bluuebunny/crossref_metadata_2025 huggingface dataset:
134. Characterization of circulating clinical multi-drug resistant and methicillin resistant Staphylococcus aureus isolates in Peru
Authors: Rojas Jesús D , Canal Enrique A , Bernal Manuela M , Lizewski Rhonda A , Rios Paul A
Published: December 2022

Background

Multi-drug resistant and methicillin resistant Staphylococcus aureus (MDR-SA and MRSA, respectively) constitute a significant threat to hospitalized patients. Surveillance for antibiotic resistance is needed in settings where over-the-counter antibiotic use is widespread to identify increasing antibiotic resistance that limits treatment options of nosocomial infections.

Methods

We performed phenotypic and genotypic characterizations of MDR-SA prospectively obtained from hospitals in Lima, Peru between 2015 - 2018. We collected 3103 bacterial isolates from clinical specimens. Bacterial samples were identified by conventional microbiology and BD Phoenix, and antimicrobial susceptibility testing (AST) was performed by disc diffusion, E-test and BD Phoenix. Additionally, multiplex PCR detected mecA, femA, and lukS in MDR-SA isolates. We selected 80 S. aureus isolates that were resistant to ≥ 3 antimicrobial classes and/or resistant to oxacillin or cefoxitin for genomic characterization using an Illumina NextSeq 500 sequencer.

Results

Testing identified 232/3103 isolates as S. aureus, and 80/232 (34%) isolates were MDR-SA, resistant to up to nine different antimicrobial classes. We observed high proportions of resistance to aminopenicillins 80/80 (100%), macrolides 71/80 (89%), lincomycins 69/80 (86%), quinolones 66/80 (83%), aminoglycosides 38/46 (82%). Notably, 75/80 (94%) isolates were MRSA. Interestingly, AST revealed that 81% had inducible resistance to clindamycin. In contrast, all isolates were susceptible to vancomycin, linezolid, and daptomycin. Multiplex PCR revealed that 5% of isolates carried the lukS gene and the mecA gene. 76 % of the isolates carried a bifunctional aminoglycoside modifying enzyme and a aminoglycoside O-nucleotidyltransferase enzymes that confer resistance to aminoglycosides. We detected the ermA gene in 79% of the isolates. In silico multilocus sequence typing (MLST) assigned the sequence type 5 to 91.2% MRSA isolates with multiple high related clusters observed, indicating the possibility of nosocomial dissemination and possible outbreak events.

Conclusion

Antibiotic pressure on the resistance patterns of S. aureus is evident in the high levels of resistance seen in these clinical isolates.

Disclosures

All Authors: No reported disclosures.
156. Using Whole Genome Sequencing to Genetically Profile and Analyze Escherichia coli Isolates with Varying Resistance to β-Lactam/β-lactamase Inhibitor Combinations
Authors: Marc Gohel , Amiji Hatim , Strope Benjamin , Sahasrabhojane Pranoti V , Greenberg David E , Shropshire William , Shelburne Samuel A
Published: December 2022

Background

Whole-genome sequencing has gained interest for assessing antimicrobial resistance (AMR). However, multiple studies have shown a poor correlation between the β-lactam/β-lactamase inhibitor (BL/BLI) phenotype and β-lactamase gene presence/absence. In a recent publication, we found that amplification of β-lactamase encoding genes potentially contribute to BL/BLI resistance and here we explore if gene amplifications allow for better BL/BLI genotype/phenotype correlations.

Methods

We selected 109 E. coli bacteremia isolates and performed ETests (bioMerieux, Inc) to determine AST profiles using the following BL/BLI antibiotics: ampicillin/sulbactam (SAM), amoxicillin/clavulanic acid (AMC), and piperacillin/tazobactam (TZP). CLSI M100 guidelines (2018) were used to stratify isolates into 4 groups: SAM/AMC/TZP susceptible (Group 1), SAM resistant only (Group 2), SAM/AMC resistant (Group 3), and SAM/AMC/TZP resistant (Group 4). Short-read whole genome sequencing was performed on these isolates and analyzed by identifying AMR genes, establishing multi-locus sequence type (MLST), estimating copy number variants (CNV), and investigating blaTEM-1 promoter regions in relation to phenotype. A t-Distributed Stochastic Neighbor Embedding (t-SNE) clustering method and a core-genome, maximum-likelihood phylogeny was generated to group isolates based on AMR gene content and CNV data.

Results

We found 34 different MLST groups with the three most common sequence types ST131 (n=41), ST1193 (n=12), and ST648 (n=6). Group 1 and Group 2 isolates had similar copy number estimates of β-lactamase blaTEM-1 (1.8X and 1.5X respectively) while there was an increase for both Group 3 (3.7X) and Group 4 (8.2X) isolates (Table 1). Additionally, blaOXA-1 was primarily present in Group 4 isolates (63%) with elevated copy numbers (5.2X). We did not observe associations of blaTEM-1 promoter regions with each of the BL/BLI Groups. Our t-SNE analysis shows that Group 1, Group 3, and Group 4 isolates cluster independently.

Core Genome Maximum-likelihood Phylogeny.

Midpoint-rooted core-genome maximum-likelihood phylogeny comparing core elements (MLST) to non core elements (CNV). AMR CNV and presence/absence associate better with BL/BLI phenotypes than do core elements.

Conclusion

There is a clear delineation between fully susceptible and fully resistant BL/BLI E. coli isolates when gene amplification and presence/absence of narrow-spectrum β-lactamases are considered, which should be considered for BL/BLI resistance prediction models.

