bluuebunny/crossref_metadata_2025 huggingface dataset:
271. Determining Risk Factors Associated with an Increased Incidence of Pulmonary Embolism: A Multi-Center Study of 3,675 Patients
Authors: Wang Lucas , Abualfoul Mujahed , Aten Kristopher , Azimi Ariella , Canela Victor , Hoang Lawrence , Prathivada Sri , Vu Michael , Zhao Sherry , Sidhu Manavjot
Published: December 2022

Background

Coronavirus Disease 2019 (COVID-19) is associated with an increased incidence of pulmonary embolism (PE). Both conditions increase hospital complications and mortality, especially when exhibited concurrently. Unfortunately, both conditions may present similarly, and physicians often have a difficult time finding clinical indicators to suggest pursuing further evaluation of a PE during a COVID-19 infection.

Methods

Using a multi-center facility database, we conducted a retrospective analysis of 3,675 COVID-19 patients at Methodist Health System from March 2020 to December 2020. COVID-19 infection was determined via molecular PCR testing and PE was determined by computed tomography (CT) scan with angiography. Patient demographics and laboratory values were determined by a manual review of patient charts. Chi-Square test was used to analyze observed variables. Odds ratios were calculated for variables with a statistically significant difference (p < 0.05).

Results

Of the 3,675 patients diagnosed with COVID-19, 150 (4.1%) were diagnosed with PE. Elevated D-dimer level had a statistically significant association with increased rate of PE (OR 0.1988, 95% CI 0.0727 – 0.5438, p < 0.001). Factors such as elevated C-reactive protein (p = 0.61), IL-6 (p = 0.26), smoking history (p = 0.70), age over 65 (p=0.54), BMI over 25 (p = 0.42), and history of chronic kidney disease (p = 0.16) did not show a significant association with PE incidence. Of note, patients with PE during admission were seen to have an increased incidence of intubation (OR 0.40, 95% CI 0.2660 – 0.6029, p < 0.001).

Conclusion

Our study suggests that COVID-19 patients with elevated D-dimer have higher odds of having a PE. This study also suggests that COVID-19 patients that develop a PE during hospitalization are more likely to require intubation.

Disclosures

All Authors: No reported disclosures.
275. Evaluating the COVID-19 Pandemic in US Veterans: Transitioning from Delta to Omicron Variants
Authors: Lier Audun J , Lobo Zeena , Psevdos George
Published: December 2022

Background

During the COVID-19 pandemic many new variants of the SARS-CoV-2 virus have evolved. The omicron variant is the latest of concern and has numerous mutations in the spike protein (SP) which may alter COVID19 vaccine and therapeutic efficacy. We assessed whether COVID19 vaccination status would be protective among US Veterans (USV) who were diagnosed with SARS-CoV2 infection and performed an epidemiological analysis of this cohort.

Methods

A retrospective chart review was performed of USV with PCR confirmed SARS-CoV-2 infection who presented to Northport Veterans Affairs Medical Center between 11/1/2021 and 4/15/2022. Demographic information, vaccine status, medical comorbidities, SARS-CoV2 infection history, medical therapy receipt, need for hospitalization, SARS-COV-2 sequencing, and SP receptor-biding domain (RBD) IgG levels were reviewed. Two sample t-test and Chi-square analyses were performed.

Results

605 USV were diagnosed with SARS-CoV2, median age was 62 years, 559 (92.4%) were male, 474 (78.3%) Caucasian and 77 (12.7%) Hispanic. 426 (70.4%) received at least one COVID19 vaccine dose, largely mRNA (n=400, 66.1%). Median time from vaccine dose to SARS-CoV2 diagnosis was 211 days (1-468). 26 (4.3%) USV had a previous history of SARS-CoV2 infection and 38 vaccinated USV had RBD-SP IgG titers (positive > 1 S/CO) at time of presentation, median 6.8 S/CO (0.06 to 71.21). Unvaccinated USV had a higher mean body mass index (31.0 vs. 30.0, p=0.04), and more commonly carried a diagnosis of COPD or asthma (20.0 vs. 11.8%, p=0.0005). A greater number of vaccinated USV utilized tobacco (44.2 vs 6.1%, p< 0.0001) or opioids (6.8 vs 1.1%, p< 0.0001). Unvaccinated USV more often required remdesivir (RDV) or dexamethasone (DEX) therapy (10.6 vs 6.6%, p=0.04). There was no difference in hospitalizations, monoclonal antibody use, or all-cause mortality between groups. Omicron BA.1 was first found on December 13, BA.2 on March 9 and final Delta variant on January 12.

Demographic characteristics of the entire cohort, as well as by vaccination status

Monthly SARS-CoV2 infections among US Veterans

Monthly infections with delta and omicron SARS-CoV2 variants among vaccinated and unvaccinated US Veterans between 11/1/21 and 4/15/22

Daily SARS-CoV2 infections among US Veterans

Daily infections with delta and omicron SARS-CoV2 variants among vaccinated and unvaccinated US Veterans between 11/1/21 and 4/15/22

Conclusion

Omicron and Delta SARS-CoV-2 infections occurred in both vaccinated and unvaccinated USV, including among vaccinated persons with detectable neutralizing IgG titers. Unvaccinated USV were more likely to utilize RDV and DEX, suggesting severe infection was more common in this group.

Disclosures

All Authors: No reported disclosures.
282. Occurrence of adverse events and factors related to prognosis in a cohort of patients hospitalized with COVID-19 at University hospital - UNICAMP, Brazil.
Authors: Luz Maitê V , Silva Julian F , Ceccato Hugo D , Souza Paulo J , Villar Pedro M E , Mendes Paulo R A , Resende Mariângela R , Pereira Mônica C , Conterno Lucieni O
Published: December 2022

Background

In Brazil, 30.378.061 cases of COVID were reported and 662.866 deaths up to April 27 of 2022. Hospital infections and other hospital adverse events may increase the risk of death in patients with COVID-19.

