bluuebunny/crossref_metadata_2025 huggingface dataset:
2270. Dealing with an old foe –Assessment of Knowledge, Attitude, and Practices: A survey on management of Staphylococcus aureus bacteraemia among Indian Physicians
Authors: Ravindra Akshatha , Kumar Deepak , Meena Durga Shankar , Naguthevar Santhanam , Bohra Gopal Krishana
Published: November 2023

Background

Staphylococcus aureus bacteraemia (SAB) is associated with high morbidity, mortality, and healthcare costs. Effective management of SAB significantly improves outcome. There is significant gap in the guidelines and clinical practice. This survey was conducted with aim to assess opinions and practice patterns in management of SAB among Indian clinicians.

Methods

We conducted a cross-sectional respondent-driven survey, using a 45-item, anonymous, voluntary, multiple-choice google form questionnaire among clinicians in India, after obtaining ethical approval from the institute. We distributed survey via social media, WhatsApp, and E-mail. Survey responses were analysed using SPSS, Version 25.0.

Results

The total of 125 practicing clinicians responded to this survey. Questions where systematically divided into treatment of choice for MSSA, MRSA, additional investigations, persistent bacteraemia, and adjunctive anti-toxin therapy. Around 57% of the respondents have 1-10 episodes of SAB every month. For suspected SAB, most respondents (74%) preferred vancomycin as empiric therapy. If MSSA was identified, 66.7% initiated on Anti staphylococcal penicillin, while in MRSA vancomycin was selected by majority (80%) (Figure 1 & 2). Most clinicians (74%) perceived 1st generation cephalosporins non-inferior to ASPs. Infectious diseases referral for SAB was undertaken in only in about 56% of the cases, with 25% respondents citing non-availability of ID specialist in the institute. Repeat blood cultures and echocardiography was performed by most respondents. Lack of consensus was apparent in diagnosis and management of persistent bacteraemia and oral switch of therapy (Figure 1 & 2).Most respondents managed SAB with at least 14 days of parenteral antibiotics in several scenarios. But, in patients with complicated SAB there was significant practice variation (Figure 3).

Figure - 1

Drug of choice in MSSA, MRSA and management of persistent bacteraemia according to the respondents

Figure 2

Persistent bacteraemia definition according to the respondents along with the additional tests performed

Conclusion

There were some areas of consensus, but this survey highlights considerable practice variation among clinicians. Although the value of ID consultation in SAB management has been established by multiple studies, this survey demonstrates that there remains ample opportunity to further define best practices and optimize management of this complex disease.

Disclosures

All Authors: No reported disclosures
2273. Azithromycin Use Before and During COVID- 19 and Impact of Implementing Evidence-based Guidelines
Authors: Shams Sherin , Nafady-Hego Hanaa , Thomas Anil G , Saleem Samah , Hanana Fathima , Malik Aimon , Kaleeckal Anvar Hassan , Latif Ali Nizar , Umar Aftab Mohammad , Alkhal Abdullatif , Almaslamani Muna , Abou-Samra Abdul-Badi , Butt Adeel A
Published: November 2023

Background

Early in the COVID-19 pandemic, results from small uncontrolled studies led to azithromycin being proposed as an effective treatment in patients with COVID-19. Numerous subsequent randomized controlled trials and observational studies have failed to demonstrate azithromycin’s effectiveness in COVID-19. The magnitude of azithromycin overuse, particularly for COVID-19 remains undocumented. We sought to quantify the use of azithromycin before and during the COVID-19 pandemic in a national healthcare system where specific evidence-based guidelines were rapidly implemented for judicious use of various suggested COVID-19 treatments.

Methods

The study was conducted at Hamad Medical Corporation in Qatar, which was the single provider of inpatient care for COVID-19 in Qatar. Evidence-based guidelines were implemented in Qatar for use of azithromycin in June 2020. For our study, all azithromycin prescriptions between 2019-2022 were retrieved from the electronic medical records. Number of azithromycin courses prescribed, and rate/100,000 population were calculated and compared over time. A course was defined as any azithromycin prescription with no gap of > 10 days. A course was deemed related to COVID-19 if written within -3 to +10 days of a positive SARS-CoV-2 PCR. A one-way repeated measured analysis of variance was conducted to evaluate the null hypothesis that there was no change in azithromycin use before and during COVID-19.

Results

During the study period, a total of 203,806 azithromycin courses were prescribed for 166,062 individuals. Overall number of courses increased in the first 2 quarters of 2020 (average 12,857/quarter in 2019 to average of 19,297 in Q1-Q2 of 2020) and then dropped precipitously to 9,881/quarter over the next 6 quarters. COVID-19 related azithromycin courses peaked in 2020-Q2 (13,691) and dropped subsequently to 2,836 for 2020-Q3, 1,410 for 2020-Q4; 5,465 for 2021-Q1, and 4,288 for 2021-Q2. Stringent evidence-based guidelines implemented in June 2020 for use of various COVID-19 therapeutics coincided with the rapid drop in azithromycin use for COVID-19.

Conclusion

While azithromycin prescriptions increased immediately after the COVID-19 pandemic, a rapid decline was observed immediately after implementing evidence-based guidelines

Disclosures

Adeel A. Butt, MBBS, MS, Gilead Sciences: Grant/Research Support|Merck and Company: Grant/Research Support
2274. Trends in Empiric Antibiotic Utilization for Patients Hospitalized with Community-Onset SARS-CoV-2 Infections and Viral Sepsis During the COVID-19 Pandemic
Authors: Shappell Claire N , Klompas Michael , Kanjilal Sanjat , Chan Christina , McKenna Caroline S , Rhee Chanu
Published: November 2023

Background

Empiric antibiotic use in patients hospitalized with COVID-19 was common early in the pandemic despite low rates of bacterial co-infection. Little is known, however, about trends in antibiotic prescribing for patients with COVID-19 with and without viral sepsis.