Disclosures

David E. Greenberg, MD, Shionogi: Grant/Research Support.
157. A Survey of the Mid-South VA Healthcare Network on Ordering Practices and Interpretation of Procalcitonin
Authors: Eason Jane V , Bennett Jessica G , Byrd Jonathan , Callicott William , Thomas-Gosain Neena
Published: December 2022

Background

Procalcitonin (PCT) is an inflammatory biomarker that can be helpful for early detection of certain types of infections and can be a useful tool to decrease unnecessary antibiotic (abx ) exposure. However, its use among clinicians remains variable. The aim of this study was to elucidate current practices at a selection of Veteran’s Administration medical centers.

Methods

The VISN-9 Antimicrobial Stewardship Collaborative distributed a 15-question survey electronically to providers at all five VA medical centers in VISN-9 between 1/15/22 to 3/31/22 to clinicians practicing in the acute care, ICU and ED settings. Information on level of training, primary site as well as current practices and beliefs about PCT were collected. Responses were tabulated as percentages for this cross-sectional study.

Results

99 providers completed the survey with two centers comprising 83% of responses. 44% of respondents were attendings.

The Figures illustrate some interesting variability in the use of PCT. Figure 1 reveals more than half of residents but less than a quarter of attendings ordered PCT on admission for patients with suspected infection. Figure 2 shows similar use of PCT by attendings and residents to initiate abx, however, residents used PCT much more than attendings to justify continuation of abx, and residents used PCT somewhat more than attendings to de-escalate abx. Only one clinician ordered PCT daily. Figure 3, ordering practices by disease state, shows similar trends between the two groups.

44% of all respondents felt somewhat comfortable whereas 22% felt somewhat uncomfortable interpreting PCT results. Some of the interesting comments from respondents included: “PCT is “ordered too often and indiscriminately”; “I never know what to do with it”; and “I usually allow my patients to complete their abx courses rather than discontinuing abx earlier”.

Conclusion

Using PCT to help guide abx use can help minimize unnecessary abx exposure which may help to stem the increase in antimicrobial resistance. This survey indicates that many clinicians are unsure of when to use PCT, how often to order it, and whether it is a reliable enough tool on which to base treatment decisions. Further education will be necessary to help inform best practices.

Disclosures

All Authors: No reported disclosures.
181. Impact of Rapid Diagnostic Technology on Patients with Candidemia
Authors: Funderburk Patrick , Carr Amy L , Hayes Jillian E
Published: December 2022

Background

Candida spp. are the fourth most common cause of bloodstream infections (BSI) in the United States and have an associated mortality rate of 19-40.5%. Mortality rates are further impacted by delay in time to adequate antifungal therapy, historically due to delayed time to identification on culture. The utilization of rapid diagnostic technology (RDT) has been effective in timely identification of bacterial pathogens causing BSI, but RDT for fungal organisms has demonstrated mixed results. At AdventHealth Central Florida Division South (CFD-S), pharmacists provide 24-hour coverage for real-time notification of all positive blood culture results. The objective of this study was to evaluate the clinical impact of the GenMark ePlex Blood Culture Identification Panels (BCID) fungal pathogen (FP) panel paired with 24/7, pharmacist-driven response in patients with candidemia. 

Methods

This multi-site, pre/post, retrospective chart review included adult patients admitted to CFD-S with at least one positive blood culture with Candida spp. from June 2019 through May 2020 (pre-RDT), and August 2020 through July 2021 (post-RDT). Patients receiving systemic antifungal prophylaxis, with known candidiasis at time of index RDT result, or who discharged prior to culture positivity were excluded. The primary outcome was time to effective antifungal therapy in patients with candidemia.

Results

A total of 200 patients were included in the study (100 pre-RDT and 100 post-RDT). Overall, patients had a median age of 61 years and 50% were male. Patient characteristics are summarized in Table 1; median APACHEII score differed by three points (13.5 vs. 16.5). Time to effective therapy was similar between groups (39.8 vs. 38.5 hours, p=0.217). There was no difference in secondary outcomes (Table 2) other than ICU length of stay (2.5 vs. 6.0 days, p=0.033) and all-cause in-hospital mortality (15% vs. 30%, p=0.011).

Conclusion

Pharmacist-driven, real-time response to RDT did not significantly impact time to effective antifungal therapy in patients with candidemia. Higher rate of in-hospital mortality was likely a reflection of increased severity of illness in the post-RDT group.

Disclosures

Amy L. Carr, PharmD, BCIDP, Shionogi: Advisory Board.
186. Klebsiella aerogenes: Are there implications to taxonomic accuracy?
Authors: Herrera Lauren Nicholas , Brown Matthew L , Edwards William S , Leal Sixto M , Stripling Joshua , Lee Rachael A
Published: December 2022

Background

With advances in genomics, microbiologists can accurately rename existing bacteria which may cause confusion among clinicians familiar with prior names. Limited investigation is available on the clinical impact of these name changes. University of Alabama at Birmingham Hospital microbiology updated Klebsiella aerogenes in the electronic medical record (EMR) to "Klebsiella (Enterobacter) aerogenes" to reflect change in nomenclature. Therapy selection differs between Klebsiella pneumoniae and Enterobacter spp. due to differences in Ambler Class C (AmpC) beta-lactamase production. Our Antimicrobial Stewardship Program previously implemented selective and cascaded susceptibility reporting for E. aerogenes to guide antibiotic selection which remained after nomenclature change. The goal of this study is to determine if the change led to inappropriate antibiotic use.

Methods

We reviewed blood culture data from May 2016-2020 which grew Enterobacter aerogenes or Klebsiella "Enterobacter" aerogenes. We excluded polymicrobial blood cultures, patients aged 18 and under, and patients who died within 48 hours of drawing blood cultures. Appropriate therapy was defined as an antibiotic with reported susceptibility with consideration of AmpC induction for a duration appropriate to clinical syndrome with minimum of 7 days. We recorded patient demographics, nature of therapy, and clinical outcomes. We performed comparative analysis with descriptive statistics to compare the two groups.

