February 2022 in a tertiary level hospital. Demographic, clinical and laboratory data were recorded and evaluated from all patients. BacT Alert system (BiomerieuxR) was used for blood cultures and bacterial identification and susceptibility testing was performed using VITEK® 2. Colistin susceptibility testing (dilution method) were interpreted in accordance to Clinical and Laboratory Standards Institute (CLSI) criteria.

Results

A total of 16 episodes of XDR A. baumannii were recorded in 16 patients (14 males). Median age was 60 (range 38-85) years. Ten patients (56.2%) were hospitalized in medical wards, and 43.8% in surgery wards. One-third of patients had previously been admitted to the Intensive Care Unit, while all patients had an indwelling central vascular catheter. Fourteen of the 16 XDR strains of A. baumannii were also resistant to colistin. Also, 2 of the 16 strains had a MIC of 2μg/ml for tigecycline, while in the remaining 14 the MIC was > 2μg/ml. All isolates had meropenem MIC >16μg/ml. All patients received a combination of colistin -daptomycin -meropenem -tigecycline. Clinical and laboratory improvement was noted in 15 of the 16 patients within the 14 days of treatment. Fifteen out of the 16 patients showed a microbiological response: the mean duration between the start of treatment and the first negative blood culture was 12 days.Finally, no patient experienced a marked increase in CPK due to daptomycin use.

Conclusion

The outcome of this case series of patients receiving colistin-daptomycin combination as part of a broader synergistic antimicrobial regimen to treat XDR A. baumannii was satisfactory, with no significant adverse reactions. This potential clinical benefit of the colistin/daptomycin combination should be further evaluated in a larger comparative study.

Disclosures

All Authors: No reported disclosures.
2314. Hospitalizations and Antibiotic Use in the Year Prior to an Incident C. difficile Infection for Medicare Beneficiaries in Four States, 2016–2018
Authors: Hatfield Kelly M , Baggs James , Reddy Sujan , Aranmolate Rasaki , Meek James , Fridkin Scott , Szydlowski Jill , Hatwar Trupti T , Dumyati Ghinwa , Watkins Jasmine , Wilson Christopher , Clifford McDonald L , Jernigan John A , Guh Alice
Published: December 2022

Background

Studies describing risk factors for Clostridioides difficile infection (CDI) are often limited in their ability to identify potentially important exposures occurring long before diagnosis. We describe hospitalizations and antibiotic use (AU) occurring up to one year prior to CDI diagnosis among Medicare beneficiaries.

Methods

We studied incident CDI cases (positive C. difficile test in a person ≥65 years without a positive test in the prior 8 weeks) identified during 2016–2018 through population-based CDI surveillance from four states participating in the Centers for Disease Control and Prevention’s Emerging Infections Program. The analysis included specimens collected in all settings and was limited to case patients who were identified as having fee-for-service Medicare and Part D drug coverage for the year preceding specimen collection. Inpatient hospitalization data was extracted from Medicare Provider Analysis and Review (MEDPAR) files and outpatient AU (prescriptions filled) was determined using Part D drug event files. Timing of hospitalizations and antibiotic prescriptions were described as recent (0–3 months prior to specimen collection) or remote (4–12 months prior).

Results

Of 1,953 CDI cases, 1,594 (82%) filled ≥1 course of outpatient antibiotics in the prior year; 805 (41%) filled an antibiotic both recently and remotely, 497 (25%) only remotely, and 292 (15%) only recently.

Cases with outpatient AU received a median of 23.5 (IQR 12–46) total days supplied, and a median of 2 different antibiotic classes (IQR 1 – 3). The most frequent antibiotic classes filled include fluoroquinolones (17% of all antibiotics filled), 1st generation cephalosporins (10%), and folate pathway inhibitors (10%).

Overall, 1,314 (67%) cases were hospitalized in the prior year; 569 (29%) were hospitalized both recently and remotely, 446 (23%) only recently, and 299 (15%) only remotely. Median length of stay was 13 days (IQR 6–28).

A total of 142 cases (7%) did not have hospitalization or outpatient AU in the prior year, and 1,097 (56%) had both.

Conclusion

Incident CDI cases have substantial exposure to recent and remote hospitalization and outpatient AU. Understanding cumulative effects of multiple risk factors can guide prevention strategies, including antibiotic stewardship efforts.

Disclosures

Scott Fridkin, MD, Pfizer: Grant/Research Support Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.
1835. Evaluation of Predicting Performance of POSITIVE, PREDICT and VIRSTA Score for Infective Endocarditis in Patients with Staphylococcus aureus Bacteremia
Authors: Pinargote Paulette , Salazar Wilmer , Katubbadi Ayeesha , Patel Neev , Alam Mohammad , Bhuiyan Mohammad , Vanchiere John
Published: December 2022

Background

Prompt identification of Infective Endocarditis (IE) in patients with Staphylococcus aureus bacteremia (SAB) is important as delayed diagnosis results in 15-20% increased mortality. Predictive clinical scoring strategies have been developed to optimize the diagnostic process, particularly the use of invasive methods such as Transesophageal Echocardiography(TEE), known to be superior to Transthoracic Echocardiography but is not suitable for all patients. Three scoring systems have been proposed to predict the risk of IE: VIRSTA, PREDICT and POSITIVE. We compared these scoring strategies in combination with other clinical data to test the hypothesis that inclusion of time to blood culture positivity(TTP) in the scoring strategies might improve the sensitivity and specificity of clinical risk stratification.