Methods

We retrospectively identified all adults admitted to 5 Massachusetts hospitals from March 2020 to November 2022 with community-onset COVID, defined by positive SARS-CoV-2 PCR prior to hospital day (HD) 3. Community-onset COVID sepsis was defined as a positive PCR and ≥1 acute organ dysfunction (advanced oxygen support, vasopressors, elevated lactate, or changes in baseline creatinine, bilirubin, or platelets) before HD 3. We calculated quarterly rates of initial (before HD 3) and prolonged (≥4 days/first week) empiric broad-spectrum antibiotics in COVID patients with and without sepsis and estimated quarterly odds for receipt of prolonged antibiotics relative to the first pandemic quarter using logistic regression to adjust for age, comorbidities, and positive blood or sputum cultures before HD 3.

Results

Of 431,017 total hospitalizations, 21,563 (5.0%) had community-onset COVID, of whom 3,829 (17.8%) had COVID sepsis. COVID patients with sepsis had a positive blood or sputum culture before HD 3 in 8.8% of encounters versus 1.8% of those without sepsis. Initial antibiotics were given to 69.0% of COVID patients with sepsis vs 34.3% of those without sepsis and were continued for ≥4 days in 49.5% and 18.6% respectively. Crude quarterly rates of prolonged antibiotic use decreased from 66.9% to 47.6% for COVID patients with sepsis (IRR 0.96/quarter, 95% CI 0.95-0.97) and from 31.0% to 16.4% for COVID without sepsis (IRR 0.95/quarter, 95% CI 0.94-0.96) (Figure). Trends in prolonged antibiotic use were similar after risk adjustment (quarterly aOR 0.92 for COVID with sepsis, 95% CI 0.90-0.94 and aOR 0.91 for COVID without sepsis, 95%CI 0.90-0.92).

Trends in Prolonged Antibiotics Prescribing for Hospitalized Patients with SARS-CoV-2 with and without Viral Sepsis

Conclusion

During the first 2.5 years of the pandemic, empiric antibiotics were given to 2/3 of COVID patients with community-onset sepsis and 1/3 of COVID patients without sepsis, usually for at least 4 days, despite low rates of documented bacterial co-infection. Antibiotic use in both groups, however, significantly declined over time.

Disclosures

Michael Klompas, MD, MPH, UpToDate, Inc.: Royalties for chapters on pneumonia Sanjat Kanjilal, MD, MPH, GSK: Advisor/Consultant|Pattern biosciences: Advisor/Consultant|Roche: Honoraria|Uptodate: Royalties Chanu Rhee, MD, MPH, Cytovale: Advisor/Consultant|Pfizer: Advisor/Consultant|UpToDate, Inc.: Honoraria
2282. Characterizing Antibacterial Regimen Modification, Patient Characteristics, and Outcomes for Patients with Complicated Gram-Negative Bacterial Infections
Authors: Yamaki Jason , Yucel Emre , Watanabe Alexandre H
Published: November 2023

Background

There are few studies describing the rationale or frequency of empiric or directed therapy treatment modification behaviors among patients with complicated Gram-negative bacterial infections (GNBI). We sought to characterize patient and treatment characteristics, details of regimen modification, and patient outcomes.

Methods

This retrospective chart review included patients, admitted from 1/1/2019-12/31/2020 to Hoag Memorial Hospital, with a complicated GNBI due to an extended spectrum cephalosporin resistant pathogen. Patient charts were reviewed for demographics, antibiotic (ABX) modifications, rationale and timing of modifications, and patient outcomes. ABX modifications were defined as GNB ABX switched, added, or removed.

Results

The study cohort included 400 patients (median age 74.5 years; 61% male). The predominant sources were lung (34%) and bloodstream (26%) for single cultures and bloodstream (33%) and urine (26%) for multiple cultures. The most common pathogens were ESBL organisms (36% overall with E. coli accounting for 81% of cases), and Pseudomonas spp. (40%). Inpatient initial empiric therapies included piperacillin-tazobactam (32%), cefepime (24%), meropenem (15%), and ceftriaxone (17%). ABX regimens were modified up to 6 times in 72% of patients. Median [IQR] time to first modification was 41 [21, 70] hours. For initial modifications, 70% were escalations, and most empiric modifications were based on preliminary culture results (56%) and lack of patient response or decompensation (25%). No difference in mortality and readmission was observed based on presence of ABX modifications.

Conclusion

Many patients experienced modification to GNB empiric and targeted antibacterial regimens. In almost all cases, rationale for change was documented. No difference in patient outcomes was observed. Despite changes to ABX regimens, patient outcomes are not improved possibly due to shortcoming of existing antibiotic portfolio. Furthermore, the numerous changes in therapy observed may reflect the lack in identifying patients with resistant GNB organisms early in admission. This highlights the needs of more effective and novel antibiotics and importance of identifying patients at risk for resistant GNBI.

Disclosures

Jason Yamaki, PharmD, PhD, Merck & Co., Inc.: Grant/Research Support Emre Yucel, PhD, MERCK: I am a full time Merck Employee and own stocks in the retirement plan provided by Merck.|MERCK: Stocks/Bonds Alexandre H. Watanabe, PharmD, Merck & Co., Inc.: Employee
2299. Genomic Epidemiology of SARS-CoV-2 in Metropolitan Detroit
Authors: Kaur Jagjeet , Gurdziel Katherine , Wasinski Benjamin , Vakeesan Nivisa , Raza Sayed Hassan , Liu Wanqing , Zervos Marcus , Suleyman Geehan
Published: November 2023

Background

The COVID-19 pandemic, resulting from the rapidly evolving SARS-CoV-2 virus, has drastically impacted health systems and economies worldwide. Genomic sequencing is critical for the surveillance of SARS-CoV-2 to monitor the rapidly evolving virus and identify new strains.