Methods

Cohort study that included 650 adult patients hospitalized with a diagnosis of SARS CoV-2 infection at Hospital HC-UNICAMP from March/20 to March/21.

Results

Of the 650 patients included in the study, 139 (21.38%) died. Comparing the patients who died vs those who survived, we observed a statistically significant difference in the occurrence of thromboembolic and vascular events (23% vs 9.8%; OR 1.332; 95%CI 1.12-1.59; p < 0,0001), ICU admission (84.9% vs 39.6%; OR 0.675; 95%CI 0.62-0.74; p< 0.0001) and the occurrence of HI: bloodstream infections (30.2% vs 8.6%; OR 1.62; 95%CI 1.31-1.99; p< 0.0001), VAP (52.5% vs 12.3%; OR 1.882; 95%CI 1.57-2.26; p< 0.0001) and UTI (27.3% vs 7.2%; OR 1.672; 95%CI 1.32-2.11; p< 0.0001). Gram negative bacteria were the most isolated (62.1%), especially K. pneumoniae, A. baumannii and P. aeruginosa, followed by gram positive bacteria (27%) and fungi (13.8%).

When evaluating patients who had thromboembolic events, we observed a statistically significant association with male gender (15.9% vs 7.9%; p 0.003), mean initial D-Dimer values (10,418.00 ng/mL vs 3011.34 ng/ml; p 0.003); acute renal failure (19.1% vs 9.3%; p 0.001) and the occurrence of HI (24.4% vs 7.3%; p< 0.0001).

The following factors associated with ICU admission were identified: diabetes mellitus (59.3% vs 40.5%; p< 0.0001); obesity (58.3% vs 41.7%; p 0.003); O2 saturation at admission < 88% (67.8% vs 32.2%); acute renal failure (78.6% vs 21.4%; p< 0.0001) and the occurrence of HI (87.8% vs 12.2%; p< 0.0001).

Logistic regression analysis identified the following variables independently associated with death: age (OR 1,034; CI 1,015-1,052), ICU admission (OR 1,107; CI 1,596-5,868), use of vasoactive drugs (OR 2,93; CI 1,79-4,82), development of acute renal failure (OR 7,756; CI 4,537-13,26), and the occurrence of VAP (OR 2,205; CI 1,227-3,961) (Table 1). Table 1:Variables associated to death in Logistic Regression

Conclusion

Adverse events, particularly HI, have an important impact on the evolution of patients with COVID-19, reinforcing the need for prevention and control measures to be optimized as an essential part of the care for these patients.

Disclosures

Maitê V. Luz, n/a, FAPESP: Grant/Research Support Julian F. Silva, MD, FAPESP: Grant/Research Support Hugo D. Ceccato, MD, FAPESP: Grant/Research Support Mariângela R. Resende, PhD, FAPESP: Grant/Research Support Mônica C. Pereira, PhD, FAPESP: Grant/Research Support Lucieni O. Conterno, PhD, FAPESP: Grant/Research Support.
285. Post-COVID-19 Functional Status (PCFS) scale in Mexican adults: a cross-sectional study
Authors: Hernandez Lucia Martinez , Vargas-Vazquez Tania , Guerrero-Torres Lorena Lorena
Published: December 2022

Background

Over 5.74 million COVID-19 cases have been reported in Mexico as of May 1, 2022. Determining the impact of COVID-19 on functional status is essential to assess health services needs. The Post-COVID-19 Functional Status Scale (PCFS) is a patient-reported tool that evaluates functional status over time after COVID-19, listing a wide range of functional limitations. We aimed to assess the functional status of Mexican patients after recovery from COVID-19. Figure 1.Persistent Symptoms acording the PCFS scale.

Methods

This cross-sectional study was conducted from April 11 to May 1, 2022, through an online survey that included demographic and clinical data, PCFS grades 0-4 and persistent symptoms. We included Mexicans aged ≥18 years who recovered from COVID-19 (≥14 days since diagnosis), who resided in Mexico and agreed to participate. We posted the survey on Facebook and Twitter. We performed a descriptive analysis of demographic and clinical variables and assessed the relationship between symptoms and PCFS grade. Statistical analyses were conducted in Stata/SE 17.0.

Results

Of 959 respondents, 838 (87%) met inclusion and exclusion criteria. Mean age was 40 (IQR 34-46) years, 82% were female, and 40% lived in Mexico City. COVID-19 diagnosis ranged from March 21, 2020, to April 7, 2022, and mean days since diagnosis was 276 (IQR 91-480) days. Most (796, 95%) were treated as outpatients. In PCFS, 338 (40%) had no functional limitations (grade 0), 266 (32%) had negligible functional limitations (grade 1), 154 (18%) had slight functional limitations (grade 2), 44 (5%) had moderate functional limitations (grade 3), 12 (2%) had severe functional limitations (grade 4) and 24 (3%) had missing PCFS data. Overall, 654 (78%) completed the persistent symptoms section. Among them, 57% presented fatigue, 46% impaired concentration, and 10% were asymptomatic (Figure 1). Of those with >12 weeks since diagnosis, 88% (499/564) had at least one symptom.

Conclusion

Although most participants had mild COVID-19 at diagnosis, we found a high prevalence of persistent symptoms (90%) and functional limitations (60%) after recovery, revealing the devastating impact of COVID-19 on quality of life. The PCFS may be a valuable and simple tool to screen patients who could benefit from referral to rehabilitation programs, particularly in resource-limited settings.

Disclosures

All Authors: No reported disclosures.
292. Risk factor and clinical characteristics of pneumothorax and pneumomediastinum in COVID-19: a matched case-control study
Authors: Lee Se Ju , Kim Jinnam , Lee Ki Hyun , Lee Jung Ah , Kim Chang Hyup , Lee Su Hwan , Yeom Joon-sup , Ku Nam Su , Jeong Su Jin , Ahn Jin Young , Kim Jung Ho , Choi Jun Yong
Published: December 2022

Background

During the novel coronavirus SARS-CoV-2 pandemic, a considerable number of pneumothorax and pneumomediastinum associated with COVID-19 have been reported, and the incidence was higher in critically ill patients. Despite using a protective ventilation strategy, barotrauma still occurs in COVID-19 patients with invasive mechanical ventilation. This study aims to identify the risk factors and clinical characteristics of pneumothorax and pneumomediastinum in COVID-19 by a matched case-control study.

