bluuebunny/crossref_metadata_2025_split huggingface dataset:
289. Prolonged Corticosteroid Usage, Associated Infectious Complications, and High Mortality in Adult Patients with COVID-19
Authors: Chu Rebecca , Zafonte Veronica B , Cervellione Kelly L , Miele Andrew S , Bagheri Farshad , Shakil Javeria 
Published: December 2022

Abstract

Background
Based on the RECOVERY trial, the NIH strongly recommends systemic corticosteroids for COVID-19 pneumonia with hypoxia. The study demonstrated reduced 28-day mortality after dexamethasone 6mg daily for up to 10 days compared to SOC alone. In practice, physicians may continue therapy for longer periods if potential benefit outweighs potential risk. Little is known about adverse events associated with prolonged corticosteroid use in patients with COVID-19; however, in general, this can increase risk for bacterial or fungal infections. This study aimed to explore the incidence of secondary infections during extended corticosteroid use for COVID-19.

Methods
A retrospective study was performed in adults at two community hospitals between September 2020 and May 2021 with a diagnosis of respiratory failure secondary to COVID-19 infection. Those with at least one new, laboratory-confirmed secondary infection during hospitalization after at least 10 cumulative days of corticosteroids were included. Demographic characteristics, clinical data and outcomes were extracted from the medical records. Quantitative analyses was performed using SPSS v27.0 and R.

Results
Of over 1,500 COVID-19 admissions within the timeframe, 73 patients met inclusion criteria (Table 1). No patient received immunomodulators for COVID-19 treatment. Patients had a median of 18 days on corticosteroids (range 10-65 days) prior to first positive culture. There were 130 positive cultures identified in blood, urine, and sputum samples (Figure 1), including polymicrobical cultures, yielding 34 clinically relevant organisms (Table 2). Hospital course was complicated by septic shock (68.5%), worsening of lung function (76.7%), and acute organ damage (57.5%); 55 (75%) patients expired during index admission.

Conclusion
Patients with COVID-19 on extended courses of corticosteroids have relatively higher rates of clinically significant invasive secondary infections and associated poor outcomes. Given there is limited information suggesting improved outcomes with these prolonged courses, risk to benefit analysis must be considered when deciding whether to extend corticosteroid treatment for more than 10 days for COVID-19.

Disclosures
All Authors: No reported disclosures.
297. Secondary Bacterial Blood Stream Infections in Patients Hospitalized with COVID-19
Authors: Adnan Fareeha , Khan Mariam A , Umer Amna , Khursheed Nazia 
Published: December 2022

Abstract

Background
Nosocomial Bloodstream infection (nBSI) in COVID 19 patients is an emerging clinical concern for physicians. In this study, we aimed to assess the prevalence of BSI in COVID-19 patients admitted to our hospital, The Indus Hospital, Karachi, Pakistan.

Methods
This retrospective study included the RT-PCR confirmed COVID-19 patients admitted to our hospital from March 2020 to December 2021. Demographics, the incidence of BSI, frequency of pathogens from the positive blood cultures, antibiotics resistance pattern, and frequency of Multidrug-Resistant Organisms (MDROs) were obtained from the hospital’s electronic medical record. Blood cultures were performed using BD BACTEC. Bacterial identification was done by using Analytical Profile Index(API) whereas antimicrobial susceptibility testing of isolates was performed by the Kirby-Baur disk diffusion method and VITEK® 2 COMPACT.

Results
Our data showed that 25% of the patients admitted to our hospital developed BSI. The incidence of BSI was higher in males than in females (62.6% vs 37.4%) and most of the patients were in the age group of 46-60 years (n=93). Gram-negative pathogens were pre-dominantly identified, (50.67%), followed by yeast (12.9%), and Gram-positive pathogens (11.8%). Among these isolates, Acinetobacter sp. was the most commonly identified pathogen. Figure 1 shows the incidence of BSI and Figure 2 shows the distribution of all the pathogens identified from the positive blood cultures. Antibiotics resistance pattern showed a higher prevalence of MDROs. Among the MDROs, Acinetobacter sp. was highest in number (97.6%), followed by 66.6% of Pseudomonas, 63% of E.coli, 62% of S. aureus, 61.5% of Enterococcus, and 50% of Klebsiella sp.