Methods

583 isolates from Henry Ford Health were retrospectively profiled across 3 years (117 isolates in 2020; 39 in 2021; 427 in 2022). DNA was extracted using Kingfisher viral isolation kit; RT-PCR screening was used to identify isolates with cycle threshold < 32 for whole genome sequencing (WGS). Libraries were generated using QIAseq DIRECT SARS-CoV-2 Kit, followed by Illumina sequencing (MiSeq or NovaSeq 6000; 300 cycles). Lineage analysis of the SARS-CoV-2 consensus genome sequences generated from samtools variant analysis pipeline was determined using Nextclade and Pangolin software.

Results

Sequences were classified into 11 unique clades across 108 lineages by Nextclade and Pangolin, respectively. Almost three-fourths of the sequenced isolates were from 2022. 117 (20%) genomes were from the early pandemic (2020) and were clustered into 8 clades: 19A, 19B, 20A, 20B, 20C, 21 J (Delta) and 21L (Omicron). Most of the 2022 genomes (72%) were in clade 20C from lineage B.1, identified during the outbreak in Europe. 15 (13%) genomes had clade 19A (lineage B) and 1 had 19B (lineage A.3), identified early in the pandemic in Wuhan, China. Of the 39 (7%) genomes from 2021, the majority (82%) clustered into clade Delta 21J that originated in India. Only 2 (5%) of the genomes from 2021 had Alpha variant of concern (21I) from the lineage B1.1.7, which were suspected to be more transmissible. Of the 427 (73%) genomes from 2022, 393 (92%) had variants within Omicron variant of concern (21L), with 79 different lineages; 1 was Omicron variant 21K from the lineage BA1.1. Other clades observed in the 2022 batch were 19A (6%), 20A (0.2%), 20B (0.2%), 20C (0.2%) and 21M (1%).

Conclusion

Our genomic surveillance data suggest that SARS-CoV-2 infections at the local level mirrored global outbreaks. This underscores the importance of robust genomic surveillance efforts to inform public health planning and practice.

Disclosures

Marcus Zervos, MD, Contrafect: Advisor/Consultant|GSK: Grant/Research Support|Johnson and Johnson: Grant/Research Support|Pfizer: Grant/Research Support
2300. Incidence of COVID-19 in Irish Healthcare Workers: Preliminary Results from PRECISE-5
Authors: Kenny Claire , McGrath Jonathan , Kelly Gavin , Walsh Shane , Moran Conor , Flynn Lee , Byrne David , Flynn-Dowling Irene , Allen Niamh , Rooney Peadar , Martin Greg , Doherty Lorraine , Fleming Catherine , Bergin Colm
Published: November 2023

Background

Healthcare workers (HCW) are the ideal population to track the evolving epidemiology of SARS-CoV-2. Surges in breakthrough SARS-CoV-2 infection and quarantine regulations leads to staff absence at a time when hospital resources are already burdened.

Methods

All HCWs in 2 large teaching hospitals were invited to participate in this prospective longitudinal cohort study in November 2022. Information on demographics, SARS-CoV-2 infection history and COVID-19 vaccination dates/brands was collected. Baseline serology for anti-Nucleocapsid (N) and anti-Spike (S) antibodies was performed. Cohort seroprevalence was compared to a prior study phase (November 2021). Monthly follow-up e-surveys collected information relating to incident SARS-CoV-2 infections, symptom duration and work days missed.

Results

1261 participants enrolled (Table 1). 25/1261 (0.08%) were unvaccinated. 1103/1261 (87.5%) had received a primary vaccine series and at least one booster.

1260/1261 (99.9%) of participants were anti-S seropositive. 1008/1261 (79.9%) participants were anti-N seropositive. In comparison, serology performed in November 2021 showed anti-N antibody seropositivity in 23.4% (p< 0.0001). 377/1261 (29.9%) participants denied having a prior SARS-CoV-2 infection; of these, 178/377 (47.21%) were anti-N seropositive suggestive of previously undiagnosed infection.

Response rate to monthly surveys over the first 14 weeks of the study (Weeks 45-52 of 2022 and Weeks 01-06 of 2023) was 54.3%. 121/1261 (9.6%) of participants reported a positive SARS-CoV-2 test (PCR or Antigen). Incident infections peaked at Weeks 50-52 of 2022 (Fig. 1), reflective of the national trend. 41/121 (33.8%) reported a symptomatic infection, with median symptom duration 7.5 days. Over 14 weeks, total number of work days missed secondary to SARS-CoV-2 infection was 589 days (median 5 days missed per HCW).

Conclusion

In this interim analysis, 9.6% of participants reported an incident SARS-CoV-2 infection over 14 weeks. This was in the context of high baseline seropositivity for anti-N antibody and vaccination uptake. This suggests that SARS-CoV-2 continues to circulate widely. While morbidity and mortality is low, there are significant consequences including rostered working days lost in healthcare settings.

Disclosures

All Authors: No reported disclosures
2306. A serosurvey of healthcare workers caring for, or handling specimens from, individuals exposed to, or diagnosed with, SARS-CoV-2 infection (COVID-HEROES)
Authors: Pradhan Alyssa , Dwyer Dominic E , Hueston Linda , Asquith Will , Dotel Ravindra , Nanan Ralph , Wood Nicholas , Howard-Jones Annaleise , O’Kane Gabrielle M , Stuart Rhonda , Whyler Naomi , Chua Kyra , Gilbey Timothy , Bemand Timothy , Weatherall Chris , Hammoud Mohamed , Martinello Marianne , Rai Neela Joshi , O’Sullivan Matthew
Published: November 2023

Background

COVID-HEROES is a multicentre study of Australian healthcare workers (HCW) assessing 1) incidence of and risk factors for SARS-CoV-2 infection and 2) serological response to SARS-CoV-2 vaccination and infection.Figure 1:Cases of SARS-CoV-2 over time by diagnostic method

Methods

We conducted a multi-centre, prospective observational cohort study of Australian HCWs from January 2020 – January 2023, evaluating incidence of, and risk factors for, SARS-CoV-2 infection. HCWs underwent monthly surveys to assess SARS-CoV-2 occupational exposure, vaccination status and infection and serology testing to detect antibody response to vaccination (measured by IgG immunofluorescent antibody titre) or infection (development of SARS-CoV-2 nucleoprotein (NP) IgG antibodies measured by ELISA). Factors associated with infection were identified using logistic regression models.