Methods

This retrospective study enrolled adult patients diagnosed with a COVID-19, admitted to a critical care unit in South Korea from 2020 March 1st to 2022 January 31st. COVID-19 patients with pneumothorax and pneumomediastinum were compared, in a 1 to 2 ratio, to a control group of COVID-19 patients without pneumothorax and pneumomediastinum, matched on age, gender, and worst National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS). Conditional logistic regression analysis was performed to assess the risk factors for pneumothorax and pneumomediastinum in COVID-19.

Results

A total of 427 patients with COVID-19 were admitted during the study period. Of these patients, 24 patients were diagnosed as pneumothorax or pneumomediastinum. When comparing the characteristics of both groups, body mass index (BMI) was significantly lower in the case group (22.8 kg/m2 and 24.7 kg/m2; P = 0.048). BMI was statistically significant risk factor for barotrauma in univariate conditional logistic regression analysis (Odds ratio (OR), 0.85; Confidence interval (CI), 0.72-0.996; P = 0.044) but not in multivariate analysis. For the patients with invasive mechanical ventilation, the period from symptom onset to intubation was longer in the case-patients (13 and 9.5 days; P = 0.032). Univariate conditional logistic regression analysis showed the statistical significance of the period from symptom onset to intubation (OR, 1.14; CI, 1.006-1.293; P = 0.041).

Conclusion

In this case-control study with age, gender, severity matching, lower BMI was associated with the pneumothorax in COVID-19, and delayed application of invasive mechanical ventilation might contribute to this complication.

Disclosures

All Authors: No reported disclosures.
298. Successful Treatment of Persistent Severe Acute Respiratory Syndrome Coronavirus 2 Infection in an Immunocompromised Patient
Authors: Overbeck Victoria , Turcinovic Jacquelyn , Qiu Xueting , Seitz Scott , Connor John , Schaeffer Beau , Hanage William P , Curry Scott R , Kuppalli Krutika
Published: December 2022

Background

The COVID-19 pandemic has been marked by long-term persistence of SARS-CoV-2 in immunocompromised patients receiving B-cell-depleting therapies, with many individuals experiencing fatal COVID-19.

Methods

We report an individual treated with rituximab who survived persistent COVID-19 over 9 months. SARS-CoV-2 positive RNA samples were sequenced using targeted amplicon NGS sequencing with backup sequencing on a nanopore platform. The resulting sequences were analyzed for genomic variance over time at the consensus and sub-consensus level.

Results

An individual with rheumatoid arthritis (RA) treated with azathioprine and rituximab (last dose in May 2020) was diagnosed with COVID-19 in July 2020 and admitted with pneumonia. After initial incomplete recovery, the patient had persistent infection through March 2021 and received both remdesivir and convalescent plasma (January 2021). The patient received three doses of mRNA vaccine (Pfizer BioNTech) in December 2020, April 2021, and November 2021, but was seronegative for nucleocapsid IgG in both January 2021 and March 2021; positive spike IgG developed by September 2021 (512 AU/ml) and December 2021 (621 AU/ml) (Figure 1). The patient recovered with new oxygen dependence (2-3L) and manages RA off B-cell depletion; they required an extended corticosteroid taper to manage organizing pneumonia and treatment for several opportunistic infections.

Viral sequencing over the course of illness indicated a persistent infection with a lineage B.1.585.3 virus that accumulated 14 mutations throughout the infection. Two mutations (S494P, S D737Y) are associated with therapy resistance and are similar to those found in other immunocompromised individuals with persistent COVID-19. Additional mutations were of unknown consequence. Figure 1:Timeline of Immunocompromised Patient’s Clinical Course of COVID-19

Conclusion

SARS-CoV-2 was able to establish persistent infection and accumulated mutations associated with therapeutic resistance; repeated vaccination was associated with successful resolution following repeated vaccination after stopping rituximab. Cessation of B-cell-depleting therapy was likely the critical factor in the patient’s recovery, but repeated vaccination was associated with a delayed seroconversion in this patient with reversibly immunosuppression.

Disclosures

William P. Hanage, PhD, Biobot Analytics Inc: Advisor/Consultant|Merck Vaccines: Advisor/Consultant.
326. Optimizing DNA Extraction from Pediatric Stool for Diagnosing Tuberculosis and Use in Next Generation Sequencing
Authors: Ness Tara , Meiwes Lennard A , Kay Alexander , Mejia Rojelio , Lange Christoph , Mandalakas Anna , DiNardo Andrew
Published: December 2022

Background

Next generation sequencing (NGS) is quickly coming to the forefront of diagnostic tools to provide efficient, highly informative information from patient samples. Recently, it was established that patients with pulmonary Tuberculosis (TB) have Mycobacterium tuberculosis DNA present in their stool samples, which can augment current diagnostic gaps. Optimizing extraction of DNA from stool for analysis via sequencing technologies is a paramount initial step to ensure accuracy of downstream sequencing applications.

Methods

Attenuated strains of Mycobacterium bovis derived from BCG were used as a model for Mtb. Human stool samples were spiked with varying known concentrations of BCG and extracted with four different DNA extraction kits (Fast DNA Spik Kit for Soil, DNeasy Blood and Tissue Kit, MagAttract HMW DNA Kit, and PowerFecal Pro DNA Kit). Each sample was subjected to quantitative polymerase chain reaction using designed primers and probes specific for identifying Mtb infection from stool. The samples underwent further analysis to assess overall DNA yield (Qubit fluorometer), DNA fragment length (Agilent tape measure), and DNA purity (Nanodrop spectrophotometer).

