bluuebunny/crossref_metadata_2025 huggingface dataset:
515. The Impact of Prolonged Steroid Use on Critically Ill COVID-19 Patients: A Retrospective Cohort Study
Authors: Han Jaijun , Bae Seongman , Jung Jiwon , Kim Min Jae , Chong Yong Pil , Choi Sang-Ho , Lee Sang-Oh , Kim Yang Soo , Chang Eui Jin , Kim Sung-Han
Published: November 2023

Background

Dexamethasone was found to decrease mortality in COVID-19 patients needing oxygen support. However, there is no clear guidance on the duration of steroid use after 10 days. This study aims to compare clinical outcomes of critical COVID-19 between patients abruptly discontinuing steroids within 10 days and those tapering off beyond 10 days.

Methods

This retrospective cohort study included adult COVID-19 patients with a severity score of 6-9 on the World Health Organization-Clinical Progression Scale (WHO-CPS). Patients were divided into two groups based on the duration of maintaining steroids and compared for clinical outcomes such as incidences of rebound pneumonia and infectious complications, 28-day and in-hospital mortality, and readmission or revisit to the emergency room within three months after discharge. The study used a one-to-one propensity score matching analysis to eliminate potential confounding factors.

Results

There were 121 patients who received dexamethasone for up to ten days and discontinue it abruptly and 139 patients who tapered off steroids after taking dexamethasone for up to ten days. After propensity score matching, 58 patients were included in each group and there was no significant difference in baseline characteristics between both groups. Duration of hospitalization was significantly longer in the steroid-tapering group (median 20.0 days, 95% confidence interval (CI) 13.0-29.0 days) than the group with abrupt discontinuation of dexamethasone (13.0, 95% CI 10.0-17.0) (p< 0.001). Also, there were six cases of rebound pneumonia in each group and 28-day mortality was 10.3% in both groups. Analyses after propensity score matching showed that there was no significant difference in 28-day and in-hospital mortality, the incidence of rebound pneumonia, infectious complications, and readmission or revisit to the emergency room between both groups.

Clinical characteristics of the study patients before and after propensity score matching

Clinical outcomes for the study patients before and after propensity score matching

Survival analysis of 28-day mortality according to steroid tapering in critical COVID-19 patients

Conclusion

Tapering and prolonged use of steroids after administering dexamethasone for up to ten days did not significantly improve the 28-day and in-hospital mortality, the incidence of rebound pneumonia, and readmission or revisit to the emergency room in critical COVID-19 patients with a severity score of 6-9 on the WHO-CPS.

Survival analysis of in-hospital mortality according to steroid tapering in critical COVID-19 patients

Disclosures

All Authors: No reported disclosures
518. Comparable Outcomes of Remdesivir and Sotrovimab among High-risk Patients with Mild to Moderate COVID-19 During the Omicron BA.1 Surge
Authors: Chesdachai Supavit , Rivera (O'Connor) Christina G , Mara Kristin , Teaford Hiliary R , Suarez Maria Gonzalez , Larsen Jennifer J , Ganesh Ravindra , Tulledge-Scheitel Sidna , Razonable Raymund R
Published: November 2023

Background

Two independent placebo-controlled clinical trials conducted prior to SARS-CoV-2 Omicron demonstrated that sotrovimab and remdesivir reduced hospitalization among high-risk outpatients with mild to moderate COVID-19. However, their effectiveness have not been directly compared.

Methods

This retrospective study examined all high-risk outpatients with mild to moderate COVID-19 who received either remdesivir or sotrovimab at Mayo Clinic during the Omicron BA.1 surge from January to March 2022. COVID-19-related hospitalization or death within 28 days were compared between the two treatment groups.

Results

Among 3,257 patients, 2,158 received sotrovimab and 1,099 received remdesivir. Patients treated with sotrovimab were younger (median age, 60 vs. 69 years) and had lower comorbidity (Monoclonal Antibody Screening Score, 5 vs. 6; Charlson Comorbidity Index, 3 vs. 4), but were more likely to be immunocompromised (47.3% vs. 30.2%) than remdesivir-treated patients. The majority (89%) had received at least one dose of COVID-19 vaccine (median, 3 doses [IQR 2-3] for both groups). COVID-19-related hospitalization (1.5% and 1.0% in remdesivir and sotrovimab groups, respectively, p=.15) and mortality within 28 days (0.4% in both groups, p=.82) were similarly low. A propensity score weighted analysis demonstrated no significant difference in the rates of COVID-related hospitalization and death within 28 days between the two groups.