Results

575 participants completed 4882 surveys and 4325 serological tests over 36 months. Median enrolment duration was 8.4 (IQR 2.2-17.4) months. 160/575 (28%) of participants reported SARS-CoV-2 infection diagnosed by polymerase chain reaction (PCR) and/or rapid antigen test (RAT). 101/160 (64%) participants with known infection developed NP antibodies. A further 41 participants, without reported infection developed NP antibodies, indicating unrecognised infection (Figure 1).

153/160 (96%) known infections occurred after December 2021, corresponding to the Omicron wave, despite 25-50% of participants reporting occupational exposure to SARS-CoV-2 patients throughout the study period. 571/575 participants developed IgG response following two doses of SARS-CoV-2 vaccine, 6 of whom seroreverted. A logistic regression model of risk factors for HCWs contracting SARS-CoV-2 infection (Table 2) did not identify significant association between occupational exposure and infection (OR 1.49, CI 0.87- 2.57, p = 0.15).

Conclusion

In this 3-year prospective cohort, we report detailed occupational SARS-CoV-2 exposures to assess nosocomial acquisition risk, including symptomatic and unrecognised infection. We demonstrate low rates of infection until community prevalence increased, despite significant workplace exposure, indicating effective use of protective precautions in the Australian healthcare setting.

Disclosures

All Authors: No reported disclosures
2311. Predictive cut-off values for anti-N and anti-S antibodies for COVID-19 risk identification
Authors: Rebellón Sánchez David E , Llanos-Torres Julio , Tafurt Eric , Rosso Fernando
Published: November 2023

Background

The role of anti-N and anti-S antibody tests as a monitoring strategy for identifying patients at risk of developing COVID-19 is not clearly elucidated. Our study explored in a cohort of hospital workers whether the positivity of these antibodies linked to infection and/or vaccination was associated with a decrease in the risk of infections and sought to estimate a predictive cut-off point for the development of COVID-19 in the first 6 months of measurement.

Methods

A prospective observational study was conducted among hospital workers at a university hospital in Cali, Colombia. Measurements of COVID-19 antibodies were taken before the onset of the third, fourth, and fifth waves of COVID-19 cases. Anti-N and Anti-S total antibodies were measured using Elecsys® Anti-SARS-CoV-2 Immunoassay (Roche).

Results

We include 480 participants, 71.8% females and median age of 32 years (IQR: 27-39); 60.62% were healthcare workers involved in the care of COVID-19 patients. It was found that having a history of COVID-19 (aRR 0.49 (95% CI 0.34-0.70)), being vaccinated in the last 6 months (aRR 0.13 (95% CI 0.07-0.24)), having positive anti-N antibodies in the last 3 months (aRR 0.62 (95% CI 0.44-0.87)), and having positive anti-S antibodies in the last 3 months (aRR 0.55 (95% CI 0.31-0.97)) were associated with a lower risk of developing COVID-19. A cutoff point ≤ 150 COI for anti-N levels and ≤1,900 BAU/mL for anti-S levels was found to have a better predictive performance. The chosen cutoff point for anti-N achieved a sensitivity of 98.2%, with a specificity of 12.4%, a negative predictive value (NPV) of 98.5%, and a positive predictive value (PPV) of 10.2%, with an AUC of 0.55 for predicting COVID-19 in the next 6 months. Having anti-S antibodies ≤ 1900 BAU/mL was found to have a sensitivity of 58.1%, specificity of 55.5%, NPV of 85.3%, PPV of 22.9%, and an AUC of 0.63.

Conclusion

Our study suggests that having a positive anti-N or anti-S antibodies result may be associated with a lower risk of developing COVID-19. We also identified predictive cut-off points for anti-N and anti-S antibody levels that may be useful in identifying individuals at a higher risk of developing COVID-19 in the next 6 months. However, further studies are needed to confirm these findings and determine their generalizability to other populations.

Disclosures

All Authors: No reported disclosures
2329. What Causes a Cluster to Grow? Factors Associated with a Nosocomial COVID-19 Cluster at a University Hospital in Central Tokyo
Authors: Osaka Hilary , Tagashira Yasuaki , Gu Yoshiaki , Takahashi Kunihiko
Published: November 2023

Background

Coronavirus disease 2019 (COVID-19) remains a significant threat to hospital infection control. Despite the decrease in severity and mortality associated with changes in the variants of concern and increased vaccination, SARS-CoV-2 transmissibility remains high, and nosocomial clusters continue to be reported in various countries. Although COVID-19 may be detected in multiple patients and healthcare workers (HCWs) in a given ward within a few days, it is uncertain whether these cases will develop into a large cluster.

Methods

The present, retrospective cohort study of nosocomial COVID-19 clusters was conducted at Tokyo Medical and Dental University Hospital from January 2022 to January 2023 using data from the hospital’s infection prevention and control team. A nosocomial COVID-19 cluster was defined as consisting of more than 2 COVID-19 cases occurring within 5 days in the same ward. Cases with a clear epidemiological link and clusters outside the ward were excluded. We collected information regarding community trends, the index case details, and each cluster's ward profile. Predictors of cluster expansion to more than 5 cases were also examined.