Results

Overall, the Fast DNA Spin Kit for Soil extraction kit showed the most optimal results. DNA isolated via this method showed the lowest cycle thresholds of Mtb amplification, indicating the most preserved amount of BCG specific DNA. In addition, this method showed the highest overall DNA yield and highest proportion of long DNA fragment lengths. Fluorometric analysis showed significant contamination in the 230 nm wavelength range, which was amended with an additional AMPure bead cleanup step.

Quantiative PCR of Spiked BCG

Quantitative PCR Cycle Threshold Values by Different DNA Extraction Kits

Conclusion

The MPFast Soil Extraction kit, when compared to three other DNA extraction kits, performed the best on stool samples for isolating BCG DNA. Overall DNA yield, DNA length, and amount of specific BCG DNA were best optimized with this method and provided the best samples for sequencing analysis. This critical step is the first of many to realize the promise of stool-based NGS.

DNA Quantity

Quantity of Total DNA by Different DNA Extraction Kits

Spectrophotometric Analysis

Analysis of Absorption of Extracted DNA by Different DNA Extraction Kits

Spectrophotometric Results

Spectrophotometry Results of DNA Samples Extracted by Different DNA Extraction Kits

Disclosures

Lennard A. Meiwes, n/a, German Center for Infection Research (DZIF): Grant/Research Support.
328. Universal PCR Testing- Is It Worth It?
Authors: Birk Navina K , Saikia Kasturi , Ramesh Mayur , Samuel Linoj , Tibbetts Robert
Published: December 2022

Background

Universal PCR and Next Generation Sequencing (uPCR/NGS) is a major advancement in microbiology. It is a highly sensitive and specific test that amplifies ribosomal RNA in samples to detect bacterial and fungal pathogens. We investigated the uPCR/NGS tests sent from Henry Ford Health (HFH) and the effect obtaining this test had on patient care.

Methods

We completed a retrospective, observational study assessing all consecutive uPCR/NGS tests obtained from at HFH from 2016-2021. This included uPCR/NGS for detection of bacterial, fungal, mycobacterium tuberculosis (MTB), and non-tuberculosis mycobacterium (NTM). All samples were of non-blood fluids and tissue samples. Patients concurrent tissue cultures and blood cultures from day of uPCR/NGS, and within 6 months of obtaining the uPCR/NGS sample were evaluated. Primary outcomes included if uPCR/NGS testing resulted in a change of choice or duration of antibiotic therapy.

Results

At HFH, 226 uPCR/NGS tests from 111 samples were analyzed. This included 83 bacterial, 51 MTB, 51 NTM, and 41 fungal uPCR/NGS tests. Of the 226 uPCR/NGS tests, 31 tests (13.7%) resulted with positive result on uPCR/NGS. A total of 31 tests (13.7%) were ordered on a known culture positive sample, and 195 (86.3%) were ordered on a culture negative sample.

Of samples sent from a culture positive sample, 7 (22.6%) resulted with positive uPCR/NGS results. 3 (42.9%) matched the tissue cultures, and 2 (28.6%) matched the patients’ blood cultures. None of the patients had any change in choice or duration of antibiotics based on uPCR/NGS results.

Of the samples sent from a culture negative sample, 24 (12.3%) samples resulted with positive uPCR/NGS results. 2 (8.3%) matched a patient’s tissue cultures and none matched blood cultures. Change in antibiotic choice or duration occurred in 16 (17.6%) patients. The samples with the highest rates of change in management included cerebrospinal fluid (42.9%), brain tissue (36.4%), cardiac valvular tissue (27.3%), lymph nodes (25%), synovial fluid (20%). Figure 1:Flowchart of Results and Impact on Management

Conclusion

Our results show that uPCR/NGS has an overall low percent of impact in clinical outcomes, but it is a useful test in when used on a culture negative sample in certain sample types, along with a high index of suspicion for infection.

Disclosures

All Authors: No reported disclosures.
336. Developing a Protein Signature of Early Latent Tuberculosis Infection.
Authors: Bark Charles , Nsereko Mary N , Kiwanuka Noah , Whalen Christopher C , Stein Catherine M , Boom Henry , Mayanja-Kizza Harriet , Nalukwago Sophie , Kakaire Robert , Jingo JohnPaul Kasule , Paramithiotis Eustache
Published: December 2022

Background

To curb the tuberculosis (TB) epidemic, new cases must be prevented. Preventive therapy is an effective intervention but treating all individuals with latent TB infection (LTBI) based on current diagnostics, tuberculin skin test (TST) and interferon gamma release assay (IGRA), is not feasible. Using proteomic analysis we are developing a peripheral blood marker of LTBI infection that would identify people at high risk for TB progression.

Methods

Plasma was collected in an ongoing TB household contact study in Kampala, Uganda in which TST-/IGRA- are enrolled and followed for IGRA/TST conversion. Longitudinal sample sets (0,6,12 months) from 81 participants including 24 TST/IGRA converters, 29 resisters (remained TST/IGRA negative), and 28 baseline positives (LTBI) underwent proteomic and multiplex cytokine analysis. Proteomic analysis was performed by multiple reaction monitoring mass spectrometry (MRM-MS) using an MRM-MS assay containing 163 host proteins represented by 392 unique peptides, all of which we have described to significantly change during Mtb infection in our previous study of household contact converters.

Results

Differential expression of proteins measured by MRM-MS and cytokine assays were assessed. The largest number of significant changes were measured in the LTBI vs Converter comparison. The vast majority of the changes were elevated expression in the converter group compared to the latent group, suggesting that all the biologies affected were induced in the converters (Figure 1). We identified protein panels that were able to predict conversion as in our earlier study. However, the protein panels defined in our earlier study that could distinguish a future converter from a future resister with high fidelity did not have a similar performance in this study. Figure 1Differential expression analysis of latent TB, LTBI vs. converter. Significant changes by both p-value (set at 0.05) and q-value (a correction for multiple comparisons, set at 0.10).