Results

There were 38 patients with K. aerogenes bacteremia, 21 patients prior to name change and 17 afterwards. None were ESBL. Cefepime was most often used directed inpatient therapy while oral ciprofloxacin was the most common outpatient regimen with no use of ceftriaxone. Prior to name change, there was one case (4.76%) that did not receive targeted AmpC therapy while there were two afterwards (11.8%), one of which decided by the ID consult team. Table 1

Demographics (Data presented as No. (%)) Table 2

Microbiology and Outcomes (Data presented as No. (%)) Table 3

Antimicrobial Selection. One patient that received 72 hours of appropriate therapy but died prior to completion of therapy. This was labeled labelled as appropriate therapy.

Conclusion

Care must be taken when taxonomic changes of clinically relevant bacteria may potentially affect optimization of antibiotics. As the ID consultants, we must be aware of these name changes and provide up to date recommendations. Cascade reporting and documentation in the EMR may be helpful to reduce morbidity related to changes in nomenclature.

Disclosures

Sixto M. Leal, Jr., MD, PhD, GenMark Dx: Grant/Research Support|GenMark Dx: Honoraria.
198. The correlation of the genetic antibiotic resistance markers to antibiotic susceptibility testing (AST)
Authors: Morrison Caitlin , Pham Janis , Pearson Alicyn , King John , Lapp Noucas Heather S , Shivers Robert , Smith Roger
Published: December 2022

Background

Antibiotic resistant infections are a risk for increased patient mortality due to long time-to-results for current diagnostic methods. Results from a ∼1,500 patient trial demonstrated bacterial blood culture required 51 hours on average for a positive result. Current antibiotic susceptibility testing (AST) requires two additional days for phenotypic results. Studies show delays in effective treatment increases mortality rates by 7.6% every hour. The CDC classifies carbapenem-resistant Enterobacterales (13,000 annual deaths) as urgent threats, and vancomycin-resistant Enterococci and methicillin-resistant S. aureus (∼15,000 annual deaths combined) as serious threats. Identifying resistance markers direct from patient samples may aid clinical decisions, reduce antibiotic use, reduce time to effective therapy, and improve patient outcomes

Methods

200 antibiotic resistant bacterial strains were genotyped for 13 clinically-relevant resistance genes and screened for antibiotic resistance phenotypes. Results identified correlations between resistance markers and phenotypic resistance and potential aid for clinical treatment.

Results

High resistance to vancomycin and piperacillin-tazobactam, first-line antibiotics, were seen in 48 Gram-positive and 69 Gram-negative strains. Presence of Gram-positive markers vanA or vanB correlated to 100% (28/28) vancomycin resistance and 88% (25/28) ampicillin resistance. In 85 sequenced Gram-negative strains, 35 harbored metallo-β-lactamase (blaIMP,blaNDM,blaVIM), 35 contained extended spectrum β-lactamase (blaCTX-M-14,blaCTX-M-15), 21 contained AmpC β-lactamase (blaDHA,blaCMY), and 34 contained carbapenenase (blaKPC,blaOXA48). These markers correlated to 100% resistance to ampicillin, cefazolin, and cefuroxime in all strains.

Conclusion

Together, these data suggest that molecular diagnostics that identify genetic markers may provide clinicians with needed information during a window when therapeutic intervention can improve patient outcomes.

Disclosures

Caitlin Morrison, B.S., T2 Biosystems: Stocks/Bonds Janis Pham, B.S., T2 Biosystems: Stocks/Bonds Alicyn Pearson, PhD, T2 Biosystems: Stocks/Bonds John King, B.S., T2 Biosystems: Stocks/Bonds Heather S. Lapp Noucas, MSc, T2 Biosystems: Stocks/Bonds Robert Shivers, PhD, T2 Biosystems: US20200291488A1|T2 Biosystems: Stocks/Bonds Roger Smith, Ph.D., T2 Biosystems, Inc: US20180188195A1, EP3849938A1,WO2020257691A1, WO2020252084A1|T2 Biosystems, Inc: Stocks/Bonds.
203. When rapid molecular blood culture testing fails to identify the organism: microbiology and patient outcomes
Authors: Marshall MaryBeth , Kale-Pradhan Pramodini , Hejnar Anna , Smith Evelynne , Giuliano Christopher , Harriott Melphine , Priziola Jennifer , Johnson Leonard B
Published: December 2022

Background

Verigene™ is a rapid nucleic acid test used to optimize antibiotic selection on positive blood cultures but it does not detect all pathogens. The purpose of this project was to describe the organisms Verigene™ could not identify as well as the clinical outcomes of the patients.

Methods

This was a single-center, retrospective cohort study of patients who received a Verigene™ non-detected result from 5/19/20-6/30/21. The primary objective of this study was to identify the organisms and secondary objectives included any changes in antimicrobial therapy after the test result, appropriateness of change in therapy, discharge disposition, and 30-day readmission rate.

Results

A total of 85 of 958 (8.9%) Verigene results were non-detected during the time period. Among the 85 results included for the primary objective, six were determined to be contaminants by the clinicians. Among the remaining 79 results, 44 were anaerobic bacteria, 11 Serratia species, and 24 were other miscellaneous bacteria. Therapy was changed in 62 (78.5%) after the Verigene result. Overall antibiotic regimens were deemed appropriate after antibiotic changes were made from the final culture result in 70 of 79 (88.6%) cases. Twenty five of 79 (31.6%) patients died in the hospital. Among the 54 patients discharged, 11 (20.3%) were readmitted within 30 days including five (9.2%) due to infection. No cases of infectious readmission were due to the prior episode of bacteremia.