Results

66 clusters were identified at the hospital during the study period. The median number of COVID-19 cases per cluster was 3 (range: 2-22), and their median duration was 5 days (range: 1-27). 37 (56.1%), 25 (37.9%), and 4 (6.1%) clusters comprised both inpatients and HCWs, only HCWs, and only patients, respectively. The index case of 51 clusters (77.3%) was a HCW. 18 (27.3%) and 47 (72.7%) clusters contained > 5 and < 5 cases, respectively. No significant intergroup difference was found in terms of community prevalence, index case and ward characteristics, the rate of close contact or history of previous clusters. However, “clusters occurring during the non-epidemic period” and “infections > 3 occurring within 3 days” tended to develop into clusters containing more than 5 cases.

Conclusion

Nosocomial clusters can occur anywhere, and predicting them is challenging. Further research is needed to identify the factors leading to cluster development and to establish effective infection prevention and control measures.

Disclosures

All Authors: No reported disclosures
2333. Knowledge, attitudes, and practices regarding vaccination against COVID-19 among medical students at a private university in Lima – Peru
Authors: Ramos-Rojas Benjamin , Lopez-Rivera Sebastian , Tafur-Bances Karla , Gonzales-Zamora Jose A , Alave Jorge
Published: November 2023

Background

Vaccination against COVID-19 is one of the most important measures to reduce the spread, morbidity, and mortality of the disease.

Methods

We conducted a cross-sectional study to evaluate knowledge, attitudes, and practices regarding vaccination against COVID-19 in medical students at Universidad Peruana Cayetano Heredia (UPCH), for which an online survey was administered through e-mail and WhatsApp in July 2022. The following independent variables were evaluated: To be in the clinical phase of medical school (last four years), having more online classes ( >= 4 semesters with non-face-to-face classes), having received >= 3 doses of COVID-19 vaccine, and having reliable sources of information (scientific articles, conferences, and seminars). Through linear regression multivariate analysis, we assessed the factors associated with the number of correct answers (knowledge), the standardized attitude index (attitudes), and the number of vaccine doses received (practice).

Results

A total of 352 medical students completed the survey. 96.6% of participants knew that vaccines improved immunity, and 91.2% believed they were effective in reducing hospitalizations, severe illness, and death. 98% of students agreed that the benefits of vaccination outweighed the risks, 90.9% would recommend the population to get vaccinated, and 59.1% agreed that vaccines were safe. 99.7% of respondents have received at least one dose of vaccine, of which 100% received at least two doses, 88% three, and 4.8% four or more. In the multivariate analysis, we found that being in the clinical phase of medical school was associated with a higher knowledge and a higher standardized attitude index. Having received >=3 doses was associated with a higher standardized attitude index. Lastly, having a higher standardized attitude index was associated with having received more vaccine doses. (Table. 1)

Table 1

Conclusion

Regarding vaccination against COVID-19, medical students at UPCH have a high level of knowledge, a positive attitude, and good practices. Our study suggests that educational strategies in the pre-clinical phase may be needed to improve knowledge and attitudes regarding vaccination. Also, a higher standardized attitude index may predict a higher number of vaccine doses.

Disclosures

All Authors: No reported disclosures
2335. Up-to-date COVID-19 vaccination coverage among healthcare personnel in nursing homes —National Healthcare Safety Network
Authors: Ananth Sushmitha , Reses Hannah E , Dubendris Heather , Barbre Kira A , Wong Emily , Lu Meng , Bell Jeneita
Published: November 2023

Background

To prevent morbidity and mortality associated with COVID-19 among nursing home residents, both residents and healthcare personnel (HCP) should remain up-to-date (UTD) with recommended COVID-19 vaccines, including the updated bivalent boosters. As of the first quarter of 2023 (December 26th, 2022 - March 26th, 2023) , the current Centers for Disease Control and Prevention (CDC) recommendation for UTD is defined as completion of primary series and receipt of bivalent booster, or primary series completion only if not yet eligible for booster. The objective of this project was to assess national COVID-19 UTD percentage among HCP in nursing homes by facility-characteristics.

Methods

We analyzed vaccination data reported by nursing homes to the CDC’s National Healthcare Safety Network during January 23rd–February 5th, 2023. Based on the right-skewed distribution of the percentage of HCP who are UTD, median was selected as the main summary measure of central tendency. We calculated median UTD (%) nationally and by facility-size tertiles (measured by number of HCP that were eligible to have worked at a facility for at least 1 day during the week of data collection), social vulnerability index (SVI) tertiles, and urbanicity.

Results

Among 14,857 nursing homes, median UTD (%) among HCP was 13.9% ; among smaller (< 92 total HCP) and larger facilities ( >145 total HCP) was 14.9% and 13.3%, respectively. Median UTD (%) for facilities located in low and high SVI areas was 15.3% and 12.8%, respectively. Median UTD (%) was 11.6% for facilities in non-metropolitan areas and 15.1% among those in metropolitan areas.

Conclusion

COVID-19 median UTD (%) among HCP working in nursing homes in the U.S. was low overall and in all stratifications by facility size, SVI, and urbanicity. This suggests that additional strategies are needed to improve UTD coverage in this population.

Disclosures

All Authors: No reported disclosures
2343. SARS-CoV-2 Spike Conformation Essentially Influences Vaccine Immunogenicity – Results from Two Clinical Phase I Trials of the Vector Vaccine Candidates MVA-SARS-2-S and MVA-SARS-2-ST
Authors: Fathi Anahita , Dahlke Christine , Hardtke Svenja , Mellinghoff Sibylle C , Mayer Leonie , Weskamm Leonie M , Krähling Verena , Müller-Kräuter Helena , Ly My L , Friedrich Monika , Hesterkamp Thomas J , Volz Asisa , Sutter Gerd , Becker Stephan , Addo Marylyn
Published: November 2023

Background

Recombinant Modified Vaccinia virus Ankara (MVA) is a replication-deficient viral vector platform with a favorable safety profile that is currently developed for multiple indications, including vaccines against emerging infections. We assessed the safety and immunogenicity of two MVA-based vaccine candidates against COVID-19 encoding the native or pre-fusion stabilized SARS-CoV-2 spike antigen, namely MVA-SARS-2-S and MVA-SARS-2-ST, in two clinical Phase I trials.