Methods

Adults (≥ 18y) with SAB admitted to Ochsner LSU Health Shreveport in 2020-2021 were retrospectively screened. Patients with polymicrobial bacteremia, with index blood cultures obtained at a different institution and without cardiac imaging were excluded. In this preliminary analysis, 60 patients (30 with and without IE) were studied. IE was defined as patients who met modified Dukes criteria for definite IE. The three scores were calculated for each subject. TTP, defined as the time from incubation to automated detection, was obtained from the microbiology laboratory. Clinical predictors of IE were identified using multivariable logistic regression analysis.

Results

The demographic, baseline characteristics and mode of presentation, was no different in both groups based on analysis of >50 factors. The mean TTP for subjects with and without IE were no different (9.65h vs 11h, p=0.12) TTP≤13h as an independent variable was found to be sensitive but not specific. VIRSTA was found to be the most sensitive scoring method. POSITIVE, which includes TTP as a component, was the most accurate, but least sensitive method. Addition of TTP≤13h to VIRSTA and PREDICT increased sensitivity but lowered specificity.

Conclusion

While the sensitivity of scoring strategies is acceptable, none of the proposed methods has adequate specificity. Larger studies are needed for the development of a highly specific and accurate scoring method that includes classic risk factors and TTP.

Disclosures

All Authors: No reported disclosures.
1843. Intravenous versus Partial Oral Antibiotic Therapy in the Treatment of Uncomplicated Bloodstream Infection due to Streptococcus species
Authors: Broermann Lynn , Al-Hasan Majdi N , Al-Hasan Majdi N , Withers Sarah , Benbow Kristina L , Ramsey Taylor , Ogren Katelyn , McTavish Meghan , Webster William , Winders Hana R
Published: December 2022

Background

Effectiveness of oral antibiotics for transition of therapy in uncomplicated bloodstream infections (BSI) due to Streptococcus species remains unclear. This retrospective cohort study examines effectiveness of partial oral antibiotic regimens in patients with uncomplicated BSI due to Streptococcus species compared to standard intravenous (IV) only therapy.

Methods

Adult patients with uncomplicated BSI due to Streptococcus species from April 2016 through June 2020 in 7 hospitals within Prisma Health in South Carolina were evaluated. Patients who died within 7 days of BSI were excluded to reduce the impact of survival bias. Multivariate Cox proportional hazards regression was used to examine time to treatment failure, defined as a composite of all-cause mortality and BSI recurrence within 90 days.

Results

A total of 222 patients with Streptococcus species BSI were included in the analysis. Overall, the median age was 62 years, and 116 (52.3%) were men. Beta-hemolytic streptococci (87; 39.2%) were the most common bloodstream isolates, followed by S. pneumoniae (76; 34.2%) and viridans group streptococci (59; 26.6%). Among this cohort, 99 patients received only IV antibiotics, and the remaining 123 received partial oral therapy. The median duration of therapy in both groups was 14 days, and median duration of IV antibiotics prior to oral transition was 4 days. Most patients in the partial oral group were transitioned to either oral beta-lactams (62; 50.4%) or fluoroquinolones (47; 38.2%). Of the IV only group, 46 (46.5%) required outpatient IV antibiotics. Treatment failure rates were 12.0% and 4.4% in the IV only and partial oral therapy groups, respectively (p=0.04). After adjustments for age, chronic comorbidities, and initial response to therapy within the first 72-96 hours, there was no difference in the risk of treatment failure in the partial oral compared to IV only group (hazards ratio 0.55, 95% CI 0.19-1.64; p=0.28).

Conclusion

Transitioning patients from IV to oral antibiotics may be a reasonable strategy in the management of uncomplicated BSI due to Streptococcus species. Partial oral therapy does not seem to have a higher treatment failure rate than standard IV only therapy and may spare many patients from outpatient IV antibiotics.

Disclosures

All Authors: No reported disclosures.
2316. Impact of Surveillance and Decolonization on Methicillin-resistant Staphylococcus aureus Infection Rates in a Neonatal Intensive Care Unit
Authors: Hiermandi Nahid , Foster Catherine , Purnell Krystal , Campbell Judith R , Marquez Lucila
Published: December 2022

Background

Neonates colonized with methicillin-resistant Staphylococcus aureus (MRSA) are at high risk of developing life-threatening MRSA infection. In neonatal intensive care units, surveillance for MRSA colonization and decolonization of positive infants aims to interrupt MRSA transmission and progression to infection.