Conclusion
Our findings indicated the incidence of BSI in 25% of COVID-19 in-patients. There is a significant prevalence of MDROs among which compelling prevalence of Acinetobacter sp. was observed. The COVID-19 pandemic overburdened the already vulnerable health care systems and made it difficult to adhere to infection control practices leading to the emergence of MDROs. Moreover, timely initiation of empirical antibiotics could also reduce the incidence of BSI in patients. Lastly, further multi-centered studies are needed for the evaluation of the incidence of BSI in our region.

Disclosures
All Authors: No reported disclosures.
308. Do lung ultrasound abnormalities change during hospitalization for COVID-19?
Authors: Hwang Jimin , Blair Paul W , Siddarthan Trishul , Liu Gigi , Cui Erjia , Bai Jiawei , East Joshua , Herrara Phabiola , Fong Tiffany , Mahadevan Varun , Hossen Shakir , Seo Stefanie , Sonuga Olamide , Lawrence Joshua , Anova Lalaine , Fenstermacher Katherine , Shea Sophia , Rothman Richard E , Hansoti Bhakti , Sauer Laruen , Crainiceanu Ciprian , Clark Danielle , Clark Danielle , Clark Danielle 
Published: December 2022

Abstract

Background
While point-of-care ultrasound (POCUS) has been used to track disease resolution, temporal trends in lung ultrasound (LUS) findings among hospitalized patients with COVID-19 is not well-characterized.

Methods
We studied 413 LUS scans in 244 participants ≥ 18 years of age hospitalized for COVID-19 pneumonia within 28 days of symptom onset from April, 2020 until September, 2021 at the Johns Hopkins Hospital, Baltimore Maryland. All patients were scanned using a 12-lung zone protocol and repeat scans were obtained in 3 days (N=114), 7 days (N=53), and weekly (N=9) from the initial scan. Participants were followed to determine clinical outcomes until hospital discharge and vital status at 28-days. Ultrasounds were independently reviewed for lung artifacts, and the composite mean LUS score (ranging from 0 to 3) across lung zones was determined. Trends of mean LUS scores and % lung fields with A-lines (indicating proportion of normal lung fields) were plotted by peak severity (mild, moderate, and severe defined by the World Health Organization Ordinal Scale) over time from symptom onset. Differences in mean LUS score or % A-lines changes over time between peak severity levels were evaluated using a Kruskal-Wallis test and linear mixed-effected models with an exchangeable correlation structure.

Results
Among 244 patients in our cohort (mean age of 58.2 (SD 15.0) years, and 55.7% female) (Table 1), there was no change in average mean LUS scores between the first two visits by severity groups (Figure 1; Kruskal-Wallis p=0.63). Mean LUS scores were elevated by 0.22 (p&lt; 0.001) in a dose-response manner regardless of duration of illness, but there was no change over time associated with peak severity (p=0.73). Similarly, percentage of A-lines were in 13.9% less lung fields for each increase in peak severity (p&lt; 0.001; Figure 2) regardless of duration of illness. However, a change in mean LUS score did not differ significantly among peak severity levels (p=0.36).

Conclusion
Mean LUS scores correlated with clinical severity among hospitalized adults when assessed cross-sectionally, however mean LUS score did not change or differ between peak severity levels over the time course of hospitalization. These results do not support serial LUS scans to monitor disease progression.

Disclosures
All Authors: No reported disclosures.
313. Performance of Rapid Diagnostic Testing at Days 4-6 from Diagnosis: Implications for Discharge from Isolation on a University Campus
Authors: Atarere Joseph , Zhou Zhenwei , Turcinovic Jacquelyn , Seitz Scott , Sher-Jan Cole , Gilbert Madison , White Laura F , Hossain Mohammad , Overbeck Victoria , Mistry Roxanne M , Doucette-Stamm Lynn , Platt Judy T , Nichols Hannah E , Hamer Davidson H , Klapperich Catherine M , Jacobson Karen R , Connor John , Bouton Tara C 
Published: December 2022

Abstract

Background
Omicron rapidly replaced delta as the predominant strain causing COVID-19 related illness in the United States (US) in December 2021, the same month the US CDC reduced the recommended isolation period from 10 to 5 days for asymptomatic individuals or those with resolving symptoms. New evidence suggests some asymptomatic individuals with omicron remain culture positive beyond 5 days from diagnosis. We sought to evaluate the performance of a SARS-CoV-2 antigen rapid diagnostic test (RDT) in predicting persistent potential for transmission at the end of a five-day isolation period among young, fully vaccinated individuals in a university community setting.