Conclusion

Peripheral blood protein changes are associated with conversion to LTBI. In this study we found that the protein panels predictive of conversion were different from our previous study. While there are many possible reasons, an important difference between the two studies was the definition of conversion: TST in the older study and QuantiFERON in the current study. We are continuing to investigate this difference and developing time-sensitive protein panels to capture recent conversion.

Disclosures

Eustache Paramithiotis, PhD, CellCarta Biosciences: Employee.
349. Characteristics and Outcomes of COVID-19 Patients with Candidemia at a Community Teaching Hospital in Chicago - One Year Follow Up.
Authors: Adeyemi Oluwadamilola A , Okoh David , Gonzaga Gregg , Cariño Sean , Kalish Steve B
Published: December 2022

Background

We previously reported an alarming increase in cases of nosocomial Candidemia at our hospital which were associated with acute COVID-19 infection (Abstract 287 IDWeek 2021). We reinstated mitigation strategies including staff education, line insertion check list and antimicrobial stewardship. 1041 patients with acute COVID-19 were admitted to our hospital in 2021 (January to December) and 6 out 12 cases (50%) of Nosocomial Candidemia were seen in patients with acute COVID-19 infection. We re-evaluated the risk factors and mortality of hospitalized COVID-19 patients with Candidemia.

Methods

We performed a retrospective chart review of the 6 patients with Candidemia and confirmed COVID-19 infection at our 292-bed community teaching hospital in Chicago, Illinois from January through December 2021. We report a descriptive analysis of the demographic characteristics, comorbidities, complications, and outcomes of these patients comparing both years.

Results

The average age of our study population was 71 years (older); 67% were male. The average hospital length of stay (LOS) was shorter 28 days. The mean time from admission to the development of Candidemia was slightly longer 18 days. Associated co-morbidities included cardiovascular diseases (CVD) in 83%, diabetes mellitus (DM), in 50%, and obesity in 50%. Treatments for COVID-19 included Steroids (100%), Remdesivir (50%) and Baricitinib (33%). All patients were managed in the intensive care unit (ICU) and 67% had a central in place at the time of Candidemia. Half of the patients (50%) required hemodialysis (HD); all patients were treated with multiple antibiotics. The average LOS in the ICU was 18 days (shorter). Despite antifungal treatment, 80% expired.

Conclusion

Incidence of Candidemia in acute COVID-19 infections decreased by 56% in one year after reinstating mitigation strategies in our hospital. However, Candidemia remains a menace in hospitalized patients with acute COVID-19 infection. Associated risk factors remain history of CVD, DM, obesity, prolonged hospital LOS, requirement for multiple CL, HD, treatment with multiple antibiotics, treatment with steroids (100%) and a long stay in the ICU. The mortality of COVID-19 patients with Candidemia remains very high.

Disclosures

All Authors: No reported disclosures.
374. Evaluation of the ChromaCode HDPCR™ RV6 RUO Assay
Authors: Trejo Marisol , Trieu Kevin P , Santellan Cynthia A , Chandrasekara Sukantha , Fathe Kristin
Published: December 2022

Background

In December of 2019, an outbreak of pneumonia was reported to the World Health Organization. The etiology of this outbreak was identified as novel coronavirus (SARS-CoV-2), which has resulted in a global pandemic. The persistence of circulating SARS-CoV-2 leads to the need for a test that can detect and differentiate SARS-CoV-2 from common causes of respiratory illnesses such as influenza and respiratory syncytial virus (RSV). ChromaCode’s HDPCR™ RV6 RUO Assay is a real time PCR test that provides qualitative detection of SARS-CoV-2, Influenza A, Influenza B, and RSV A/B from upper respiratory specimens. An evaluation in an infectious disease molecular laboratory was performed and presented herein.

Methods

A combination of residual and contrived samples were used to evaluate the ChromaCode HDPCR™ RV6 RUO assay. Residual upper respiratory samples tested with the standard of care were enrolled in this study to evaluate RV6 RUO. A total of 201 samples originally tested using Diasorin Simplexa® tests were enrolled: 17 assisted mid-turbinate, 15 contrived Flu B samples, and 179 nasopharyngeal swabs. The contrived samples were made utilizing dilutions of Zeptometrix Influenza B material (PN 0810253CF LN 325137) in negative NPS matrix to achieve final concentrations of 0.02-0.04 TCID50/mL.

Results

The ChromaCode RV6 RUO Assay had comparable results to the standard of care test. The assays had a 99.0% concordance for the Influenza A target, 100% concordance for the Influenza B target, 97.5% concordance for the RSV A/B target, and 99.5% concordance for the SARS-CoV-2 target.

Conclusion

There are several tools available for distinguishing between common respiratory illnesses, which now include SARS-CoV-2. This study demonstrated the viability of the HDPCR RV6 RUO Assay to be a solution for distinguishing between common respiratory illnesses. RV6 RUO showed a high degree of concordance with the standard of care test and highlighted the flexibility of the RV6 RUO assay to be used with multiple upper respiratory sample types. The HDPCR RV6 RUO Assay and the accompanying ChromaCode Cloud software is a user-friendly solution with minimal setup time and rapid data analysis.

Disclosures

Kristin Fathe, PhD, ChromaCode, Inc: Work there with stock options.
377. Use of Mid-Turbinate Swab (MTS) versus Throat Swab (TS) for Detection of Respiratory Pathogens in Children, Kansas City, Missouri, November 2015 – May 2019
Authors: Banerjee Dithi , Lee Brian R , Harrison Christopher J , Lively Joana Y , Whitaker Brett , Zhou Yingtao , Selvarangan Rangaraj
Published: December 2022

Background

An optimal specimen collection method is important for pathogen detection in respiratory surveillance studies. Mid-turbinate swab (MTS) in combination with throat swab (TS) were used for collecting samples from children enrolled in Kansas City site of the New Vaccine Surveillance Network (NVSN), a prospective surveillance network for acute respiratory infections. A standalone MTS is used for standard of care (SOC) testing. We compared detections from NVSN MTS+TS vs. SOC MTS samples collected ±1 day of each other to evaluate the sensitivity of the single MTS collection in children.