Methods

In this retrospective study, we compared rates of MRSA infections before and after implementation of an MRSA surveillance and decolonization protocol in a 42-bed neonatal intensive care unit. Infections from Jan 2014 to Dec 2020 were reviewed. The protocol was introduced in late October 2016 and fully implemented by Feb 2017. MRSA colonization was initially assessed with cultures of three body sites and later the methodology was changed to PCR. Colonized infants were treated with topical mupirocin and 2% chlorhexidine gluconate wipes. MRSA infection was defined as any specimen from which MRSA was isolated. Multiple positive specimens from the same site were considered the same infection if within a 14-day window. Infection rates were calculated as unique infections per 1000 patient days. An interrupted time-series analysis was performed on Stata 14.2. This study was approved through the Baylor College of Medicine Institutional Review Board.

Results

While we continued to identify colonized infants in the unit, monthly infection rates in the post-intervention period never reached the peak rates in the pre-intervention period and clusters of infections have been eliminated (Figure 1). Prior to the intervention in Feb 2017, the rate of infection increased by 0.06 infections per 1000 patient days every month (p=0.124, CI = -0.017, 0.137). During the first month after full implementation of the intervention, the infection rate decreased by 1.522 infections per 1000 patient days (p=0.145, CI = -3.579, 0.534) followed by a monthly rate decrease of 0.066 infections per 1000 patient days (p=0.088, CI = -0.142, 0.010) (Figure 2).

Conclusion

We found a sustained trend towards decreased MRSA infections after implementing MRSA surveillance and decolonization. Further studies should explore adherence to decolonization, whether decolonization is enduring and what risk factors lead to recurrence of colonization.

Disclosures

All Authors: No reported disclosures.
1851. Recurrence of Streptococcus agalactiae Bacteremia - Risk Factors and Complications
Authors: Wang Taylor B , Zimilover Adam , Garellek Jonathan , Mahvish Gull , Parvez Hina , Given Hafsa No Name , Singh Damanbir , Patel Pranavkumar , Patel Pranavkumar , Gorlin Margaret , Kim Angela , Flannery Sarah , Epstein Marcia , Smith Miriam A
Published: December 2022

Background

The primary objective was to identify the frequency of recurrent Streptococcus agalactiae (GBS) bacteremia and associated risk factors for recurrence. The secondary objective was to determine the source of the initial GBS bacteremia and complications.

Methods

This was a retrospective observational study evaluating patients who were admitted to any of the 12 hospitals within the Northwell Health System from 1/1/2016 to 1/1/2020. Non-pregnant patients ≥ 18 years of age with GBS bacteremia were included. Recurrence was defined as admission due to GBS bacteremia within 1 year after a positive blood culture. Statistical methods performed include t-test or Wilcoxon Rank Sum test, Chi-square, Fisher exact tests, and both univariable and multivariable logistic regressions.

Results

390 patients met inclusion criteria with a median age of 63 years old. Majority were white (61.5%) and male (54.1%). Recurrence was found in 18 of 390 patients (4.62%). There was a significant increase in recurrence for patients allergic to penicillin or cephalosporins (p< 0.03), patients with implantable cardiac devices (ICDs) (p< 0.03) and patients who did not receive β-lactams and/or vancomycin as initial treatment (p< 0.05). 6 of the 18 patients were allergic to penicillin or cephalosporins. The estimated odds of recurrence in patients with ICDs were ∼5.4 times the odds of those without ICDs controlling for allergies (p< 0.04, 95% CI 1.7 – 20.0) or controlling for initial antimicrobial treatment (p< 0.04, 95% CI 1.5 – 18.7). The most common sources of GBS bacteremia were skin and soft tissue (35.1%), unknown (27.9%), and urinary tract (6.41%). Endocarditis was diagnosed in 8 patients (2.05%) via transesophageal echocardiogram. Other complications of GBS bacteremia included vertebral osteomyelitis (3.08%), epidural abscess (0.77%), and septic arthritis (0.77%). Median treatment duration was 15 days, with no significant difference in recurrence (p=0.75).

Conclusion

GBS bacteremia recurred in 4.62% of patients. Recurrence was significantly associated with ICDs, penicillin or cephalosporin allergies, and not receiving β-lactam and/or vancomycin-based regimens as initial therapy. The substantial rate of recurrent GBS bacteremia has important clinical implications.

Disclosures

All Authors: No reported disclosures.
1854. Response to an Intravenous versus Oral Antibiotic Regimen in Brucellosis Bacteremia: A Single-Center Experience
Authors: Nazir Imran , Almatrafi Mohammed A , Imran Iffat , Rahman Sayed , Abdullahi Hanan , Muddassir Rabia , Farouk Ahmad , Alsahaf Nouf , Maksood Lama , Ahmed Waleed
Published: December 2022

Background

Human brucellosis is an infectious multisystem disease that varies in severity and clinical course. Bacteremia in brucellosis is common; however, data on epidemiology and management of Brucella bacteremia are scarce. The World Health Organization recommends using doxycycline with rifampicin or an aminoglycoside for brucellosis. This study aims to compare the efficacy of the two treatment regimens (oral doxycycline/rifampicin or ciprofloxacin versus IV gentamicin plus oral doxycycline/rifampicin or ciprofloxacin) in Brucella bacteremia.