Methods

We conducted a first-in-human trial of the vaccine candidate MVA-SARS-2-S (NCT04569383) and a Phase Ib trial of the successor vaccine MVA-SARS-2-ST (NCT05226390) in healthy, SARS-CoV-2 immune-naïve adults aged between 18-55 (MVA-SARS-2-S) and 18-64 (MVA-SARS-2-ST) years. MVA-SARS-2-S expresses the native, full-length spike glycoprotein of SARS-CoV-2 (S), while MVA-SARS-2-ST delivers a pre-fusion stabilized spike antigen (ST). Both trials were designed as open-label dose-escalation trials and vaccinations were administered as a prime-boost regimen on days 0 and 28. Detailed safety and immunogenicity assessments were conducted at multiple timepoints throughout the study until day 168.

Results

In NCT04569383, 30 individuals received either 1 x 107 ± 0.5 log IU (IU=International Units, n=15, lower dose) or 1 x 108 ± 0.5 log IU (n=15, higher dose) of MVA-SARS-2-S. In NCT05226390, 8 participants received a lower (≥ 1 x 107 IU) and 7 participants a higher (≥ 5 x 107 IU) dose of MVA-SARS-2-ST. Both vaccines were well-tolerated and no vaccine-related severe adverse events (SAEs) occurred in either trial. However, seroconversion rates, measured as binding anti-SARS-CoV-2 S1 antibodies, could only be observed in 3/15 participants in the high dose cohort and none in the low dose cohort after vaccination with MVA-SARS-2-S. In contrast, all participants who received MVA-SARS-2-ST (n=15) achieved seroconversion independent of administered dose.

Conclusion

Both vaccine candidates were safe and well-tolerated. While MVA-SARS-2-S did not induce adequate immunogenicity, vaccination with the pre-fusion stabilized successor vaccine MVA-SARS-2-ST induced seroconversion in all vaccinees, demonstrating the significance of SARS-CoV-2 spike antigen conformation for vaccine immunogenicity.

Disclosures

Anahita Fathi, MD, Biotest: Honoraria Sibylle C. Mellinghoff, MD, Gilead: Grant|Octapharma: Advisor/Consultant
2353. SARS-CoV-2 Variants among US Veterans after COVID-19 Bivalent Vaccine Administration
Authors: Holodniy Mark , Pei Ying , Stack Gary , Wade Christopher L , Agrawal Yashpal , Barasch Nicholas , Baddoura Fady , Carmen Frias-Kletecka M , Stacey Klutts J , Wang-rodriguez Jessica
Published: November 2023

Background

The US Department of Veterans Affairs (VA) created the Sequencing For Research, Clinical, Epidemiology (SEQFORCE) Program in July 2021 to conduct SARS-CoV-2 Whole Genome Sequencing (WGS). Herein, we describe SARS-CoV-2 variants associated with COVID-19 infection, including after bivalent vaccination.

Methods

Demographics, COVID-19 vaccinations, hospitalizations, SARS-CoV-2 variants, and Charlson comorbidity index variables were extracted from VA data sources from 7/1/21-4/1/23. Eligible respiratory samples required a positive RT-PCR result from any platform with cycle threshold < 30. WGS was performed using 3 different platforms (Clear Labs, Illumina, ThermoFisher) at the 9 laboratories and one analytic pipeline (PraediGene, Bitscopic) using Pangolin and Nextclade. Post-vaccine COVID-19 infection was defined as > 2 weeks after COVID-19 vaccine receipt.

Results

Over 41,000 samples from 150 VA clinical sites across all geographical locations in the country have been analyzed by 9 SEQFORCE laboratories since July 1, 2021 (Figure 1), including 28,800 after vaccine breakthrough infection (Table 1). Since October 1, 2022, 3,087 patients had SARS-CoV-2 variants characterized including 986 after bivalent vaccination, 1,191 who were fully vaccinated (including Janssen), but not boosted and didn’t receive a bivalent vaccine dose, and 910 who were never vaccinated (Figure 2) according to VA records. Those who received bivalent vaccine were significantly older, male, and had higher Charlson morbidity scores compared to those not receiving a bivalent vaccine. There was no difference in infection rates based on type of bivalent vaccine received. Bivalent vaccine recipients had significantly more XBB and less BA.5 variants, compared to not receiving a bivalent vaccine (p < 0.0001 for both comparisons).

Conclusion

VA established a SARS-CoV-2 sequencing consortium to track variants for clinical and epidemiological indications. Sample submission was voluntary and therefore may have limited geographic, temporal and clinical diversity among patient samples analyzed. Significantly more XBB and less BA.5 variants were found after bivalent vaccination infection compared to other contemporaneous variants among those not receiving bivalent vaccine.

Disclosures

M. Carmen Frias-Kletecka, MD, Sanofi: Honoraria
2959. Urinary tract colonizing abilities of fosfomycin (FOF) non-susceptible Klebsiella pneumoniae (KP) inner colonies (IC) arising from disk diffusion (DD) in an ascending mouse urinary tract infection (UTI) model
Authors: Bixby Morgan , Collins Lindsey , Salay Jenna , Clabots Connie , Hirsch Elizabeth B
Published: November 2023

Background

DD is a common method for FOF susceptibility testing against Enterobacterales, despite a lack of breakpoints for non-E. coli organisms. When extrapolating these breakpoints, methods for reading zone diameters from the breakpoint setting organizations are often extrapolated as well. With CLSI and EUCAST in disagreement on interpretation of IC that arise from DD, it is imperative that the clinical relevance of these IC is determined. We sought to determine the urinary tract colonizing ability of one clinical KP isolate via an ascending mouse UTI model.