Methods

Nucleic acid extracts from NVSN MTS+TS samples were tested by Luminex NxTag Respiratory Pathogen Panel (NxTag RPP). SOC MTS samples were tested by BioFire® Respiratory Panel 1.7. (FilmArray). All children, aged < 18 years enrolled in the inpatient and Emergency Department for NVSN (November 2015 to May 2019) with available historical MTS SOC testing results ±1 day of enrollment were included in the study. Concordance between results of NVSN MTS+TS and SOC MTS testing was measured.

Results

Paired NVSN and SOC samples were available from 315 subjects with median age of 16.8 months (IQR 5.0 months – 61.7 months); 59.3% (189/315) were from male subjects. An overall positivity of 93.6% was noted with 295 detections by one sample or the other. Of the 295 detections, 231 (78%) detections were in both samples; 35 (12%) detections by MTS+TS; and 29 (10%) detections by MTS only. High concordance ( >90%) and very good Kappa values (Table 1) between the 2 specimen collection methods was noted for most pathogens. 72% of discrepant samples were from children with median age 13.2 months (IQR 8.0 months – 38.6 months).

Conclusion

We observed high concordance between MTS and MTS+TS for all targets. Most discrepant samples were from young children in whom adequate sampling can be challenging, perhaps reducing sensitivity. Differences in time of collection and testing, and platform differences (NxTag RPP vs. FilmArray) may have impacted our data, e.g. due to variable assay sensitivities for specific targets. Regardless of these differences, our data show comparable performance between MTS alone and MTS+TS suggesting that MTS alone may be sufficient for respiratory pathogen surveillance in children.

Disclosures

Brian R. Lee, PhD, MPH, CDC: Grant/Research Support|Merck: Grant/Research Support Christopher J Harrison, MD, Astellas: Grant/Research Support|GSK: Grant/Research Support|Merck: Grant/Research Support|Pediatric news: Honoraria|Pfizer: Grant/Research Support Rangaraj Selvarangan, BVSc, PhD, D(ABMM), FIDSA, F(AAM), BioFire: Grant/Research Support|Luminex: Grant/Research Support.
382. Are errors of omission falsely inflating hospital-onset Clostridioides difficile infection numbers?
Authors: Parada Jorge Paiva , Yussif Mohamed , Lie Louise
Published: December 2022

Background

Identification of C. difficile infection (CDI) as community onset (CO) versus hospital onset (HO) is based upon the timing of the laboratory testing. Any lab diagnosis made after day 3 of hospitalization is classified as HO-CDI, even if there is clinical evidence that the patient had CDI before lab testing was sent on day 4 or later. Capturing CDI infection early in hospitalization is essential to proper diagnosis and management of CDI.

Methods

This is a single center retrospective study of all HO-CDI cases identified from January 2018 through January 2022. All cases were reviewed to determine if patients had loose stools during days 1-3 which were not tested, as these may have been missed opportunities to diagnose CO-CDI. We used nursing flowsheet determine if the patient had soft, loose, watery, liquid or pasty stool bowel movements (BM).

Results

We identified 302 unique patients diagnosed with HO-CDI during the 4 year study period. 181 (60%) were men. The mean age 57 (range 3-98 years), with increasing case numbers with increasing age groups: age 0-18 (19/6.3%), 19-39 (39/12.9%), 40-59 (73/24.2%), ≥ 60 (171/56.6%). Mean time of HO-CDI diagnosis was 12.4 days (range 4-122 days) with a skew towards early onset HO-CDI diagnosis as 86/302 (28.5%) testing positive on days 4-6. Overall, 119/302 (39.0%) of patients had identified missed opportunities for testing stools during days 1-3 of hospitalization. 38/86 (44.2%) of patients with HO-CDI diagnosed on days 4-6 had missed opportunities for testing. 40/302 (13.2%) patients expired during the index hospitalization.

Conclusion

Better tracking of patients' symptoms, number and consistency of BMs could improve recognition of patients presenting with CO-CDI. In turn, this would help to institute earlier isolation and treatment of these patients, as well as decreasing HO-CDI resulting from late recognition of CO-CDI which may falsely inflate HO-CDI case numbers, and/or lead to secondary hospital transmission from delayed isolation of patients with CDI. Our findings likely represent a significant under estimation of the magnitude of the errors of omission of missing opportunities for early diagnosis of CDI since it based on review of nursing flowsheets which often miss the number and consistency of patients' BMs.

Disclosures

Jorge Paiva Parada, MD MPH, Shionogi: Honoraria.
389. Epidemiology of Multiple Recurrent Clostridioides difficile in the Atlanta Metropolitan Area between 2016 and 2019
Authors: Fridkin Scott , Mehta Nirja , Kraft Colleen , Goodenough Dana , Thomas Stepy
Published: December 2022

Background

Patients with multiple recurrences of Clostridioides difficile infection (CDI) have longer hospital stays and lower quality of life. Recent changes in therapies and strains of CDI make understanding recurrent CDI in the general population critical as these patients may benefit from microbiota restoring therapies rather than antibiotics alone.

Methods

Georgia’s Emerging Infections Program (supported by CDC) conducts CDI surveillance in 8 counties around metropolitan Atlanta, GA (population ∼4 million). CDI is defined as any C. difficile-positive specimen with no positive test in the prior 2 weeks. We evaluated CDI between Jan 2015 through Dec 2019 and captured recurrent CDI (CDI test date 2-52 weeks following previous CDI) for 2016-2019 which were categorized as single episode only, recurrent (2 episodes ≤ 1 year) or multiple recurrent (>2 episodes ≤ 1 year). Year was attributed to date of final episode. Census data was used to determine crude and age-specific incidence. Bivariate and multivariable logistic regression was used to estimate odds for multiple recurrent compared to single recurrent CDI with demographic, comorbidity and treatment related covariates.