Methods

In this single-center, retrospective cohort study, we analyzed the outcomes of 93 adults with confirmed Brucella bacteremia from 2017 to 2020. The diagnosis of brucellosis was based on positive blood culture for Brucella species. The patients were divided into two cohorts according to the treatment regimen received (oral versus IV). Blood culture negativity after four weeks and clinical cure rate at end of therapy were the co-primary endpoints, while side effects were secondary endpoints. Fisher's exact test and Pearson's chi-square test were applied to compare the two groups. The data were analyzed using SPSS version 23. A P-value < .05 was considered significant.

Results

A total of 93 cases of Brucella bacteremia were enrolled, with 64 (68.8%) patients being male, and the group mean age being 44.3 ± 19.2 years. Overall, 37 (39.8%) patients received IV regimen, while 56 (60.2%) received oral treatment. Follow-up blood culture negativity after four weeks for both groups was 90.3% (n=84) with no difference between the oral and IV regimens (87.5% (n=49) versus 94.6% (n=37); P= .348, respectively). The overall clinical cure rate was 93.5% (n=87) for both groups combined, with no significant difference between the oral and IV groups (91% (n=51) versus 97.3% (n=36); P= .397, respectively). Transaminitis (7.1% vs. 5.4%), vomiting (5.4% vs. 8.1%), and acute kidney injury (0% vs. 2.7%) were all reported in the oral and IV groups, respectively, with no statistically significant difference between the two groups (P =.590). No deaths were reported over this period.

Conclusion

Oral and IV antimicrobial regimens have the same response rates in Brucella bacteremia patients.

Disclosures

All Authors: No reported disclosures.
2318. A Composite Peptide Vaccine Comprised of Conserved SARS-CoV-2 and Influenza Epitopes Generated Antisera Reponses to Both Coronavirus and Influenza
Authors: Rikhi Nimisha , Muema Kevin , Kroscher Kellie , Schuman Richard F , Assiaw-Dufu Aba , Sei Clara J , Fischer Gerald W
Published: December 2022

Background

While influenza and SARS-CoV-2 virus can be severe, co-infection with these viruses has the potential for worsening the clinical outcome. The combined infection of influenza A virus (IAV) and SARS-CoV-2 in animal models has also shown elevated SARS-CoV-2 viral load and pneumonia. Co-vaccination may provide a useful option in prevention of combined infection. In this study, a composite peptide vaccine comprised of highly conserved influenza neuraminidase (NA) and matrix protein (M2e) epitopes, in combination with either conserved spike protein (SP) or RNA polymerase (POL) epitopes of SARS-CoV-2 generated robust immune responses to both coronavirus and influenza virus.

Methods

Mice were immunized with 20µg of Coronavirus Pep02 (CorPep02, comprised of POL) or Coronavirus Pep05 (CorPep05, comprised of POL and NA+M2e) or Coronavirus Pep11 (CorPep11, comprised of SP and NA+M2e), formulated with AddaVax™. Serum antibody titers to both coronavirus and influenza peptides, and whole viruses were analyzed using ELISA. Antisera neutralizing activity against IAV was determined using microneutralization assay (MNA).

Results

CorPep05 immunization generated enhanced IgG1 and IgG2b antisera responses to the immunogens compared to CorPep02, starting at Day-21. Immunization with CorPep05 or CorPep11 induced strong IgG1 and IgG2b immune responses to the composite coronavirus peptides, influenza NA and M2e peptides, coronavirus POL and SP peptides. Antisera from CorPep05 and CorPep11 groups bound to both viruses (IAV and human coronavirus NL-63 (HCoV NL-63)) and demonstrated neutralizing activity against IAV, with titers >5000.

Conclusion

A composite peptide vaccine comprised of both influenza (NA+M2e) and coronavirus (POL) epitopes generated enhanced immune responses in comparison to peptide containing only POL. Th1 and Th2 immune responses to coronavirus POL and SP were observed. Serum neutralizing activity was demonstrated against IAV. Studies are underway to examine neutralizing antibodies against HCoV NL-63 and multiple variants of SARS-CoV-2. Highly conserved epitopes in these composite peptide vaccines may provide an important strategy to prevent infections with IAV or SARS-CoV-2 and mitigate the threat of co-infection.