Methods

The parent isolate, KP131—a clinical isolate from Boston, MA—had an MIC of 8 µg/mL and its IC from DD had an MIC of 1024 µg/mL. Immune competent female CBA/j mice (n = 35) were inoculated with an equal mix of KP 131 parent/IC culture via urinary catheter at 1µL/g mouse weight, which delivered a total of 1011 CFU/mL per mouse bladder. At 48 hours post-inoculation, mice were sacrificed, and kidneys/bladders were aseptically collected and individually homogenized. Homogenate was plated on both standard Mueller-Hinton agar (MHA) and MHA plates containing 32 µg/mL FOF + 25µg/mL glucose-6-phosphate. The number of parent colonies were determined by subtracting the FOF-supplemented plate counts from the standard MHA counts and proportions compared via Kruskal-Wallis test.

Results

Of 35 mice infected, 14.3% (n = 5) died prior to harvest. Bladder colonization occurred in 80% (n/N = 24/30) of mice and in one or both kidneys in 67% (n/N = 16/24) of mice when bladders were colonized; 25 total kidneys were colonized. Among these, IC accounted for 44.8% of bacterial burden in the bladder and 54.6% in the kidneys. There was no significant difference in the colonizing abilities of IC compared to the parents in the bladder (p = 0.289). However, the IC colonized at a significantly higher rate (p = 0.046) than the parent isolate in the kidney tissue.

Conclusion

Results from this preliminary study show that KP IC have the ability to colonize the urinary tract at near equal rates to the parent culture when in competition in a mouse UTI model, including a significantly greater colonization in kidney tissue. While this work is limited by use of a single parent/IC pair, future directions include expanding to additional KP isolates with various FOF phenotypes.

Disclosures

Elizabeth B. Hirsch, PharmD, Melinta Therapuetics: Honoraria|Merck and Company, Inc.: Grant/Research Support
2388. Factors Associated with COVID-19 Vaccination Among Racial/Ethnic Minority Populations with HIV, Miami-Dade County, Florida, 2022
Authors: Trepka Mary Jo , Ramirez-Ortiz Daisy , Jean-Gilles Michele , Ladner Robert , Li Tan , Sheehan Diana
Published: November 2023

Background

People with HIV (PWH) are at increased risk for COVID-19 complications and thus can significantly benefit from COVID-19 vaccination. PWH are also more likely to belong to racial/ethnic minority groups that have been underrepresented among vaccinated individuals. The objective of this analysis was to identify Health Belief Model (e.g., perceived susceptibility to and severity of COVID-19, perceived barriers, and benefits of COVID-19 vaccination) and Social Ecological Model (i.e., intrapersonal, interpersonal, and community/institutional-level) factors associated with vaccine uptake among PWH.

Methods

The cross-sectional survey was administered by telephone in English, Spanish or Haitian Creole from January–March 2022 to a sample of 299 adult PWH receiving medical case management services through the Miami-Dade County Ryan White Program (MDCRWP). Participants who received a primary vaccine series were classified as fully vaccinated, and those that received only 1 dose of a 2-dose vaccine series or no doses were classified as not fully vaccinated. Multivariable logistic regression was used to estimate adjusted odds ratios (aORs) of full vaccination with 95% confidence intervals (CIs). The final adjusted model included all sociodemographic characteristics selected a priori, as well as covariates with a p-value < 0.2 in bivariate analyses. Analyses were weighted to be representative of the race/ethnicity and sex distribution of clients in the MDCRWP.

Results

The weighted percentages for full vaccination was 83.8% for the entire group, and 88.9% among Hispanics, 72.0% among African Americans, and 67.5% among Haitians. Being fully vaccinated was associated with Hispanic compared with African American race/ethnicity (aOR 5.44; 95% CI 1.50-19.77), not endorsing any misconceptions about COVID-19 vaccines (aOR 8.26; 95% CI 1.38-49.64), reporting encouragement to get vaccinated from their sources of information (aOR 20.82; 95% CI 5.84-74.14), and perception that ≥ 50% of social network was vaccinated (aOR 3.35; 95% CI 1.04-10.71) (Table 1).

Conclusion

Results highlight the importance of promoting accurate information from sources deemed trustworthy, and social networks in COVID-19 vaccine uptake among PWH.

Disclosures

All Authors: No reported disclosures
129. Evaluation of Two-Step Clostridioides difficile Testing on Treatment Exposure
Authors: Bennett Nicholas , Wilson Sydney , Aragon Laura , Boyd Sarah E
Published: November 2023

Background

Clostridioides difficile can colonize or cause symptomatic disease from mild diarrhea to severe colonic inflammation requiring surgical intervention. Multiple C. difficile diagnostics are available and national guidelines recommend standalone or combination testing methods. Testing has mostly shifted to polymerase chain reaction (PCR)-based, which has shown up to a 50% increase in reporting of C. difficile infection (CDI). A two-step testing method has also been used to discern colonization versus active infection. The National Healthcare Safety Network has proposed changes to CDI reporting to include results and treatment, emphasizing the importance of diagnostic and antimicrobial stewardship.

Methods

In 2021 Saint Luke’s Health System moved from C. difficile PCR standalone to two-step testing with PCR and enzyme immunoassay (EIA) toxin test. If PCR is positive, an EIA is run. Both results are reported including interpretation guidance. A retrospective cohort study was conducted to evaluate if two-step testing impacts antibiotic prescribing rates for C. difficile. The pre-implementation group included PCR-only and post- implementation was split into PCR +/ EIA - and PCR +/ EIA + groups.