Conclusion

This study demonstrated favorable outcomes that were not significantly different between patients treated with remdesivir or sotrovimab. As sotrovimab is no longer authorized, these results support the continued use of remdesivir for treating high-risk patients with COVID-19 during the current Omicron-predominant epoch.

Disclosures

Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Maria Gonzalez Suarez, M.D., Ph.D., Gilead: Grant/Research Support Ravindra Ganesh, M.B.B.S., M.D., Alpaca Health: Advisor/Consultant Raymund R. Razonable, MD, Allovir: Endpoint Adjudication Committee|American Society of Transplantation: Board Member|Gilead: Grant/Research Support|Novartis: DSMB|Regeneron: Grant/Research Support|Roche: Grant/Research Support
533. Use of Different Communication Types for Telehealth for COVID-19 During Implementation of a State Telehealth Test to Treat Program in Minnesota
Authors: Lim Sarah , Dubelko Paige , James Walter , McLachlan Erin , Tsay David , Lynfield Ruth
Published: November 2023

Background

Telehealth programs for COVID-19 have expanded and may use multiple types of communication, such as mobile apps, web-based or telephone. Data on use of these communications are lacking, particularly in different age groups. We assessed use of three different communication types during implementation of a test to treat program for COVID-19 in Minnesota.

Methods

Minnesota launched its telehealth program in two phases: Phase 1 (mobile app only) during initial rollout from 12/15/22 – 1/5/23 and Phase 2 (addition of web and phone options) from 1/6/23 – 4/30/23. Data on users of the program were provided by the vendor (Cue Health), including communication type (app, web, phone), number of attempts, antiviral prescription, age, and sex.

Results

Data were available for 2093 patients who completed the intake process between 12/15/22 and 4/30/23, of whom 1928 (92%) completed the consultation process and 1808 (86%) received an antiviral. 60% of users were female. 250 patients (12%) completed the intake more than once on the same day, which may reflect multiple attempts due to technical barriers. During the study period, patients aged 35-44 and ≥ 65 years made up the largest proportion of users by age group (each had 464 patients, each 22% of total, Figure 1). 37% of users accessed the program via the phone and 37% via the app, with 26% using the website. Communication preferences varied by age, with increased use of the phone option in older age groups (54% of ≥ 65 vs 30% of 18-34 years, Figure 2). In comparison to users who made a single attempt, users who made multiple attempts were more likely to be younger (48 vs 51 years, p=0.02), and less likely to be prescribed an antiviral (80% vs 91%, p< .001). Users with multiple attempts were more likely to have used the web option for their first attempt (47% vs 24%, p< .001). Those with multiple attempts generally used the same communication type for all attempts (204/250); of those who switched, the commonest switch was to the phone (39/46).

Conclusion

Of the three communication types, the phone and app options were most popular, with a trend towards more phone use in older age groups. A phone option should be considered in future telehealth initiatives, including as a backup for those with technical barriers to app or web-based communication.

Disclosures

David Tsay, MD PhD, Cue Health: Chief Medical Officer|Cue Health: Stocks/Bonds
535. Risk Factors for Seeking Medical Care Following Monoclonal Antibody Treatment For COVID-19
Authors: MALIK I S M A I L O , Szpunar Susan M , Salaytah Natali , Bhargava Ashish , Sharma Mamta
Published: November 2023

Background

The FDA issued emergency use authorization for neutralizing monoclonal antibodies (mAb) for the treatment of mild-moderate coronavirus disease 2019 (COVID-19) in patients who were at high risk of disease progression.

Methods

In this case-control study, we assessed risk factors for patients with mild-moderate COVID-19 infection treated with mAb on the composite outcome of subsequent evaluation in the Emergency Department (ED) or inpatient admission through December 1, 2020, through May 30, 2022. Cases were patients who failed MAB and visited the ED or were hospitalized within four weeks of their MAB treatment; controls received MAB but did not visit the ED or were not hospitalized within four weeks of MAB treatment. Cases were matched to controls in 1:1 ratio for the patient age ± 5 years. and for the calendar month of positive COVID tests. Data were analyzed using Student’s t-test, the chi-squared test, the Mann-Whitney U test and logistic regression using SPSS v. 29.0. The study was approved by the Ascension IRB.