Disclosures

All Authors: No reported disclosures.
1873. Comparative performance of RTqPCR vs RTddPCR for the detection of SARS-CoV-2 in wastewater (WW) collected from a range of sites and scales across the sewer network of Calgary, Alberta
Authors: M. Waddell Barbara Jean , Oberding Lisa , Acosta Nicole , Chavarriaga Maria Bautista , McCalder Janine , Toppings Noah , Du Kristine , Pradhan Puja , Sedaghat Navid , Beaudet Alexander , Man Lawrence , Cabaj Jason , Bhatnagar Srijak , Ruecker Norma J , Achari Gopal , Cathryn Ryan M , Meddings Jon , Conly John M , Frankowski Kevin , Hubert Casey R J , Pillai Dylan , Parkins Michael
Published: December 2022

Background

We sought to compare WW SARS-CoV-2 RNA detection across a range of sites and scales using RTqPCR and RTddPCR. Figure.

Methods

Composite-24h WW was collected from a WW treatment plant (WTP; n=18), a neighborhood (Nb1; n=12) and three hospitals; H-1, H-2, and H-3 (3-sites; A-C)(n=84). RNA was extracted using the 4S-silica column method. RTqPCR (QuantStudio5, ThermoFisher) and RTddPCR (C1000 Thermal Cycler and QX200 Droplet Reader, BioRad) quantified SARS-CoV-2 RNA nucleocapsid (N2, US CDC) and envelope (E Sarbeco, Corman et al 2020) in triplicate. Fisher’s exact test was used to compare assay sensitivity. Correlations between modalities and RNA - clinically-confirmed COVID-19 cases (defined by postal code of primary residence using 5-day rolling average) was assessed using Persons correlation.

Results

114 samples were tested (02/23/2021-04/22/2021). SARS-CoV-2-N2 was identified in 90/114 (79%) by RTqPCR and 89/114 (78%) by ddPCR (p=1). SARS-CoV-2 E was found in 72/114 (63%) by RTqPCR and 90/114 (79%) by ddPCR, p=0.01. Correlations between modalities were strongest for N2 relative to E across all sites (see Table).

N2 correlated with clinically diagnosed cases for both modalities greater at the level of the WTP (RTqPCR; r=0.8972, p< 0.0001and ddPCR; 0.933, p< 0.0001) relative to neighborhood (RTqPCR; r=0.6, p=0.04 and ddPCR; 0.60, p=0.04). E correlated to a lesser degree with cases at WTP (RTqPCR; r=0.65, p=0.0035 and ddPCR; 0.88, p=< 0.001) and neighborhoods (RTqPCR; r=0.40, p=0.20 and ddPCR; r=0.43, p=0.16).

Conclusion

SARS-CoV-2 detection of N2 was similar between RTqPCR and RTddPCR across a range of sites and scales in the sewershed, and this correlated best with clinical cases whereas E detection was superior with ddPCR.

Disclosures

All Authors: No reported disclosures.
1878. Demographic and Clinical Characteristics of COVID-19 Reinfection
Authors: Hoard Robert , Coate Eric , Macias Elizabeth A , Jackson Luke B , Barsoumian Alice E , Okulicz Jason , Markelz Elizabeth
Published: December 2022

Background

COVID-19 reinfection is generally defined as having 2 positive SARS-CoV-2 tests greater than 90 days apart. The clinical implications and impact of COVID-19 reinfection are not completely understood. We evaluated clinical and demographic characteristics of patients with COVID-19 reinfection.

Methods

All SARS-CoV-2 polymerase chain reaction (PCR) tests performed at Joint Base San Antonio (JBSA), from March 27, 2020 through January 19, 2022 were analyzed. COVID-19 reinfection was defined as having 2 positive PCR tests >90 days apart. Available data for comorbidities, travel, COVID-19 vaccination status, SARS-CoV-2 genotype, symptoms, hospitalization, and treatments were compared for first and second infections.

Results

A total of 310,704 SARS-CoV-2 PCR tests performed of which 25,543 (8.2%) were positive at JBSA during the study period. Patients with COVID-19 reinfection (n=532; 4.2%) were identified and 266 (50%) charts reviewed. The mean age was 36.5 (±15) years and approximately half were males and active duty members (Table 1). The median time from first to second infection was 326 days (IQR 160-385). Patients were predominantly unvaccinated (91.4%) at initial infection, however unvaccinated status was less common (40.2%) at second infection (40.2%; P< 0.0001). A significantly higher proportion of patients were symptomatic at first infection (88.3%) compared to second infection (51.5%; P< 0.001). Pneumonia diagnosis was significantly higher (4.9% vs. 0.4%; P=0.0011) whereas hospitalization was similar (2.6% vs. 2.3%; P=0.0788) for first compared to second infection. Among hospitalized patients, critical illness was common for first infection (57.1%) but none of the patients were critically ill with their second infection. A third episode of infection was rarely observed (1.5%). Of 80 genotype samples available, 14 (30%) were paired samples. Among all paired samples different genotypes were responsible for reinfection (Table 2).