Methods
A subgroup of participants enrolled in a longitudinal COVID-19 cohort were asked to self-perform RDTs on days 4 to 6 from diagnostic test date in addition to a separate self-collected anterior nasal swab used for culture and RT-PCR, and a daily symptom screen (15 COVID-19 symptom questions on a 4-point scale). We calculated the daily and overall sensitivity and specificity of the RDTs in comparison to SARS-CoV-2 culture result. We also compared the N1 cycle threshold (CT) values and symptom score on each day of the study by RDT results.

Results
Of 23 participants, the mean age was 20 years, all had completed their primary COVID-19 vaccine series, and 13 (65.0%) had received a booster vaccine (Table 1). Compared to culture, sensitivity and specificity of the RDTs were 100% and 62% respectively (Table 2). Compared to participants with negative RDTs, median CT values were lower in those with positive RDTs on each day of the study (Figure 1). Participants who had positive RDTs on all three days had higher symptom scores (Figure 2) than those without.

Conclusion
RDTs have a high sensitivity in detecting culture positive SARS-CoV-2 on Days 4 to 6 from initial diagnostic test. However, the high false positive rate of 38% means that over a third of culture negative individuals will stay in isolation longer than necessary if RDTs are used in test to release from isolation protocols. Viral loads (CT values) and symptom scores were higher for participants with persistently positive RDT result. An approach that uses a combination of RDTs, CT values and symptom score may prove useful in guiding isolation duration.

Disclosures
Davidson H. Hamer, MD, Trinity Biotech: Advisor/Consultant Catherine M. Klapperich, Ph.D., BioSens8, LLC: Ownership Interest.
325. Molecular Characterization of Antimicrobial Resistance Genes in Neisseria gonorrhoeae in Southeast Michigan
Authors: Shallal Anita , Suleyman Geehan , Gurdziel Katherine , Perri Mary , Zervos Marcus , Tibbetts Robert 
Published: December 2022

Abstract

Background
Antimicrobial resistance (AMR) in Neisseria gonorrhoeae (NG) is a public health crisis. Diagnosis of infection is primarily established using nucleic acid amplification technologies (NAATs) without susceptibility testing; thus rapid identification of resistance determinants is crucial. Whole-genome sequencing (WGS) is a promising alternative to current susceptibility methods. The purpose of this study was to describe AMR genes in a subset of isolates using WGS from Southeast Michigan.

Methods
Isolates, demographic data, and minimum inhibitory concentrations (MIC) via E-test (ceftriaxone/CRO) and broth microdilution (azithromycin/AZM) were obtained from the Michigan Department of Health and Human Services. Libraries from isolates were generated using QIAseq FX DNA library kit before sequencing on NovaSeq 6000. Reads were trimmed [Trimmomatic] and aligned to the NG genome [Burroughs-Wheeler Aligner] before processing with Samtools suite for variant detection and consensus WGS determination. AMRFinderPlus was used to categorize AMR genes and resistance-associated point mutations.

Results
Total of 38 isolates were analyzed. The majority were from males (63%) and Blacks (44.7%) living in Detroit City proper (47.3%) with median age 25 (range 13-56), unknown HIV status (55.2%) and sexual orientation (47.3%) (Table 1). Urine (47.3%) was the most common specimen source, followed by cervix/vagina (28.9%). More than a third had prior NG and other sexually transmitted infections. Eight resistance genes were found among the 38 isolates (Figure 1). The penA gene associated with cephalosporin resistance was found in all isolates; however, all isolates were susceptible to CRO (CLSI susceptible breakpoint MIC &lt; 0.25). The mtrR gene associated with macrolide resistance was noted in 86.8% isolates. Among 33 isolates where AZM susceptibility was available, resistance was noted in 9 (27%) (CLSI resistance breakpoint MIC &gt; 1).

Conclusion
We describe a potential utility for WGS to identify AMR genes in NG. Although numerous β-lactam resistance genes were detected in all isolates, all remained susceptible to CRO. Further research is needed to determine the extent to which genetic diversity affects phenotypic susceptibilities in NG.

Disclosures
All Authors: No reported disclosures.
337. Diagnostic Yield and Impact on Antimicrobial Management of 16s rRNA Testing on Clinical Specimens
Authors: Eamsakulrat Pruke , Phuphuakrat Angsana , Santanirand Pitak 
Published: December 2022

Abstract

Background
16s rRNA gene sequencing has an advantage over traditional bacterial culture in situations where bacteria are difficult to culture, unculturable, or have previously been exposed to antimicrobial. The study on its applicability to direct clinical specimens is still limited. We studied the value of 16s rRNA gene sequencing from direct clinical specimens on antimicrobial management.