Results

Of 212 patients who received mAb treatment, the mean (SD) age was 61.3 (±18) years; 51.8 % (99) were female, and 84.8% (162) white. The mean body mass index of the cohort was 32.6 ± 8.5 kg/m2. Following mAb infusion, 106 cases had a positive composite outcome of interest. Patients with peptic ulcer disease (PUD) (64.4% vs 35.6%; p=0.029), asthma (72.7% vs 27.3%; p=0.024), and chronic lung diseases (12.5% vs 35.5%; p=0.001) were more likely to seek medical care in the ED or hospital post mAb infusion. Alcohol users were less likely to seek medical care following mAb infusion (41.7% vs 58.3%; p=0.013). The number of reported days of symptoms prior to mAb infusion were 5.81 days in cases versus 5.79 days in controls (p=0.98). There were no differences in sex, BMI, tobacco use or vaccinations rates between the two groups. In multivariable logistic regression, factors associated with seeking medical care post mAb infusion were Black race (OR 3.1; 95% CI 1.1-9.2), peptic ulcer disease (OR 3.3; 95% CI 1.1-9.7) and alcohol use at the time of mAb treatments (OR 0.5; 95% CI 0.3-0.97)

Conclusion

Independent risk factors for seeking medical care following mAb treatment for COVID-19 were Black race and peptic ulcer disease while alcohol users were less likely to seek medical care following the mAb infusion.

Disclosures

All Authors: No reported disclosures
541. The Effect of Early Remdesivir Administration in COVID-19 Disease Progression
Authors: Platzer Moritz , Totschnig David , Wenisch Christoph , Zoufaly Alexander
Published: November 2023

Background

Since the global outbreak of SARS-CoV-2, antiviral drugs have played a major role in the treatment of COVID-19 by reducing complications and mortality. Remdesivir is an effective therapeutic option for hospitalized patients with risk for clinical progression with COVID-19 who cannot receive nirmatrelvir/ritonavir mainly because of kidney & liver disease or issues with drug- interactions. Remdesivir can be administered for as long as 7 days after symptom onset according to treatment recommendations, but antiviral treatment work best when given as early as possible. In this study we investigated the impact of timing of remdesivir administration on clinical outcome.

Methods

Retrospective clinical data from consecutive PCR-confirmed SARS-CoV-2 patients who received remdesivir and were hospitalized at the department of infectious diseases, Clinic Favoriten (Vienna) from the 1st of July 2021 until the 31st of April 2022 were analyzed. We divided patients into two groups of early (0-3 days since symptom onset) and late (≥ 4) remdesivir administration. The primary outcome was in hospital disease progression measured according to the WHO COVID-19 Clinical Progression Scale (≥1 point). In a multivariable logistic regression adjusted for age, sex, SARS-CoV2 variant, and COVID-19 vaccination status, clinical outcomes were assessed.

Results

219 patients who received remdesivir could be included in the analysis. The ratio between early and late group was 67.6% to 32.4%. After adjusting for age, sex, vaccination status, and viral variant, patients who received remdesivir more than 4 days after symptom onset tended to have a higher probability of clinical deterioration (OR 2,13 95% CI 0,98 to 4,64, p= 0,056) including a higher probability for high-flow oxygen therapy (OR 2,52 95% CI 1,40 to 4,52, p= 0,002) or being admitted to ICU (OR 4,34 95% CI 1,38 to 13,67, p= 0,012). There was no significant difference in mortality.Table 1.Demographic and Clinical Characteristics of the PatientsTable 2.Clinical outcomes adjusted to age, sex, virus variant and vaccination status

Conclusion

Our data show that the risk for complications of COVID19 including a need for high-flow oxygen therapy and ICU admission is elevated when remdesivir is administered after day 4 in hospitalized patients. This may indicate that patients at increased risk for severe disease who cannot take oral options should receive antiviral therapy with remdesivir as early as possible.

Disclosures

Moritz Platzer, MD, Gilead: Grant/Research Support
542. Evaluation of Remdesivir to the Outcomes of Hospitalized Patients with COVID-19 Infection in a Tertiary Care Hospital in Southern India
Authors: Raju Jomel , Tom Maria
Published: November 2023

Background

Remdesivir was the only antiviral used in the treatment of COVID-19 in the first wave of the COVID-19 pandemic, following the adaptive COVID-19 treatment trial-1 interim analysis report. However, its use in moderate to critical hospitalized COVID-19 patients continues to be controversial. Therefore, through this nested case-control study in a cohort of hospitalized COVID-19 patients, we aimed to evaluate the benefit of RDV in the treatment of moderate to severe COVID-19.