Conclusion

The majority of Verigene results that were not able to be identified were later identified to be anaerobic bacteria and Serratia species which are known limitations of the test. While most patients received appropriate therapy, there was a high mortality and readmission rate. Further studies should be performed to confirm this observation.

Disclosures

All Authors: No reported disclosures.
208. Clinical outcomes of empirical versus pre-emptive broad spectrum antifungal therapy in patients with acute myelogenous leukemia receiving antimold prophylaxis
Authors: Oh Sang-Min , Lee Chan Mi , Choi Seong Jin , Lee Eunyoung , Kang Chang Kyung , Moon Song Mi , Choe Pyoeng Gyun , Song Kyoung-Ho , Park Wan Beom , Bang Ji Hwan , Kim Eu Suk , Park Sang Won , Kim Hong Bin , Kim In Ho , Kim Nam Joong , Oh Myoung-don
Published: December 2022

Background

Since antimold prophylaxis has been widely used in induction chemotherapy for acute myelogenous leukemia (AML), it should be re-evaluated whether broad spectrum antifungal therapy should be empirically used in prolonged febrile neutropenia. Therefore, we compared clinical outcomes of empirical versus pre-emptive antifungal therapy in patients with AML receiving antimold prophylaxis.

Methods

From September 2016 to December 2020, all adult AML patients (≥ 18 years) receiving antimold prophylaxis who had febrile neutropenia for ≥ 4 days during induction or re-induction chemotherapy at Seoul National University Hospital were retrospectively reviewed. They were classified into the empirical group (therapeutic broad spectrum antifungal agents had been used without evidence of invasive fungal infection [IFI]) or the pre-emptive group (antimold prophylaxis had been maintained until the emergence of IFI’s evidence). We compared clinical outcomes between the two groups after propensity score matching.

Results

A total of 229 chemotherapy episodes, 36 in the empirical group and 193 in the pre-emptive group, were analyzed. In the pre-emptive group, broad spectrum antifungal therapy was administered in 45 (23.3%) episodes. After 1:3 matching with age, gender, induction or re-induction chemotherapy, and worst qSOFA score at febrile neutropenia, incidence of proven or probable IFI (0/36 [0%] in the empirical group vs. 5/97 [5.2%] in the pre-emptive group, P=0.323) and all-cause mortality (3/36 [8.3%] in the empirical group vs. 4/97 [4.1%] in the pre-emptive group, P=0.388) were not different between the two groups.

Conclusion

Clinical outcomes of empirical versus pre-emptive broad spectrum antifungal therapy were comparable in patients with AML receiving antimold prophylaxis. Broad spectrum antifungal therapy could be delayed until the emergence of evidence of IFI, in the current era of antimold prophylaxis.

Disclosures

All Authors: No reported disclosures.
213. Prophylactic oral vancomycin for Clostridioides difficile in allogeneic hematopoietic stem cell transplant recipients
Authors: Ogawa Lauren , Wright Kaylor , Luk Alfred
Published: December 2022

Background

Allogeneic hematopoietic stem cell transplant (alloHSCT) recipients are at substantial risk for Clostridioides difficile infection (CDI) due to prolonged hospitalization and alteration of the intestinal mucosa and gut microbiota from conditioning regimens, antimicrobials, and immunosuppressants. CDI in alloHSCT recipients has also been associated with higher rates of acute graft versus host disease (aGVHD). Review of the literature revealed that three institutions have published studies demonstrating oral vancomycin prophylaxis prevents CDI. However, more studies are needed to evaluate the impact of prophylaxis on CDI incidence, resistant infections, and other transplant-related outcomes.

Methods

We conducted a retrospective review to compare the effectiveness of prophylactic oral vancomycin versus no prophylaxis in 40 alloHSCT recipients in the prevention of CDI at our institution. The prophylactic intervention was initiated June 2020, and 20 patients have undergone alloHSCT as of April 2022. Patients received twice daily oral vancomycin starting the day of admission for transplant until discharge. The prophylaxis group was compared to a control group of 20 consecutive alloHSCT recipients prior to initiation of the intervention. The primary outcome was the incidence of CDI. Secondary outcomes included incidence of vancomycin resistant enterococcus (VRE) infection and incidence of aGVHD.

Results

During admission for transplant and at +100 days post-transplant, 5/20 (25%) of patients in the control group developed CDI compared to 0/20 (0%) in the prophylaxis group (p=0.0471). Prophylaxis was not associated with higher rates of VRE infection through day +100 post-transplant (2/20, 10% vs 0/20, 0%, p=0.487). Use of oral vancomycin was not associated with increased incidence of aGVHD, which occurred in 10/20 (50%) of patients in the control group versus (7/20) 35% in the prophylaxis group (p=0.523).

Conclusion

Prophylaxis with oral vancomycin was associated with a significant reduction in CDI. Use of prophylaxis was not associated with an increased risk for VRE infection and there was no change in incidence of aGVHD. Our review supports the use of prophylaxis, and we will continue to monitor for resistant infections and evaluate the impact on survival.

Disclosures

Alfred Luk, MD, Karius: Grant/Research Support.
224. Effect of a Mobile App Chatbot and an Interactive Small Group Webinar on COVID-19 Vaccine Intention and Confidence in Japan: A Randomized Clinical Trial
Authors: Yamada Yuji , Tomoi Hana , Nishina Yuka , Harada Ko , Tanaka Kyuto , Sasaki Shugo , Inaba Kanako , Mitaka Hayato , Takahashi Hiromizu , Passanante Aly , Lin Leesa , Lau Eric , Wu Joseph , Naito Toshio , Larson Heidi , Kobayashi Takaaki
Published: December 2022

Background

Little is known about how social media platforms can be used to increase COVID-19 vaccine intent. We aimed to investigate the effect of social media-based interventions on vaccine hesitancy in Japan.