Results

Treatment rates for C. difficile did not significantly change after implementation of two-step testing (100% pre- vs 92% PCR +/ EIA - and 97% PCR +/ EIA +, p = 0.093). For PCR +/ EIA - results, treatment initiation more often occurred prior to results being available compared to the post-implementation PCR +/ EIA + group and pre-implementation group (30.3% PCR +/ EIA - vs 19.6% PCR +/ EIA + and 7.8% pre-implementation, (p = 0.028)). C. difficile antibiotic prescribing rates at discharge were no different between groups as the highest rates of treatment continuation were seen in the PCR +/ EIA - group (79.4% PCR +/ EIA - 72.5% pre-implementation vs 71.7% PCR+/ EIA +, p = 0.706).

Conclusion

Despite PCR +/ EIA - results, clinicians tended to treat patients irrespective of PCR-only or two-step results. The impact of two-step C. difficile testing on treatment rates was limited and prescribing rates did not significantly change. The findings of this study warrant investigation into alternative solutions to promote aligned diagnostic and antimicrobial stewardship.

Disclosures

All Authors: No reported disclosures
2403. Outcomes in Infective Endocarditis due to Granulicatella species and Abiotrophia defectiva
Authors: McCartney Cindy , Bartley Patricia , Shrestha Nabin K
Published: November 2023

Background

Infective Endocarditis (IE) due to Granulicatella sp. and Abiotrophia defectiva (formerly known as nutritionally variant streptococci - NVS) remains a clinically important entity given difficulty in diagnosis, optimal management, and possible treatment failure outcomes. These microorganisms account for roughly 4-8% of all IE cases. To the best of our knowledge this study entails the largest single center registry in the US of Granulicatella sp. and A. defectiva IE looking at patient characteristics, survival and relapse outcomes and susceptibility data.

Methods

Retrospective chart review of 35 patients (13 A. defectiva, 20 Granulicatella sp. and 2 labelled as NVS) with IE admitted to our facility from January 1st, 2008, to January 1st, 2023.

Results

Patient characteristics including valves affected, presenting symptoms and complications can be seen in Table 1. Seven patients (20% - 5 for A. defectiva and 2 for Granulicatella sp.) had failed medical management at outside facilities prior to admission at our center. Valve replacement or repair was performed on 31 (88.6%) patients. Molecular testing was performed on 28 (80%) isolates of which all had positive identification. Susceptibilities were obtained in 22 (63%) isolates as summarized in Table 2 below. All isolates were found to be vancomycin-susceptible, and varying degrees of susceptibilities to ceftriaxone and penicillin depending on the species. Vancomycin therapy was used in 11 (31.4%) patients, ceftriaxone in 19 (54.3%) patients (combination of vancomycin and ceftriaxone in 3 patients), and penicillin in 8 (22.9%) patients. Adjuvant aminoglycoside therapy was used in only 2 (5.7%) patients (one combination with ampicillin and one with vancomycin). Average length of IV antibiotic therapy was 6 weeks post-surgery, and 5 patients were treated with an oral tail after IV antibiotics. Survival curves since hospitalization are demonstrated in Figure 1. There were no treatment failures or relapses of IE due to these organisms.

Conclusion

The majority of patients presented with constitutional symptoms, heart failure and embolic events. Five-year survival exceeded 80% and there were no relapses in this series. Most importantly, outcomes were excellent without the use of aminoglycosides contrary to guideline recommendations.

Disclosures

All Authors: No reported disclosures
2407. Multidisciplinary Endocarditis Team (MET): Establishing a Baseline of Infective Endocarditis in People Who Use Injection Drugs (PWID)
Authors: Patel Kaya , Duffield Olivia , Spivack Stephanie , Schultz Sara K
Published: November 2023

Background

Infective endocarditis (IE) is a serious infectious complication of intravenous drug use. Treatments include prolonged courses of IV antibiotics, surgical valve repair/ replacement, vacuum-assisted thrombectomy, and pulmonary autograft (Ross Procedure). We created a multidisciplinary team of treating physicians to review all cases of IE at our large academic medical center in Philadelphia starting in March 2023. To establish a baseline prior to the creation of MET, we describe the microbiological and clinical findings, treatment, and outcomes of a cohort of PWID found to have IE.

Methods

We queried our EMR for admissions with patients that had documented opioid use disorder with injection behavior and positive blood cultures from September of 2021 to March of 2022. We conducted a retrospective chart review of these patients and collected data regarding their hospital course and treatment.

Results

We identified 39 patients with definite IE (modified Duke’s criteria). The predominant organisms were MRSA (19, 43%), MSSA (14, 32%), and group A streptococcus (9, 20%). Thirty-six (92%) patients underwent TTE and 8 (20%) underwent TEE to evaluate for vegetations. On echocardiography, 23 (59%) vegetations were noted: 11 tricuspid valve, 3 mitral valve, 2 aortic valve, and 2 pulmonic valve. Five vegetations were found on prosthetic valves: 2 tricuspid valve, 2 pulmonic valve, and 1 aortic valve. Of the 23 patients with vegetations, 11 (48%) met ACC/AHA criteria for procedural intervention. Of these patients, 7 (63%) received intervention (1 valve repair, 2 valve replacements, 2 Ross Procedures, 2 vacuum-assisted thrombectomies). Intervention occurred on average of 7.8 days from diagnosis. Sixteen (41%) patients completed a full course of antibiotic therapy. Of the 23 (59%) patients that did not complete antibiotics, 5 were prescribed oral 2nd line therapies. Fifteen (38%) patients were readmitted within 90 days and 5 (13%) experienced mortality within 30 days. (Figure 1)

Conclusion

Treating IE in PWID is challenging and often requires a multidisciplinary approach. We demonstrated high rates of right and left sided IE as well as high rates of surgical intervention pre-implementation of MET. We anticipate an improvement in clinical outcomes with the implementation of MET.

Disclosures

Sara K. Schultz, MD FACP FIDSA, AbbVie: Advisor/Consultant