Methods

In a cohort of 1,531 moderate to critical COVID-19 patients, we retrospectively performed a nested case-control study where 515 patients on Remdesivir were compared to 411 patients with no Remdesivir. Cases and controls were matched for age, sex, and severity. The primary outcome was in-hospital mortality and secondary outcomes were duration of hospital stay, need for intensive care unit (ICU), progression to oxygen therapy, progression to non-invasive ventilation, progression to mechanical ventilation, and duration of ventilation.

Results

The mean age of the cohort was 57.05 + 13.5 years. 75.92% were males. Overall, in-hospital mortality was 22.46% (n = 208). There was no statistically significant difference in all-cause mortality among cases and controls (20.78% vs. 24.57%, p = 0.17). Progression to noninvasive ventilation was lower in the Remdesivir group (13.6% vs 23.7%, p < 0.001), however, progression to mechanical ventilation was higher in the Remdesivir group (11.3% vs 2.7%, p-value < 0.001*). In a subgroup analysis of critically ill patients, the use of Remdesivir lowered mortality (OR 0.32 95% CI: 0.13 - 0.75).

Conclusion

Remdesivir did not decrease the in-hospital mortality in moderate to severe COVID-19 but decreased progression to non-invasive ventilation. Its mortality benefit in critically ill patients needs further evaluation. Remdesivir may be useful if given early in the treatment of patients with moderate COVID-19.

Disclosures

All Authors: No reported disclosures
554. Association of emr and mdt Genes in Carbapenem Resistant Acinetobacter baumannii with Clinical Outcome in A Tertiary Care Hospital
Authors: CHAUDHARY M O N I K A , Kumar Deepak , Bohra Gopal Krishana , Midha Naresh Kumar , Meena Durga Shankar , Tak Vibhor , Garg M K , Mohammed Sadik , Rohilla Amit Kumar
Published: November 2023

Background

Carbapenem Resistant Acinetobacter baumannii (CRAB) is one of the most common cause of nosocomial infections in ICUs and associated with high mortality. Because the organism can acquire resistance to multiple drugs by various mechanisms, very few treatment options have been left. We evaluated the genes which conferred multidrug resistance to clinically virulent CRAB isolated from 4 critically ill patients and correlated them with their clinical outcome.

Methods

It was a small prospective study under the Antimicrobial Stewardship Program in a tertiary care hospital of Western Rajasthan, India. It included 4 critically ill patients who were diagnosed with hospital acquired CRAB bactaeremia in the month of October and November 2022. They were admitted in ICU and were on ventilator > 48 hours post admission with no comorbidities. Microbiologically proven CRAB isolated from the blood of these 4 patients were sent for Whole Genome Sequencing(WGS).These samples were sequenced using Novaseq with a read length of 151 bp. 2 different strains of Acinetobacter baumannii were identified in these 4 samples- XH731 and WKA02. Denovo assembled fasta sequence was annotated using Prokka to predict CDS, genes and other features of genome.

Results

Table1 is showing the presence of emr and mdt genes in the CRAB strains isolated from the blood of 4 patients. They are responsible for colistin resistance and multidrug resistance by formation of efflux pumps respectively. CRAB isolated from patient C was having emrA1, emrA2, emrA3, emrA4, emrA5, mdtE, mdtK, mdtA1, mdtA2, mdtA3, mdtA4, mdtC. This patient succumbed to death within 5 days of admission despite of appropriate combination therapy, implying very high virulence of CRAB harboring these genes. Moreover, in patient D extra number of drug resistant genes were found as compared to patient A and B.

Multidrug resistant genes found in CRAB isolated from 4 patients of AICU and their outcome

Conclusion

Increased virulence of CRAB due to its resistance to almost every drug has made its management very difficult. WGS can be used to identify certain genes which may be responsible for rapid progression of disease. Presence of emrA4, emrA5, mdtK, mdtA3 and mdtA4 genes responsible for formation of efflux proteins may be associated with increased mortality as observed in our study.