Methods

We conducted a three-arm randomized controlled trial between 5 November 2021 and 9 January 2022. Japanese aged 20 or above who had not received any COVID-19 vaccine and did not intend to be vaccinated were randomly assigned to one of the following three groups: (i) a control group (with no intervention), (ii) a group with a free chatbot in a popular messenger app called ‘LINE,’ which provided general information on COVID-19 vaccines and (iii) a group with free webinars where healthcare professionals interactively provided participants with the information on COVID-19 vaccines. The vaccine intention (VI) and three pre-defined Vaccine Confidence Index (VCI), including the importance, safety, and effectiveness of COVID-19 vaccines, were compared.

Results

1,158 persons were included, and the baseline characteristics and demographics were balanced across three groups (Table 1). Among 386 persons assigned to the chatbot group, 231 (59.8%) accessed the chatbot and answered the post-survey. The post-survey revealed no significant difference in VI or VCI between the chatbot group and the control group (Table 2). Among 386 persons assigned to the webinar group, 207 (53.6%) attended webinars and answered the post-survey. The post-survey revealed no difference in VI between the webinar group and the control group. However, the VCI for the importance and the effectiveness significantly increased in the webinar group. There was no difference in VCI for the safety. VCI for the importance and the effectiveness in the control group decreased without any intervention during the study period.

Vaccine intention and confidence after interventions Table 1Table 2

Conclusion

While this study demonstrated that neither the chatbot nor the webinar changed VI, VCI for the importance and the effectiveness significantly increased with the webinar intervention. Interactive webinars with live Q and A provided by professionals may have a role in increasing COVID-19 vaccine confidence. Given the degree of vaccine hesitancy worsened over time in the control group, timely intervention is required.

Disclosures

All Authors: No reported disclosures.
261. COVID-19 and Diabetes Mellitus: Glycemic Control and Risk Factors for Mortality, experience from Pakistan.
Authors: Nasim Asma , Kumar Sunil
Published: December 2022

Background

Diabetes mellitus (DM) is a chronic disease characterized by glucose dysregulation by insulin deficiency or resistance. DM is one of the risk factors and found to be associated with high mortality in patients with corona virus disease-19 (Covid-19). There are challenges in managing poorly controlled DM among Covid-19 patients. Our aim is to highlight the effect of Covid-19 and DM on each other by studying glycemic control and risk factors for mortality.

Methods

This study is a single center retrospective observational review from Pakistan. Covid-19 diagnosed patients admitted during the months of March 2020 to March 2021were included. The patients were divided into DM and non-DM. Demographics, clinical variables and outcome were collected and compared between these groups. Glycemic control during hospitalization (blood sugar level fasting and pre-meal twice a day) was noted. Fasting glucose level >120 mg/dl, and random >200 mg/dl were considered as poor glycemic control. Survivors and non- survivors among DM patients were compared.

Results

A total of 366 patients were included in this study, 113(30.87%) were DM and 253(69.12%) were non-DM. Mean age was comparable in two groups, however, patients in DM group were older (age >45 years, p=value 0.039). Significantly more patients with hypertension (p value< 0.001) and ischemic heart disease (p value< 0.001) developed Covid-19 in DM group. There was no difference in mortality among both groups (p=0.29). (Table 1) .In DM patients, the significant risk factors for mortality were age >60years, hypertension and renal disease. High fasting and pre-dinner blood glucose levels (mean) obtained at admission and day 5 were significantly associated with mortality. (Table2).

Conclusion

Diabetic patients with advanced age and concomitant other comorbid conditions is associated with increased risk of death. In diabetic patients, more attention should be focus on dynamic monitoring and strict glycemic control as severe COVID 19 infection and its treatment with steroids can have a negative impact on outcome.

Disclosures

All Authors: No reported disclosures.
277. Frequency of Pneumomediastinum and Pneumothorax in COVID-19 Patients: a Retrospective Cohort Study in a Community Hospital in Evanston, Illinois
Authors: Egoryan Goar , Nava Guillermo Rodriguez , Nava Guillermo Rodriguez , Kishmiryan Armen
Published: December 2022

Background

Pulmonary barotrauma has been increasingly reported as a complication of COVID-19. Although a rare phenomenon, pneumomediastinum has been shown to be more prevalent in COVID-19 patients than in historical patients with adult respiratory distress syndrome.

Methods

We performed a Workbench report to identify 1046 patients admitted to our community hospital in Evanston, Illinois, with a primary diagnosis of COVID-19 from March 1, 2020, to January 31, 2022. Descriptive statistics were used to summarize the data.

Results

The incidence proportion risk was 3.15%. The median age was 66 years (interquartile range [IQR], 49.5 – 75.5 years), 84.8% (28/33) were males, 24.2% (8/33) were Asian, 18.2% (6/33) were White, 18.2% (6/33) were Latinx, and 9.1% (3/33) were long-term care facility residents. Pneumothorax was present in 21 patients (63.6%): unilateral 18/21 (54.5%); bilateral 3/21 (9.1%). Pneumomediastinum was present in 22 patients (66.7%). The median onset time of pneumothorax or pneumomediastinum after COVID-19 onset was 18 days (IQR, 11.5 – 25.5 days). Among 28 (84.8%) patients that required invasive mechanical ventilation (IMV), 6 (18.2%) developed pneumothorax or pneumomediastinum prior IMV; 5 (15.2%) patients developed pneumothorax or pneumomediastinum without IMV. The median onset time of pneumothorax or pneumomediastinum after IMV was 4 days (IQR, 0 – 8 days). Only 4 (9.1%) patients were ultimately discharged, 24 (72.7%) died, 2 (6.1%) were transitioned to hospice care, 3 (9.1%) were transferred to long-term care acute care, and 1 (3%) patient was transferred for ECMO. The fatality rate was higher compared to case reports available in the literature (5/23, 21.7% fatality rate. Table 1).