Results

Over 4 years 13,745 patients had at least one episode of CDI, 2,930 (20%) had ≥ 1 recurrence and 916 (30%) of these progressed to multiple recurrence. Between 2016 to 2019, incidence of single CDI decreased 25% from 93/100,000 to 69/100,000 (P< 0.01). Multiple recurrent CDI decreased 45% from 9/100,000 to 5/100,000) (P< 0.01); incidence in the 80+ age group was highest and where decreased incidence was most dramatic during the study period (Figures). Time between 1st and 2nd episode was longer among patients with single recurrent than multiple recurrent CDI (median 12 weeks vs. 9 weeks, P< 0.01).. Independent predictors of multiple recurrence were fewer days (< 90) between episodes (aOR: 1.87 P< 0.01) and chronic renal disease (aOR: 1.59 , P< 0.01). Figure 1:Annual Incidence of CDI by age group.

A) Incidence of CDI among patients with only a single episode of CDI within 365 days. B) Incidence of CDI among patients with three or more episodes (two or more recurrence) within 365 days. RR documented compares 2016 to 2018 incidence in the 80+ age group

Conclusion

Time between 1st and 2nd CDI most strongly predicts likelihood of progression to multiple recurrences. Of all measured comorbid conditions, renal disease was most predictive. These findings may help to identify patients at high risk for progression for advanced interventions such as microbiota modifying therapies.

Disclosures

Scott Fridkin, MD, Pfizer: Grant/Research Support Colleen Kraft, MD MS, Rebiotix Inc: Advisor/Consultant|SERES: Advisor/Consultant.
476. Epidemiology and Outcomes of Candidemia in a Large Academic Medical Center
Authors: Pek Zachary , Bork Jacqueline T , Baddley John W
Published: December 2022

Background

Candidemia is an important cause of morbidity and mortality. Fluconazole resistance is associated with increased mortality in candidemia and thus echinocandins are recommended as first line empiric therapy. To understand the current landscape of candidemia treatment, we evaluated the epidemiology and outcomes of candidemia at our medical center, with a focus on differences in traditional azole-susceptible and non-susceptible candida species.

Methods

This is a retrospective cohort study including unique episodes of candidemia from 7/2017 – 12/2021 in hospitalized adult patients. We characterized candidemia episodes by species, age, hospital-onset, hospital location and critical illness. We compared traditionally azole susceptible organisms (e.g. C.albicans, C. parapsilosis, C.tropicalis) to non-susceptible (e.g. C.krusei, C.glabrata) based on antibiogram (cut off >94% susceptible) with the primary outcome of 30-day mortality. Secondary outcomes were recurrent/persistent candidemia, 90-day mortality and length of stay. Comparisons were done with χ2 or Wilcoxon rank sum tests. Logistic regression was performed to determine if azole-nonsusceptible candidemia was associated with 30-day mortality.

Results

404 candidemic episodes for 389 patients were identified, of which 72% were due to azole-susceptible Candida spp. and C.glabrata and C.krusei were 23% and 5%, respectively. Critically ill patients were more likely to have azole-non-susceptible Candida spp (59 vs. 48%, p=0.04). Overall 30-day mortality was 35%, and was similar between azole-susceptible and non-susceptible groups, with no difference in other outcomes (Table 1). After adjusting for age and hospital-onset, critically ill patients with azole-non-susceptible candidemia had odds ratio of 1.5 (95% CI 0.87 – 2.7 p=0.13) for 30-day mortality. Distribution of candida species and associated 30-day mortality are found in Table 2.

Demographics and Outcome

Distribution of most common Candida spp. in candidemia in critically ill (n=205)

Conclusion

We found similar 30-day mortality rates in azole-susceptible and non-susceptible candida species since echinocandin first-line empiric therapy was implemented in guidelines. The impact on critically ill and invasive infections, including ocular involvement, needs further evaluation.

Disclosures

All Authors: No reported disclosures.
501. Interferon-gamma Release Assays for Diagnosis of Latent TB Infection in Chronic Kidney Disease and Dialysis Patients
Authors: Hayuk Pattorn , Boongird Sarinya , Pornsuriyasak Prapaporn , Bruminhent Jackrapong
Published: December 2022

Background

Patients with chronic kidney disease (CKD), especially end-stage kidney disease (ESKD), are at risk of developing tuberculosis (TB). Due to their relatively immunosuppresses condition, reactivation from latent TB infection (LTBI) is the core pathogenesis in these populations. However, the prevalence of LTBI among Thai CKD patients, assessed by a high sensitivity and specificity test such as interferon-gamma release assay (IGRA), has never been thoroughly explored. We aimed to investigate the prevalence and predictors for LTBI among Thai CKD patients, including ESKD individuals receiving renal replacement therapy (RRT) either by hemodialysis (HD) or peritoneal dialysis (PD).

Methods

All CKD patients who underwent an investigation for LTBI status at Ramathibodi hospital were prospectively recruited from September 2020 to November 2021 and retrospectively reviewed from December 2020 to November 2021. Those with positive or borderline IGRA results using T SPOT®.TB without clinical or radiological findings compatible with active TB was diagnosed with LTBI. The LTBI prevalence was determined by CKD staging and type of dialysis. Predictors for LTBI were assessed by logistic regression analysis.

Results

A total of 199 CKD patients were enrolled; 102 prospectively and 97 retrospectively. There were 173 evaluable patients included with a mean (SD) age of 53 (16) years, and 44% were male. Of those, 95 (55%) had ESKD and maintained on RRT. Overall, 39 (22.5%) CKD patients had LTBI with the prevalence of 25%, 12.5%, 25%, 25% and 24.2% in those with CKD stage 1, 2, 3a, 3b and ESKD, respectively (p=0.89). Among ESKD patients, those who were maintained on HD had a higher proportion of LTBI than those on PD (28.9% vs. 5.3%, p=0.03). In multivariate analysis, drinking alcohol was significantly associated with LTBI (OR 8.51; [95%CI 1.24-58.38]; p=0.029), and HD therapy was marginally associated with LTBI (OR 8.14; [95%CI 0.95-69.91]; p=0.056) among ESKD patients.