Disclosures

All Authors: No reported disclosures
555. Clinical impact and real-life utilization of Karius testing: a retrospective analysis of cases from an urban, academic medical center
Authors: Conway-Pearson Liam , Orner Erika , Thwe Phyu , Szymczak Wendy , McCort Margaret E
Published: November 2023

Background

Metagenomic next-generation sequencing (NGS) of microbial cell-free DNA is a relatively novel diagnostic technique that may potentially expedite and/or supplement pathogen-specific infectious disease diagnoses, minimize the time to appropriate antibiotic therapy, and reduce unnecessary and invasive testing. However, careful diagnostic stewardship is necessary to ensure that such tests are being ordered in the appropriate patient population.

Methods

A retrospective chart review of all patients for whom the Karius NGS test was sent at our institution between Jun 13, 2020-Jul 22, 2022 was performed. Clinically relevant pathogens were defined as diagnoses that led to change in antimicrobial therapy. Stata statistical software (version 17.0, College Station TX) was used to analyze patient and hospitalization risk factors associated with Karius testing.

Results

Thirty cases among 29 unique patients for whom Karius testing was performed were included in our review. Patient characteristics are shown in Table 1. Twenty-one patients (72%) were immunocompromised, including 14 (47%) with solid organ transplant (SOT) and 9 (30%) with malignancy. Mean hospital length of stay (LOS) prior to Karius test collection was 15.8 days (+/- 21.6 days, range 1-120). Reasons for sending Karius are shown in Fig 1. Three patients (10%) had tissue-specific NGS testing performed in addition to Karius. On average, patients received 13.9 days of antibiotics prior to Karius (+/-10.11, range 0-37). Mean turnaround time for Karius results was 38.3 hours (+/- 16.5, range 23-79). Ten (34.5%) Karius results identified no pathogens. Karius identified fungal organisms in 3 (10%) tests, one of which correlated with true infection. Karius results correlated with other infectious diagnostics (such as viral PCR or cultures) in 10 (33%) cases. Clinically relevant pathogens (not identified by other testing) were identified by Karius in only 3 (10%) cases. There was no statistically significant correlation between pathogen detection by Karius and history of HIV (p=0.27), transplant (p=0.70), malignancy (p= 0.21), or number of days from admission to test (p=0.66)

Table 1

Patient characteristics (N=29 unique patients, 30 tests)

Figure 1

Reasons for Karius test

Conclusion

Metagenomic NGS is an exciting area of diagnostic innovation, but more studies are needed to determine when and where this test is best utilized.

Disclosures

All Authors: No reported disclosures
556. Commercial Microbial Cell-Free DNA Next-Generation Sequencing in a Pediatric Quaternary Care Facility Yields Limited Diagnostic Utility
Authors: Osborn Lucas J , Kamel Dina , Malhotra Sanchi , Posch Leila C , Costales Cristina , Bard Jennifer Dien
Published: November 2023

Background

Microbial cell-free DNA next-generation sequencing (mcfNGS) is a novel diagnostic tool increasingly utilized as a rapid, noninvasive approach to aid in the diagnosis of infectious diseases. However, its utility in pediatric patients is not well established. This study aimed to explore the diagnostic utility of commercial microbial cell-free DNA sequencing in a pediatric quaternary care facility.

Methods

This retrospective study included 15 patients with mcfNGS results between June 2018 and April 2023. Chart abstraction was performed to determine changes in clinical management. Change in management was defined as any clinical decision implemented based on mcfNGS results. Overall clinical impact was defined as either a beneficial or deleterious change in patient outcome resulting from clinical management changes made based on mcfNGS results.

Results

Of the 15 patients, a total of 14 valid results were reported, 13 (86.7%) of which were from the first attempt. At least one microbial target was detected in 10/14 (71.4%) patients. Standard microbiology testing (SMT) revealed a pathogen or diagnostic marker of such in 8/14 (57.1%) patients. Notably, there were no instances in which mcfNGS detected a true pathogen in the context of negative SMT. Of the 14 patients with valid reports, clinical management was changed based on mcfNGS in 3 (21.4%) patients. This included addition of anti-fungal therapy, de-escalation of antimicrobials, and initiation of immunosuppressive corticosteroid therapy in the context of a negative mcfNGS result. Of the 10 patients in which at least one microorganism was detected, 70% were determined to be either contamination or of unclear clinical significance. There was only one instance in which mcfNGS alone led to a beneficial clinical impact as determined by de-escalation of anti-fungal therapy.

Figure 1.

mcfNGS was performed on 15 pediatric patients between July 2018 and April 2023. Pie chart represents categorization of mcfNGS results and their clinical impact.