Available data in the literature per case reports of pneumomediastinum and pneumothorax in COVID-19 patients

Abbreviations: A-fib, atrial fibrillation; CAD, coronary artery disease; CPAP, continuous positive airway pressure, DM, type 2 diabetes; F, female; HLD, hyperlipidemia; HTN, hypertension; IMV, invasive mechanical ventilation; M, male; NC, nasal cannula; NIV, non-invasive ventilation; NRB, non-rebreather mask; OSA; obstructive sleep apnea; PMD, pneumomediastinum; PTX, pneumothorax; yo, years old.

Conclusion

The practitioners have to be alerted of the association of COVID-19 with pneumomediastinum, especially on the fact that this complication may happen in patients who never received mechanical ventilation or positive airway pressure support. Further research is needed into the exact pathogenesis, prevalence of this complication, and the impact on the clinical outcomes.

Disclosures

All Authors: No reported disclosures.
279. Maternal Infection by SARS CoV2 and Clinical Repercussion of the Newborn.
Authors: Casillas Casillas Maria C , Lopez-Enriquez Claudia C , Madrid Tania Salcido
Published: December 2022

Background

Pregnancy confers a higher risk of complications in SARS CoV2 disease as well as in the neonatal stage. Physiological and immunological changes during pregnancy predispose women to have complications in all the respiratory variations and increase maternal-fetal mortality and morbidity; The role of SARS CoV2 infection in newborns of mothers positive for COVID-19 was evaluated, analyzing the clinical consequences in the pregnant patient and the impact on the newborn.

Methods

Descriptive, observational, retrospective study. All pregnant patients with a positive PCR test for SARS CoV2 and newborns treated at the Spanish Hospital, in the period from March 2020 to March 2021, were included, the information provided was collected from the medical history.

Results

We recorded the cases of pregnant patients treated at the Spanish Hospital in the period from March 2020 to March 2021. The population was divided into those with a positive and negative PCR test for SARS Cov2. A total of 561 cases were registered, 35 positive cases for SARS Cov2; positive patients reported a higher presentation of Preeclampsia than patients without infection (p 0.009). The percentage of preterm products in mothers with infection was higher by 20% vs 12%; with the highest number of advanced neonatal resuscitation events. SARS Cov2 infection conditions the presentation of pathologies such as preeclampsia in pregnant women and an increase in preterm birth.

Conclusion

In this study we conclude, comparing with the group of healthy pregnant women with no history of COVID-19, that the products of mothers with a history of SARS CoV2 infection represent a higher risk of prematurity coupled with the risk of other pathologies such as preeclampsia, also in the period neonatal patients required greater support with oxygen, however the rate of severe complications in the newborn is unlikely. The role of maternal protection such as isolation, hygiene and vaccination measures are priority tools to reduce these perinatal pathologies and the risk of contagion.

Disclosures

All Authors: No reported disclosures.
280. Monoclonal Antibodies Against SARS-CoV-2 in Fragile Outpatients: Clinical and Laboratory Risk Factors and Protective Role of Vaccination
Authors: Cavasio Rosario Alessandro , Braccialarghe Neva , Zaçe Drieda , Spalliera Ilaria , Coppola Luigi , Campogiani Laura , Piermatteo Lorenzo , Bellocchi Maria Concetta , Silberstein Francesca Ceccherini , Marco Iannetta , Sarmati Loredana , Andreoni Massimo
Published: December 2022

Background

To cope with the SARS-CoV-2 pandemic, several treatments were studied and out of these, monoclonal antibodies (MAbs) have shown efficacy to prevent the development of pneumonia after the infection

Methods

We conducted a retrospective, single-center study including patients with SARS-CoV-2 infection, treated with MAbs (bamlanivimab/etesevimab (B/E), casirivimab/imdevimab (C/I) or sotrovimab (S)) from March 2021 to February 2022

Results

We included 504 patients with a median age of 62 years (IQR 49-72), 51% were males and 66% had completed the vaccination schedule according to the current Italian regulations. The most frequent eligibility criteria are summarized in figure 1. As for MAbs combination, patients were treated with B/E (54%), followed by C/I (30%) and S (16%). Outcomes are shown in Table 1.

Nasopharyngeal swab (NPS) negativization time had a positive correlation with patients’ age (r=0.16; p=0.001), C-reactive protein (CRP) (r=0.26; p< 0.001) and creatinine values (r=0.22; p< 0.001) assessed at baseline (infusion day). Time to NPS negativization was 6.9 (95% C.I. [4.5-9.2]) days shorter for vaccinated compared to unvaccinated patients (p< 0.001).

Patients treated with C/I had a negative NPS on average 4.5 (95% C.I.= [1.8-7.3] days earlier than patients treated with B/E; patients who received S reached negativization 6.0 (95% C.I.= [2.2, 9.9]) days earlier than those treated with B/E (p=0.004). Patients with positive outcome had a negative NPS on average 14.3 (95% C.I.= [6.8, 23.1)], 25.5 (95% C.I.= [18.9, 33.4] and 68.3 (95% C.I.= [47.7, 90.2]) days earlier than patients who needed hospitalization and patients who died (p< 0.001, p< 0.001, respectively).