Conclusion

In TB endemic settings, one-fifth of patients with CKD and a quarter of ESKD patients could carry LTBI status. Alcohol consumption and HD therapy could better identify high-risk ESKD patients and potentially screen for LBTI.

Disclosures

All Authors: No reported disclosures.
509. Role of cell-mediated immune monitoring using Interferon-γ Enzyme-linked Immunosorbent Spot Assay to predict CMV infection within six months after kidney transplantation
Authors: Namsiripongpan Warunyu , Kantachuvesiri Surasak , Bruminhent Jackrapong
Published: December 2022

Background

CMV infection can cause substantial morbidity and mortality in kidney transplant (KT) recipients due to an impairment in cell-mediated immunity (CMI) from immunosuppressive drugs. We investigated the role of CMI monitoring prior to and after transplant to predict CMV infection after KT.

Methods

A prospective study was performed between December 2020 and December 2021. All adult KT recipients underwent CMI measurement by investigating IFN-γ-producing T cells using enzyme-linked immunosorbent (ELISpot) assay before and one month post-transplant. The incidence of CMV infection within six months after transplant was reported, and predictors of CMV infection were analyzed using the Cox proportional hazard model.

Results

We included 93 KT recipients with a mean (SD) age of 44 (11) years; 59.1% were male, and 98.9% were CMV seropositivity. Twenty-two (23.7%) participants received anti-thymocyte globulin (ATG) for induction therapy. A median (IQR) of IFN-γ-producing T cells measured one month after transplant was significantly lower compared to before transplant (148 [54-389] vs. 763 [409-1,067] SFUs per 2.5 x 105 PBMCs, p < 0.001). Forty (42.9%) KT recipients who developed CMV infection appeared to have significantly less IFN-γ-producing T cells compared to those did not develop CMV infection (47.1%) (115 [33-237] vs. 238[76-492] SFUs/2.5x105 PBMCs, p=0.019). In univariate analysis, predictors for CMV infection included higher panel-reactive antibody (HR 1.02 [95%CI, 1.01-1.03], p< 0.001), receiving ATG for induction therapy (HR 3.45 [95%CI, 1.82-6.56], < 0.001) and lack of CMI one month after transplant defined as IFN-γ-producing T-cells of < 250 SFUs/2.5x105 PBMCs (HR 3.11 [95%CI, 1.36-7.10], p=0.007). In multivariate analysis, lack of CMI one month after transplant is the only predictor which remained independently associated with CMV infection (HR 3.1 [95%CI 1.2-7.80], p=0.019) (Table 1).

Conclusion

KT recipients with low IFN-γ-producing T cell responses are more likely to develop CMV infection post-transplant. Quantification of CMI using ELISpot assay could potentially predict those at risk of CMV infection after KT.

Disclosures

All Authors: No reported disclosures.
511. The cefazolin (CZ) and piperacillin-tazobactam (TZP) inoculum effects (IEs) are persistent amongst serial isolates of methicillin-sensitive Staphylococcus aureus (MSSA) derived from the sputum of persons with cystic fibrosis (pwCF) despite variation in other phenotypes.
Authors: Svishchuk Julianna , Waddell Barbara Jean M , Lee Sicheng , Rabin Harvey , Lisboa Luiz , Gregson Daniel , Surette Michael , Parkins Michael
Published: December 2022

Background

Phenotypic diversity among chronically infecting pathogens within the airways of pwCF is increasingly recognized, limiting susceptibility testing-directed decision-making (Somayaji, 2019, JCF). While it is an important outcome determinant in infection (Miller, 2018, OFID), the IE has generally only been studied in acute infection models. Herein, we sought to establish if variation in the presence of the IE to beta-lactams exists among CF-derived MSSA.

Methods

Single sputum cultures from 10 pwCF with chronic MSSA infection of ≥ 10 years in duration were collected, and 10 unique colonies from each were selected and confirmed as MSSA for a total of 100 isolates. Individual isolates were subjected to susceptibility testing at standard (SI: 105 CFU/mL) and high inoculum (HI: 107 CFU/mL) against CZ and TZP and assessed for protease (PRO) and hyaluronidase (HA) production in triplicate. The presence of the IE was defined if a ≥ 4-fold difference in MIC between SI and HI existed. All 100 strains were typed using pulsed-field gel electrophoresis.

Results

Patients included had a median age of 30.5 years, forced vital capacity of 93%, forced expiratory volume in one second of 66% predicted, and a BMI of 21.5 kg/m2. Median sputum MSSA burden was 106 CFU/ml. The IE was overall more common with TZP than CZ: 47% vs 33%, respectively. Median MIC50 for CZ increased between SI and HI: 0.5 to 1µg/mL, and TZP: 2 to 4µg/mL (p< 0.0001 for both). The most prevalent pulsotypes identified corresponded to multilocus sequence types (ST)-5 (20%), ST-30 (15%), and ST-1 (5%), where ST-30 isolates were more likely to exhibit the CZ and TZP IE (p< 0.0001 for both). Eight out of 10 patients had all isolates belonging to the same pulsogroup. Of patients infected with a single strain, discordance between IE phenotype was not noted, though PRO and HA production varied. Among these patients, the standard deviation of zone clearance diameter ranged from 0-0.9cm (mean range: 0-1.4cm) and 0-1.8cm (mean range: 0-7.2cm), respectively, between individual isolates.

Conclusion

Phenotypic diversity in chronic MSSA exists within the airways of pwCF. However, we observed the IE for CZ and TZP to be strain dependent, without variable penetrance.

Disclosures

All Authors: No reported disclosures.