Conclusion

While infectious disease metagenomic NGS holds great promise, the utility of currently available commercial assays for non-invasive specimens remains poorly understood. Here we report that in a small cohort of pediatric patients, commercial mcfNGS added minimal value over standard microbiological testing. Additional investigation is required to determine the ideal clinical picture warranting mcfNGS.

Disclosures

Jennifer Dien Bard, PhD, Abbott Molecular: Grant/Research Support|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|BioMerieux: Honoraria|Genetic Signature: Advisor/Consultant|Genetic Signature: Grant/Research Support|Luminex: Grant/Research Support|Salve: Stocks/Bonds|Thermo Fisher: Honoraria
557. Cost-effectiveness of Introducing Metagenomic Next-generation Sequencing (mNGS) for the Diagnosis of Suspected Neurological Infections Patients in China
Authors: Peng Siyang , Liang Rui , Liu Peng , Hu Long , Ai Yaping , Wang Junfeng , Hong Guanqi , Qu Shuli
Published: November 2023

Background

Early identification of neurological pathogens is crucial for favorable clinical outcomes. Metagenomic next-generation sequencing (mNGS) offers an alternative approach to identify pathogens in complex clinical samples. This study aimed to assess the cost-effectiveness of using mNGS in combination with traditional methods in diagnosing suspected neurological infections patients.

Methods

A decision tree model was developed to illustrate the clinical pathway for patients with suspected neurological infections in China. Two strategies were compared, one utilizing mNGS combined with traditional pathogen detection methods, and the other relying solely on traditional methods including cerebrospinal fluid microbial culture, smear microscopy, and serological tests. The study was conducted from the Chinese healthcare system perspective. Survival outcome, life years outcome and cost outcomes were captured over a lifetime horizon. Model inputs, including cost (specimen collection cost, diagnosis cost, imaging examination cost, drug cost and inpatient bed cost), treatment efficacy, mortality, sensitivity and specificity of different testing strategies, were derived from published literature and experts’ interviews. Uncertainty was assessed by sensitivity analyses.

Results

The base case analysis suggested that, compared with traditional pathogen detection methods, mNGS combined with traditional methods resulted in longer life-year (average 0.04 life-year gain) and lower cost (average saving of 6,419 CNY (947 USD)), among all patients tested. The life-years gain was primarily driven by the more accurate diagnosis and the consequent administration of more effective etiological treatment. The cost saving was largely driven by the reduction of drug costs which resulted from precision medicine-based treatment, instead of empirical treatment. The probabilistic sensitivity analysis confirmed the robustness of the model.

Conclusion

Compared to traditional methods only, mNGS combined with traditional methods is a cost-effectiveness method for improving patient clinical outcomes while reducing healthcare costs.

Disclosures

All Authors: No reported disclosures
561. Microbial Analysis and Fungi-Bacteria Correlation in Chronic Wound Infection Patients
Authors: Wang Qingqing , Hu Bijie
Published: November 2023

Background

Chronic wound infection has become a major healthcare burden globally. The colonized microbiome features and correlation between bacteria and fungi have not been listed.

Methods

In this study, we enrolled 38 acute wound infection and 28 chronic wound infection patients. The wound swabs sampling at admission were tested by metagenomic next-generation sequencing. Microbial community characteristics in wound infection patients and bacteria-fungi correlations in chronic wound infection patients were analyse after filtering background organisms.Figure 1.Flow chart

Results

We found that wound microbiome in chronic wound infection patients had higher abundance of Pseudomonas aeruginosa than that in acute wound patients. Meanwhile, microbes with high relative abundant in chronic infection wounds were less significantly association with plasma inflammation factors compared with those in acute infection wounds. Finally, we investigated the association between fungi and bacteria in chronic infection patients and found that relative abundance of Pseudomonas aeruginosa was negatively associated with that of Candida albicans.Figure 2.Comparison of bacteria species relative abundance between groups.Barplot of average relative frequencies of genera. Only genera>1% of relative abundance in wound were represented. C= chronic infection wound group, NC= acute infection wound groupFigure 3.Analysis of Linear Discriminant Analysis (LDA) Effect Size in groups.The bar graph showed pathogens with LDA score log10 >5 in two groups. C= chronic infection wound group, NC= acute infection wound group.Figure 4.Fungi-bacteria network in patients with chronic infection wound.Green dots: bacteria; Blue dots: fungi; red edge: positive correlation; green edge: negative correlation. Relative abundance of Pseudomonas aeruginosa was negatively associated with that of Candida albicans highlighted with red box.