Unvaccinated patients had a higher rate of oxygen support need compared to vaccinated ones (p=0.006). Patients with worse outcomes were significantly older and had higher values of CRP and creatinine at baseline (p=0.04, p< 0.001, p< 0.001, respectively)

Percentage of eligibility criteria of our patients

The majority of patients had more than one criterion

Clinical outcome of our patients

Nasopharyngeal swab was repeated weekly, until negative

Conclusion

MAbs reduce the risk of hospitalization in fragile patients. Vaccinated patients had shorter time of NPS negativization and lower probability of hospitalization. Older age, higher CRP and creatinine values assessed at baseline, correlated with worse outcomes. S was the most effective treatment amongst MAbs used in our study

Disclosures

All Authors: No reported disclosures.
284. Post-Acute Sequelae of COVID-19 Two Years After Acute Infection
Authors: Logue Jennifer , Franko Nicholas M , Kemp Megan M , McCulloch Denise J , Chow Eric J , Chu Helen Y
Published: December 2022

Background

The post-acute sequelae of COVID-19 (PASC) includes a constellation of debilitating symptoms after SARS-CoV-2 infection. Much remains unknown about the long-term health burden of COVID-19. We describe the symptom course and quality of life of adults up to 2 years after mild acute COVID-19.

Methods

Adults within 30 days of laboratory-confirmed acute COVID-19 were enrolled as cases from January – September 2020 and followed for 2 years. Demographic and symptom data were collected in an enrollment survey and at 6, 12 and 24 months post-infection. Surveys included vaccination status, symptom course, and quality of life assessments (Fatigue Assessment Scale (FAS) and EuroQual visual analog scale (VAS)). A cohort of SARS-CoV-2 uninfected controls was concurrently enrolled and surveyed. We used descriptive statistics to compare cases and controls and defined a p-value < 0.05 as significant.

Results

A total of 112 of 239 enrolled cases and 44 of 59 controls completed all surveys. Of the 112 cases, 105 (94%) had mild disease. In the 6, 12 and 24 month surveys, 39 (35%), 48 (43%) and 56 (50%) cases indicated at least one persistent symptom, respectively, compared to 4 (9%), 5 (11%) and 6 (14%) controls (Table 1). In all 3 surveys, fatigue and altered smell or taste were the most common post-infection symptoms among cases (Figure 1). At 2 years, 40 (36%) cases reported symptoms were improving or resolved and 30 (27%) reported symptoms continued to wax and wane. Symptoms improved and worsened for 10 and 4 cases, respectively, following a complete SARS-CoV-2 vaccination. 46% reported seeking medical attention for persistent symptoms and 34% of those employed reported symptoms negatively impacted their ability to work. When compared to controls in the 12 and 24 month surveys, cases had a significantly higher mean FAS score (p-value < 0.001 and 0.01, respectively) and significantly lower VAS score (p-value = 0.01 and < 0.001, respectively).

Demographic and Clinical Characteristics of the Study Cohort

a. Time since symptom onset in infected cohort and time since enrollment in healthy controls

b. Other race/ethnicity included American Indian or Alaska Native, Black or African American, Native Hawaiian or other Pacific Islander, and more than 1 race.

Percentage of participants reporting symptoms at 6-, 12-, and 24-months

*

Conclusion

Symptoms associated with PASC were reported up to 2 years after infection with significant impacts on quality of life. These findings underscore the healthcare and societal burdens even after recovery from acute infection. As studies seek to identify the underlying mechanisms of PASC, prevention of acute infection remains the mainstay of COVID-19 burden mitigation.

Disclosures

Helen Y. Chu, MD, MPH, Cepheid: Reagents|Ellume: Advisor/Consultant|Gates Ventures: Grant/Research Support|Merck: Advisor/Consultant|Pfizer: Advisor/Consultant.
288. Prognostic Factors for In-hospital Mortality of Patients with Severe COVID-19 Hospitalized in the University Medical Center, Lithuania
Authors: Kubiliute Ieva , Urboniene Jurgita , Rudenaite Akvile , Zablockiene Birute , Gefenaite Giedre , Jancoriene Ligita
Published: December 2022

Background

Till May 2022 there were 1.06 million of COVID-19 cases and 9108 deaths caused by COVID-19 disease registered in Lithuania. The objective of the study was to evaluate prognostic factors for in-hospital mortality of patients with severe COVID-19 disease.

Methods

COVID-19 positive adult patients hospitalized in Vilnius University Hospital Santaros Klinikos, Lithuania, were included in the cohort study between March 2020 and December 2021. Medical history, vital signs were collected, laboratory tests, chest X-ray were performed. Severe COVID-19 disease was defined as pneumonia with objective respiratory failure symptoms. ROC curve was used to evaluate prognostic value of a laboratory test, multivariable logistic regression was used to determine the prognostic factors for in-hospital lethal outcome. p-value < 0.05 was considered significant.

Results

Severe COVID-19 disease was diagnosed for 291 participants, 21 (7.2%) of them died. Hematological, lung diseases and cancer were more common among patients who died compared to those who recovered (Table 1). Patients who died were older, more frequently had confusion (25.0% vs 5.2%, p=0.001), tachypnea (57.1% vs 26.7%, p=0.003), and dyspnea (81.0% vs 54.1%, p=0.017), their time median from symptoms onset to admission was shorter (2.5 (IQR 0-7) vs 7 (IQR 4-9) days, p< 0.001) compared those who recovered. On admission, patients who died had lower lymphocytes count, higher neutrophiles count and higher concentration of aspartate aminotransferase (AST), lactate, creatinine and urea compared to those who recovered. The best prognostic features for lethal outcome possessed neutrophiles count, AST, lactate, creatinine and urea (Figure 1). Optimal cut-off values were calculated and included into multivariable regression model. Multivariable regression revealed that hematological diseases (OR 8.68; 95% CI 1.46-51.40, p=0.017), initial AST > 32.9 U/l (OR 13.57; 95% CI 1.46-125.94, p=0.022), lactate > 1.46 mmol/l (OR 4.87; 95% CI 1.03-22.86, p=0.045) were associated with in-hospital mortality of patients with severe COVID-19 adjusted for age.