Conclusion

Patients with COVID-19 reinfections were less likely to be symptomatic, had lower severity of illness, and typically had a different SARS-CoV-2 genotype at second infection. Reinfection occurred despite COVID-19 vaccination in many patients, which highlights the need to develop novel strategies for vaccination.

Disclosures

All Authors: No reported disclosures.
2320. Novel checkpoint modifier lowers T cell activation threshold and enhances and broadens vaccine-induced responses to chronic viral infections
Authors: Hasanpourghadi Mohadeseh , Luber Andrew , Currie Sue , Magowan Colin , Zhou Xiangyang , Ertl Hildegund C J
Published: December 2022

Background

Vaccines aim to induce immune responses that prevent disease. They may also clear chronic infections or reduce tumor progression. Vaccine adjuvants augment immune responses, in general, by providing stimulatory signals. Our focus has been on a different type of adjuvant that enhances vaccine-induced T cell responses by modulating the herpes virus entry mediator (HVEM) pathway. The B and T cell attenuator (BTLA) is expressed on naïve T cells and, upon binding to HVEM on antigen presenting cells, dampens signaling through the T cell receptor. HVEM binds with a different domain to the co-stimulator LIGHT. Within a trimolar BTLA-LIGHT/HVEM complex, inhibition prevails. Herpes simplex virus (HSV-1) glycoprotein D (gD) attaches to the BTLA binding site of HVEM and as it has higher binding affinity outcompetes BTLA binding and allows for co-stimulation through LIGHT. This results in enhanced signaling through the T cell receptor and thereby augments and broadens CD8+ T cell responses as we showed with chimpanzee adenovirus (AdC) vector vaccines for several viral antigens.

Methods

Immunogenicity in rodents was evaluated following one or two immunizations with AdC vectors expressing antigens of HIV (gag), HPV-16 (E7/6/5), HBV (core & pol), influenza virus (nucleoprotein) and SARS-CoV2 (nucleoprotein), with or without gD. Vaccine-induced CD8+ T cell responses, including their magnitude, functions, duration, and breadth were characterized. Vaccine efficacy was also evaluated.

Results

Vaccination with gD-antigen fusion proteins increased CD8+ T cell frequencies to all of the antigens tested (Fig) and improved efficacy. Addition of gD increased stimulation of CD8+ T cells to subdominant epitopes and thereby enhanced breadth of responses.

Conclusion

Checkpoint modification of the HVEM pathway with a gD-antigen fusion protein produces potent, prolonged, and broad responses of CD8+ T cells to immunodominant and subdominant epitopes. The latter is especially important for chronic viral infections, where, due to exhaustion of T cells to dominant epitopes therapeutic efficacy of vaccines may rely on expansion of T cells to subdominant epitopes. Clinical studies to evaluate therapeutic vaccination for chronic HBV are planned.

Disclosures

All Authors: No reported disclosures.
1888. Implementation of COVID-19 Surveillance Testing Procedures in Dental School
Authors: Shoemaker Holly , Bullock Jeri , Stratford Kristina , Weller Melodie L , Hobson-Rohrer Wendy L , Hobson-Rohrer Wendy L , Samore Matthew H , Mayer Jeanmarie , Visnovsky Lindsay D
Published: December 2022

Background

Dental practitioners and students of dentistry are potentially at increased risk of COVID-19 infection due to frequent usage of aerosol-generating procedures. To mitigate risk to patients and providers, the University of Utah School of Dentistry began regular surveillance PCR testing of its patient-facing faculty, staff, and students in May 2020.

Methods

Surveillance testing occurred every other week for non-vaccinated individuals and continued through February 2022. After May 2021, fully vaccinated individuals were tested monthly and encouraged to seek additional testing if symptoms or an exposure occurred. We assessed risk of positive test among faculty, student, and staff groups through a Cox proportional hazards regression, accounting for multiple events and time-dependent variables with the Andersen-Gill model. To account for inconsistent testing after vaccination, time was examined as number of tests rather than calendar time.

Results

In total, 410 participants were followed during the observation period, with an average of 22 (SD 10.0, RNG 1-50) tests per person. A total of 9,452 tests were performed. There were 158 positive tests, with 60 (38%) occurring in January 2022 alone. When analyzed by themselves, staff and student groups were significantly more likely to test positive (HR 1.98, 95% CI 1.15-3.42; HR 2.16, 95% CI 1.29-3.63 respectively) compared to faculty. However, once additional covariates were accounted for, the relationship was no longer significant (Staff: HR 2.15, 95% CI 0.92-5.05; Students: HR 2.38, 95% CI 0.88-6.40).

Risk of COVID-19 within Dental School

Hazard Ratios for testing positive for COVID-19 among different groups within the dental school. Vaccination is accounted for as time since last vaccine, with separate categories for one dose, and 2 or more doses combined. Time examined as test number.