Conclusion

Our metagenomic sequencing results of wound supported that Pseudomonas aeruginosa may be the biomarker of chronic wound infection and have interaction with candida albicans.

Disclosures

All Authors: No reported disclosures
562. Diagnostic accuracy comparison of the Biofire Filmarray pneumonia panel versus routine diagnostic methods for diagnosis of ventilator associated pneumonia: a real life study
Authors: García-Martínez Alejandra , Rojo-Gutiérrez Leticia , Llanes-Somellera Sergio , Aguilar-Zapata Daniel
Published: November 2023

Background

In Mexico, the Hospital Epidemiological Surveillance Network previously the COVID-19 pandemic, reported a total of 61,969 health care associated infections with an incidence rate of 4.7 per 100 discharges, 20.7% of which were categorized as ventilator associated pneumonia.

Biofire Filmarray pneumonia panel has been accepted as a tool for early and rapid diagnostic of pneumonia with recognition of several hospital acquired pathogens including resistant genes. However, there are some mismatch in the multiplex PCR detection and the culture isolation.

Methods

An observational, comparative, retrospective, non-randomized, cross-sectional, open study was performed using files from patients diagnosed with ventilator associated pneumonia who underwent diagnostic testing on culture and PCR multiplex FilmArray pneumonia panel to determine diagnostic accuracy.

Intensive care unit files from August 2021 to February 2022 with ventilator associated pneumonia with airway samples for Filmarray pneumonia panel and cultures. Evaluation of the used diagnostic tests was carried out using: sensitivity, specificity, positive predictive value and negative predictive value.

Results

55 patients were included, each of them with both test. 72% of the study population were males, with a mean age of 61 years. 76% of the population had severe COVID-19.

E.Coli had 100% sentitivity and 96% specificity , P. aeruginosa 100% sentitivity and 88% specificity, E.Cloacae 100% sentitivity and 91% specificity, and S. aureus had 100% sentitivity and 89% specificity on Biofire Filmarray pneumonia panel. While K. pneumoniae had 50% sensitivity and 89% specificity. NPV was 98% for K. pneumoniae, and 100% for E. coli, P. aeruginosa, E. cloacae, and S. aureus.

S.maltophilia was isolated in 3 culture samples and the Filmarray pneumonia panel was reported negative because lacking of testing this microorganism, as well as 1 A. fumigatus isolation.

Samples for cultures and Biofire FilmArray pneumonia panel

The different samples that were included from 55 patients in this study correlated with pneumonia panel and conventional cultures.

PCR Biofire FilmArray pneumonia panel diagnostic study evaluation

Each of the microorganism that had correlation between Filmarray pneumonia panel compared with conventional cultures

Conclusion

Biofire Filmarray pneumonia panel provides early and accurate information on pathogens causing ventilator associated pneumonia. However it cannot replace conventional culture because of lacking of some microorganism detection. It provides a useful tool for early decision-making in treatment.

Disclosures

All Authors: No reported disclosures
563. Mycoplasma genitalium with Fluoroquinolone Resistance: Design and Development of a Multiplex Real-Time PCR Assay for Detection and Differentiation
Authors: Alabyev Boris , Ankoudinova Irina , Scarr Noah , Decker Becca , Lukhtanov Eugene
Published: November 2023

Background

Mycoplasma genitalium is a sexually transmitted bacterium causing urethritis in men and associated with cervicitis and pelvic inflammatory disease in women. Only a few antimicrobial classes have activity against mycoplasmas. The first-line treatment for M. genitalium infections is doxycycline followed by azithromycin. Due to overuse of azithromycin to treat infections, resistance to azithromycin has been rapidly increasing. The moxifloxacin of fluoroquinolones family of antibiotics was 100% effective against M. genitalium, but recently the resistance markers for fluoroquinolone treatment have also emerged. Multiple studies attribute fluoroquinolone treatment failure to single nucleotide polymorphisms (SNPs) in parC and gyrA genes.

We aim to demonstrate proof of principle for a Real-Time PCR assay that simultaneously detects M. genitalium and fluoroquinolone resistance.

Methods

The MGB Alert M. genitalium with fluoroquinolone resistance RUO Detection Reagent is a multiplex of real-time PCR reagents that simultaneously detect M. genitalium DNA and distinguish fluoroquinolone resistance-associated mutations and wild type in M. genitalium. The assay targets parC and gyrA genes and includes a set of two primers and two probes specific to M. genitalium. The DSQ probe identifies the species DNA. The Pleiades hybridization probes serve to identify and distinguish a wild type genotype and several known resistance-conferring point mutations by melt curve analysis.

