bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt; 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 ( &gt;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

Abstract

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

Abstract

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 (&gt;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&lt; 0.01). Multiple recurrent CDI decreased 45% from 9/100,000 to 5/100,000) (P&lt; 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&lt; 0.01).. Independent predictors of multiple recurrence were fewer days (&lt; 90) between episodes (aOR: 1.87 P&lt; 0.01) and chronic renal disease (aOR: 1.59 , P&lt; 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

Abstract

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 &gt;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

Abstract

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

Abstract

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 &lt; 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&lt; 0.001), receiving ATG for induction therapy (HR 3.45 [95%CI, 1.82-6.56], &lt; 0.001) and lack of CMI one month after transplant defined as IFN-γ-producing T-cells of &lt; 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.