Methods
Inpatient adults whose attending physician requested 16s rRNA gene sequencing and corresponding bacterial culture from a direct clinical specimen were prospectively included between January and December 2021. Diagnostic yield and the impact of 16s rRNA gene sequencing on antimicrobial management were investigated.

Results
A total of 434 specimens from 374 patients were requested. All patients had a complete follow-up and had a definitive final diagnosis. The sensitivity and specificity of 16s rRNA gene sequencing were 38.3% and 93.9%, respectively. The agreement between 16s rRNA gene sequencing and conventional culture among specimens obtained from bacterial infection cases was 83.8% (the κ coefficient 0.664, p&lt; 0.001). Among bacterial infection cases, the proportion of 16s rRNA gene sequencing positive/culture-positive was 32.4% (82 specimens), and the proportion of sequencing positive/culture-negative was 5.9% (15 specimens). The impact on antimicrobial management occurred in 10 (2.3%) specimens, which all resulted in the continuation of antibiotics. An impact on antimicrobial management was highest in the skin and soft tissue infection, followed by bone and joint infection. In contrast, CAP/HAP/VAP was less likely to benefit from this test. Long turnaround time was the limitation of the test in this study, the median (interquartile range) was 11 (9-13) days in the 16s rRNA gene sequencing positive group, and 2 (1-4) days in the 16s rRNA gene sequencing negative group.

Conclusion
The overall diagnostic yield of 16s rRNA gene sequencing in bacterial infection cases was fair. 16s rRNA gene sequencing was useful in selected cases, but it cannot replace traditional culture. The negative result did not exclude bacterial infection. Restrictions on test requests may improve test utilization in this setting.

Disclosures
All Authors: No reported disclosures.
340. GeneXpert Ultra for Diagnosis of Central Nervous System Tuberculosis in the High Tuberculosis Prevalence Country - A Prospective Study from India
Authors: Naguthevar Santhanam , Kumar Deepak , Sharma Shivang , ID D M , Bohra Gopal Krishna , Meena Durga Shankar , Midha Naresh Kumar , Kombade Sarika P , Jain Vidhi , Garg M K , Singh Kuldeep 
Published: December 2022

Abstract

Background
Early diagnosis and initiation of antitubercular treatment are vital steps to reducing the impact of TB in high burden countries. The molecular method like GeneXpert has significantly improved the diagnosis of TB. GeneXpert Ultra is more sensitive to the diagnosis and helps in paucibacillary samples like cerebrospinal fluid (CSF). This study aims to provide its utility in diagnosis of central nervous system tuberculosis (CNS TB) in high TB burden geography.

Methods
This prospective observational study included the suspected cases of CNS TB with age ≥12 years. Patients who presented with ≥ 5 days history of CNS symptoms suggestive of tuberculosis with a lancet score of ≥ 6 on combination of clinical, CSF and imaging criteria were included in the study. Patients diagnosed with aetiology other than tuberculosis for CNS disease were excluded. CSF was analysed for GeneXpert Ultra and mycobacterial culture. The sensitivity, specificity, positive predictive value (PPV), and Negative predictive value (NPV) of GeneXpert Ultra were analysed in comparison with culture results.

Results
A total of 107 patients with mean age of 33.2±18.5 years were analysed. CSF mycobacterial culture was positive in 45.8% (n=49) of patients. However, Mycobacterial tuberculosis via GeneXpert Ultra was detected in 57.9% (n=62) of patients. Sensitivity, specificity, PPV and NPV for GeneXpert Ultra were found 83.7%, 63.8%, 20.4% and 97.2% respectively. According to the lancet score, 70.1% (n=75) and 29.9% (n=32) of patients had probable and possible CNS TB, respectively. Among them, definitive CNS TB were diagnosed in 65.3% (n=49) and 65.6% (n=21) patients with probable and possible CNS TB, respectively.

Conclusion
GeneXpert Ultra has an excellent sensitivity and negative predictive value for the diagnosis of CNS TB in CSF samples. Even with possible CNS TB according to the lancet score, it is better to consider antitubercular treatment in a high TB burden country.