Conclusion

More than a third of all positive tests during the 22-month study occurred during one month of the Omicron wave. This sudden increase in positive tests was not observed in previous surges, and demonstrates the intensity of the Omicron wave. Additionally, we did not find a significant difference between patient-facing groups who had different work exposures. While this may be due to effective preventative measures, within the dental setting we do not see evidence that work role and resulting exposures increase risk.

Disclosures

All Authors: No reported disclosures.
1895. SingHealth COVID-19 Disease Registry
Authors: Shoon Jin Yee , Conceicao Edwin P , Yang Yue , Arora Shalvi , Ong Eng Hock Marcus , Chan Sze Ling , Sim Xiang Ying Jean , Venkatachalam Indumathi
Published: December 2022

Background

One of Singapore’s national strategies for the COVID-19 pandemic was containment. Efforts included a fourteen-day quarantine of close contacts, were subjected to an entry and exit SARS-CoV-2 PCR test, the latter being done between 11-14 days post exposure. Additionally, symptomatic contacts were tested for SARS-CoV-2. We aim to determine the trend in COVID-19 incubation periods during three distinct pandemic waves corresponding to different SARS-CoV-2 variants.

Incubation Period

Incubation period of the prevalent SARS-CoV-2 variant in circulation

Methods

This is an ecological study and information collected from the SingHealth COVID-19 Registry, a database of all inpatients admitted to any of the SingHealth hospitals. For patients under quarantine, the start date of the quarantine period was assumed to be the last date of exposure to the index case. Incubation period was determined by the duration between date of exposure and date of the first positive SARS-CoV-2 PCR test. The prevalent strain in circulation was identified from the Singapore database in the GISAID collection. Only variants of concern, as categorized by WHO, Alpha (23rd Jan 2020 – 1st Mar 2021), Delta (5th May 2021 – 31st Oct 2021) and Omicron (1st Jan 2022 – Present) were considered. For the Omicron variant, quarantine was discontinued, hence the last date of arrival from international travel was assumed to be the date of exposure.

Results

From January 2020 to March 2022, there were 19,905 patients in the COVID-19 registry, of whom 11,235 were under quarantine and 8,612 had preceding international travel. Of the 11,235 patients under quarantine, 8,189 patients were infected when SARS-CoV-2 Alpha variant and 3,046 patients were infected when SARS-CoV-2 Delta variant were in circulation. Of the 8,612 patients with preceding travel, 6,503 patients were infected when SARS-CoV-2 Omicron variant was in circulation. The median incubation period for the Alpha variant was 11 days (IQR: 7-14 days) versus 3 days (IQR: 2-4 days) for the Delta variant versus 3 days (IQR: 0-5 days) for the Omicron variant. Pairwise comparisons between the variants were (p-value = < .001)

Conclusion

The significant differences between incubation periods of the SARS-CoV-2 variants in circulation poses a challenge to containment efforts and has emphasize the importance of dynamic national strategies.

Disclosures

All Authors: No reported disclosures.
1907. Initiation of Comfort Measures Only Care in the Medical Intensive Care Unit during the COVID-19 Pandemic
Authors: Jacobs Max , Rovnan Helene , Ramanujam Deeksha , Hamza Amina , Caucci Stephen , Cheema Tariq
Published: December 2022

Background

The COVID-19 pandemic brought an unprecedented disruption to many hospital standard operating procedures including changing family visitation policies. As an infection control policy, most hospitals denied or limited visitors and patient families were updated via phone or video conferencing. There are several plausible reasons to suspect that altered communication techniques and heightened public awareness of critical illness during the pandemic impacted end of life care and decision making.

Methods

We conducted a retrospective observational cohort study from a tertiary care hospital to determine if more patients in the ICU were transitioned to comfort measures only (CMO) care during COVID than in the same period the year before when COVID had not yet arrived in the United States (“pre-pandemic”). Collected information included demographics (Table 1), reason for ICU, co-morbidities, code status at admission, length of ICU stay, cost of care during ICU admission, and disposition at discharge. All analyses began using the Kolmogorov -Smirnov test. Normally distributed continuous variables are compared between groups using the independent-samples t-test. Non-normally distributed continuous variables are compared between groups using the Mann-Whitney U test.

Results

There were no statistically significant differences in baseline demographic and clinical characteristics of patients admitted to the medical ICU during the pre-pandemic versus pandemic periods (Table 1). Among the 266 patients admitted during the pre-pandemic period, 11.7% (31/266) were discharged with CMO code status. Among the 160 patients admitted in the pandemic period, 8.8% (14/160) were discharged with CMO code status (Table 2). The median APACHE score was significantly higher in the pre-pandemic period ([median=18 (interquartile range = 11) compared to the pandemic period ([median=15 (interquartile range = 1), (Mann-Whitney U = 17146.50, p = .008). The cost of an ICU admission during the pandemic period increased 0.099%. Table 1Baseline demographic and clinical characteristics of patients admitted to the medical ICU pre- versus post-pandemic (n = 426).Table 2Discharge status code and outcomes of patients admitted to the medical ICU in the pre- versus post-pandemic (n = 426).