Conclusion

Hematological diseases, elevated AST and lactate are significant prognostic factors for in-hospital mortality of patients with severe COVID-19 disease at earlier stages of disease.

Disclosures

All Authors: No reported disclosures.
290. Quantitative Antibody Levels Against SARS-CoV-2 Spike Protein in Children with COVID-19 and MIS-C
Authors: Avcu Gulhadiye , Arslan Sema Yıldırım , Soylu Mehmet , Bilen Melis , Çiçek Candan , Bal Zümrüt Şahbudak , Kurugöl Nuri Zafer , Ozkinay Ferda
Published: December 2022

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has different clinical courses in children and adults. The majority of coronavirus diseases 2019 (COVID-19) caused by SARS-CoV-2 are either mild or asymptomatic in children.

This report aimed to determine quantitative antibody levels against SARS-CoV-2 spike protein in children with COVID-19 and MIS-C.

Methods

A single-center retrospective study was conducted at a tertiary-level university hospital. Seventy-five pediatric patients diagnosed with COVID-19 and MIS-C were included between September 2021 and February 2022.

The demographic, clinical and laboratory data of cases were extracted from medical records. The duration of hospitalization, management, and outcomes was reported.

Quantitative antibody levels against SARS-CoV-2 spike protein in the third month after the initial diagnosis was measured, and patients were also evaluated for post-COVID-19 syndrome symptoms .

Results

The patients were categorized into three disease phenotypes; there were 36 (48%) patients with mild/asymptomatic (group1)( M/F 20/16, mean age, 11.4 years) 22 (29.3%) patients with moderate to severe SARS-CoV-2 infection (group 2)(M/F 13/9, mean age, 13 years) and 17 (22.6%) patients with MIS-C (group 3)( M/F 9/8, mean age, 10.1 years).

The majority of the children in group 1 (80.6%), in group 2(90.9%), and in group 3(82.4%) had a detectable IgG antibodies to SARS-CoV-2 spike protein(p=0.567). The mean antibody values against SARS-CoV-2 spike protein was 321.9±411.6 in group 1, 274±261 in group 2, and 220±299 in group 3 (p >0.05).

The antibody positivity rate was similar in patients with COVID-19(85.5%) and MIS-C (82.4%) (p=0.833). The mean antibody value against SARS-CoV-2 spike protein was 303.9±360.3 in the COVID-19 group and 220 ±299 in the MIS-C group(p >0.05).

Conclusion

The majority of the children had a detectable IgG antibody level to SARS-CoV-2 spike protein. There was no difference between asymptomatic/mild disease, moderate/severe disease, and MIS-C groups in mean antibody levels. Long-term studies are needed to examine antibody responses over time in children with COVID-19 and MIS-C for different vaccination schedules.

Disclosures

All Authors: No reported disclosures.
309. Genetic Diversity and Conservation of Envelope Gene of SARS-CoV-2 and its Variants B.1.1.7, B.1.351, P.1, B.1.617.2 and B.1.1.529 with comparison with other human coronaviruses
Authors: Liu Benjamin
Published: December 2022

Background

SARS-CoV-2 E gene PCRs have been widely used as the first-line assay with a higher sensitivity than those targeting N or RdRp gene. Given the currently available primers and probes were designed at the onset of the pandemic, it is unknown whether the SARS-CoV-2 VOCs have accumulated significant mutations that may affect E gene PCRs. In this study we aim to perform a comprehensive genetic analysis of SARS-CoV-2 E gene sequences to evaluate the impact of the emerging VOCs on E gene PCR performance.

Methods

600 whole-genome sequences of 7 species of human coronaviruses (HCoVs) were retrieved from GenBank and GISAID, including Sarbecoviruses (SARS-CoV-2 variants B1.1.7, B1.351, P.1, B.1.617.2 and B.1.1.529, and SARS-CoV), Embecovirus (OC43, HKU1), Merbecovirus (MERS) and Alphacoronaviruses (229E, NL63). The E gene sequences were retrieved from full-length genomes of corresponding viruses and aligned by ClustalW multiple alignment. Phylogenetic, conservation and mutation analyses analysis of the enrolled sequences was performed.

Results

E gene-based phylogenetic analysis yielded HCoVs typing results consistent with whole genome typing, suggesting E gene is a reliable locus for phylogenetic analysis and typing of HCoVs. Four pan-Sarbecovirus conserved E gene regions were identified with 100% conserved nucleotide similarity among SARS-CoV-2 and its VOCs, as well as SARS-CoV. These regions have appropriate G/C content which may be suitable for primer/probe design for E gene-based pan-Sarbecovirus screening assay. No significant E mutations were found in 137 retrieved SARS-CoV-2 and its VOCs. Interestingly, two novel variations, C26299U and T26354A, were identified in two of our SARS-CoV-2 strains. The latter variation occurred at the 3’ end of the target region of the widely used Charité/Berlin (WHO) probe. This variant may lead to a potential failure of the first-line E gene PCR.

Conclusion

Our data shed light on the genetic diversity and conservation of E gene of SARS-CoV-2 and may be beneficial for future primer/probe design for novel first-line assay or SARS-CoV-2-specific E gene PCR. SARS-CoV-2 VOCs have not accumulated significant mutations in E gene so far. The impact of novel E gene variations C26299U and T26354A on molecular diagnostic testing warrants further investigation.

Disclosures

All Authors: No reported disclosures.