Disclosures
All Authors: No reported disclosures.
344. VersaTrek versus Virtuo Blood Culture System’s Effect on Diagnostic Test Utilization and Patient Outcomes, a Quasi-Experimental Study
Authors: Dillon William P , Khan Naoshin , Nachawati Dana , Alangaden George J , Samuel Linoj , Ramesh Mayur 
Published: December 2022

Abstract

Background
Prior studies evaluating the sensitivity blood cultures utilizing the Virtuo blood culture system versus the VersaTREK blood culture system have suggested increased sensitivity with the Virtuo system. Studies evaluating if this increased sensitivity effects patient outcomes are lacking. This study evaluates the effect of replacing the VersaTREK system with the Virtuo system on morbidity and mortality in patients with Staphylococcus aureus bacteremia.

Methods
This quasi-experimental study was performed at Henry Ford Health System in Southeast Michigan. We analyzed all patients with positive blood cultures for Staphylococcus aureus between 3/1/18 and 9/30/18 (VersaTREK system) and 3/1/19 and 9/30/19 (Virtuo system). The VersaTREK arm had 267 patients and the Virtuo arm 404. Patients transferred to or from outside facilities with ongoing bacteremia were excluded. Primary outcomes were differences in length of stay, mortality at 14, 30, and 90 days from completion of therapy, and hospitalization for recurrence of bacteremia within 30 days. Secondary outcomes were differences in length of therapy, rates of diagnostic imaging tests to assess for persistent foci of infection or an unknown source of persistent bacteremia, and length of bacteremia. Data were analyzed using SPSS for Macintosh using Pearson’s chi-square test and Student’s t-test. A p &lt; 0.05 was considered statistically significant.

Results
Demographics of the study populations were equal however, the Charlson Comorbidity Index for VersaTREK arm compared to Virtuo (3.5 to 3.1) trended toward significance (p=0.05) (Table 1). There was no difference in length of bacteremia, lengths of antibiotic therapy, CT scans, or echocardiograms performed. More MRIs were performed in the Virtuo arm (p=&lt; 0.001) (Table 2). There was no difference in recurrence of bacteremia, patient death due to bacteremia, length of hospital stay, or 30 day readmission for recurrence of bacteremia (Table 3).

Conclusion
This is the first study to evaluate how increased sensitivity of a blood culture system effects patient outcomes. Our results suggest that Staphylococcus aureus bacteremia may be over treated in blood cultures systems that are highly sensitive. Further prospective studies are needed to explore this further.

Disclosures
All Authors: No reported disclosures.
348. Cell-free plasma next-generation sequencing assists in the evaluation of invasive mold infection in patients with COVID-19: a case series
Authors: David Joshua , Kolipakkam Bharadhwaj , Morales Megan M , Vissichelli Nicole C 
Published: December 2022

Abstract

Background
Distinguishing COVID-19 Associated Pulmonary Aspergillosis (CAPA) and invasive mold infections (IMIs) from other causes of secondary pneumonia in COVID-19 can be challenging. 1,3-β-D-Glucan and galactomannan are commonly utilized biomarkers for the workup of IMIs but are limited by a lack of specificity and sensitivity respectively. Cell-free plasma next-generation sequencing (cfNGS) is a promising non-invasive approach that can provide direct detection of pathogens in patient's serum. This study explored its potential role in the evaluation of secondary pneumonia in patients with COVID-19.

Methods
We performed a retrospective single-center observational study from March 2020 to December 2021 at Virginia Commonwealth University Medical Center, a 811-bed tertiary care center, to evaluate patients with laboratory confirmed SARS-CoV-2 virus infection who underwent cfNGS for the evaluation of CAPA. CfNGS (Karius, Inc., Redwood City, CA) was performed at the discretion of the clinical provider and we evaluated the test indication, patient history, clinical impact, correlation with serum biomarkers, and 30 day all-cause mortality.

Results
Thirteen patients were evaluated and none had Aspergillus species detected. One patient had Pneumocystis jirovecii on cfNGS. There was a 76.9% (10/13) concordance rate with patients’ serum fungal biomarkers. CfNGS also detected concomitant organisms in 53.8% (7/13) of our cohort. These data assisted in changes of clinical management for 84.6% (11/13) of patients and lead to the change in antifungal usage in 69.2% (9/13).

Conclusion
In this study, both negative and positive cfNGS test results assisted in important clinical decision making. cfNGS may have a role in the evaluation of CAPA or other IMIs in patients with COVID-19.

Disclosures
Megan M. Morales, MD, Karius: Paid speaker.