Conclusion

This study shows that despite the highmorbidity and mortality associated with COVID, during the study time periods, the limitation of in-person visitors did not have an impact on the frequency of patients transitioned to CMO or decreased hospital expenditure.

Disclosures

Tariq Cheema, MD, GSK,BI,ASTRA ZENECA,Regenoron: Honoraria.
1910. A Highly Effective ID Physician and Infection Preventionist-led Interactive Webinar Series for Infection Prevention and Control Training Among Frontline Healthcare Workers
Authors: Ostdiek Riley P , Salman Ashraf M , Soma Mounica , Fadul Nada , Stream Sarah , German Dan K , Tyner Kate , Cortes-Penfield Nicolas W
Published: December 2022

Background

Nebraska Infection Control Assessment and Promotion Program (ICAP) is funded by Nebraska Department of Health and Human Services through Centers for Disease Control and Prevention (CDC) grants to support Infection Prevention and Control (IPC) activities in the state. In early 2022, ICAP launched COVID-19-specific basic infection prevention and control (IPC) training to frontline healthcare providers (HCPs) through a discussion-based webinar series using curricular materials created by the CDC Project Firstline. Here, we report pre- and post-training survey responses demonstrating improvement in participants' perceived knowledge across a number of IPC domains.

Methods

Training was completed over a 14-week period via a weekly, interactive 30-minute webinars with a new topic covered each week. A survey was administered to participants prior to the webinar series and at the conclusion of training to assess effectiveness. The pre-survey evaluated HCP confidence in their knowledge of each of the 14 topics to be covered in the course. The post-survey evaluated both confidence and perceived value in each of the training topics.

Results

Prior to the training series, a mean 40.3% of participants judge themselves “very confident” in IPC topics, versus 52.7% “somewhat confident” and 7.1% “not confident” (figure 1); by the end of the training, these levels had improved to 85.4%, 14.3%, and 0.4%, respectively (figure 2). The largest gains in the category “very confident” concerned “source control” (+65%) and “COVID-19 variants” (+63%). A majority of participants perceived each topic covered in the series to be “very valuable” (figure 3); 98% of participants indicated interest in a future IPC training series and 95% indicated that they would recommend the training series to a colleague. Figure 1Results of a pre-course survey on knowledge of training topics completed by participants.Figure 2Results of a post-course survey on knowledge of training topics completed by participants.Figure 3Results of a post-course survey on value of the training course completed by participants.

Conclusion

This survey data suggests that a discussion-based webinar using CDC Project Firstline materials is highly effective at conveying fundamental concepts in infection control to frontline HCPs. Moreover, HCPs rated themselves as likely to return, suggesting this format is a promising modality for simple and widespread dissemination of IPC training.

Disclosures

M. Salman Ashraf, MBBS, Merck & Co. Inc: Grant/Research Support.
1912. Addressing Uncertainty: An Evidence-Based, Data-Driven, Decision Matrix for Healthcare Operations During The COVID-19 Pandemic
Authors: Ausborn Valerie , Ostrosky-Zeichner Luis , Ellsworth Misti G , McInnis-Cole Tawanna A , Verrill Kristine Aleman , Lutz Shannon , Thomas Georgia , McCarthy James
Published: December 2022

Background

Uncertainty and continuously changing guidance for COVID-19 response has taken a toll on the mental health of all individuals. Growing uncertainty within a healthcare system can create stress and confusion, ultimately affecting patient care. We designed an evidence-based, data-driven, decision matrix for healthcare operations that adapts COVID-19 mitigation measures in a predictable fashion according to the CDC community risk level and wastewater positivity data.

Methods

A multidisciplinary team reviewed mitigation measures, published and internal data on the value and yield of these measures, and different operational aspects of a major healthcare system that are affected by COVID-19. The team also reviewed publicly available community risk metrics to then a create a decision matrix that adjusts mitigation measures and operational aspects in a predictable fashion according to COVID-19 risk in the community.

Results

When COVID-19 rates were low during the pandemic the yield of temperature and symptom screening was 0.19% people screening out and the yield of pre-procedure testing was 0.17% patients testing positive. Taking that into account, as well as published literature and public health guidance, we built the COVID-19 decision matrix shown in the figure, with adaptations for in-patient, out-patient, long-term care sites. The decision matrix was then posted online with a qualification that the enterprise COVID-19 status would only change with sustained changes ( > 2 weeks) in CDC Community risk level or wastewater positivity. The enterprise COVID-19 status is inserted in all enterprise communications for operational awareness. The response to the COVID-19 decision matrix has been overwhelmingly positive by staff and visitors, with no safety or operational problems in the first month of implementation.

Conclusion

An evidence-based, data-driven, decision matrix provides predictable mitigation measures and operational responses to changes in the COVID-19 community risk levels and alleviates workforce uncertainty.

Disclosures

All Authors: No reported disclosures.