Results

Analytical Study:

Analytical sensitivity was determined and verified at 1.42 copy of bacterial genome per reaction.

A linear range was established from 1e7 to 10 genome copies per reaction.

Test results showed no cross-reactivity with organisms that might be present in normal vaginal swabs and urine specimens.

Conclusion

Preliminary analytical evaluation of the MGB Alert M. genitalium with fluoroquinolone resistance RUO Detection Reagent indicates potential as a valuable tool in the diagnosis of M. genitalium and resistance guided treatment.

Disclosures

Boris Alabyev, PhD, ELITechGroup MDx LLC: Salary Irina Ankoudinova, MS, ELITechGroup MDx LLC: Salary Noah Scarr, BS, ELITechGroup MDx LLC: Salary Becca Decker, BS, ELITechGroup MDx LLC: Salary Eugene Lukhtanov, PhD, ELITechGroup MDx LLC: Salary
564. Nocardiosis in Portugal: a single-center experience
Authors: Besteiro Bruno , Coutinho Daniel , Fragoso Joana , Figueiredo Cristovão , Nunes Sofia , Azevedo Carlos , Teixeira Tiago , Selaru Aurelia , Lameirão Angelina , Malheiro Luis
Published: November 2023

Background

Nocardiosis is a rare opportunistic infection with increasing incidence. Given its rarity, data on the prognosis and distribution are scarce and essential.

Methods

Retrospective study reviewing all nocardiosis cases diagnosed at our tertiary care hospital from January 2019 to January 2023.

Results

A positive Nocardia spp. culture was identified in 20 patients. Nocardia isolation was considered colonization in 2 patients, but the other 18 cases were considered as disease, 6 (33.3%) of which were classified as disseminated nocardiosis (DN). The mean

age was 64.0±14.05 years-old and 75% were males. One or more immunosuppressive conditions were identified in 70% of patients, including diabetes mellitus (n=9), active solid tumors (n=3), autoimmune diseases (n=3) and HIV infection with CD4+ < 200 cel/uL (n=2). Among the immunocompromised patients, 28,6% were being treated with high-dose corticosteroid therapy. The lung was the most common site of infection (85%) and most cultures were initially retrieved for lower respiratory tract samples (85%) evaluated for mycobacteria in modified Middlebrook 7H9 Broth. Lymphopenia was observed in 38.9% of patients.The most frequently isolated species were N.nova/africana (n=7), N.cyriacigeorgica (n=4) and N.pseudobrasiliensis (n=3). N.cyriacigeorgica was identified in the two cases considered colonization. Most patients (94.4%) were treated with antimicrobials, 50.0% in monotherapy and 44.4% in combination therapy. The most frequently prescribed antibiotics were co-trimoxazole (94.4%), imipenem (22.2%) and linezolid (16.7%). Selected antimicrobial agents were generally effective, with linezolid and co-trimoxazole having the highest susceptibility rates (100% susceptibility). The median [IQR] duration of treatment was 238 [45–720] and 170 [5–360] days for localized and DN, respectively. The overall one- year case fatality was 25% and was higher in patients with DN (80%).

Conclusion

Nocardiosis is an uncommon but emerging disease which can occur both in immunocompetent and immunocompromised patients. The present study reports a case series on Nocardiosis from Portugal and provides important information of this disease. As the

outcomes are poor, early recognition and prompt treatment are essential to improve the outcome.

Disclosures

All Authors: No reported disclosures
567. Performance of IgM and IgG antibodies against Bartonella henselae for diagnosis of Cat Scratch Disease in pediatric patients
Authors: Caratozzolo Ana M , Toledano Analía , Praino María Laura , Ferolla Fausto Martín , Neyro Silvina , Cazes Claudia Inés , López Eduardo L
Published: November 2023

Background

Bartonella henselae infection causes Cat Scratch Disease (CSD). Lymphadenopathy is the most common symptom and a small percentage of patients have systemic impairment. CSD can mimic malignancy and manifest atypically, therefore reliable serological testing has clinical importance. CSD is diagnosed if two of the following criteria are met: 1) the presence of clinical symptoms consistent with CSD; 2) the existence of antibodies against B. henselae IgM and/or IgG (1:256) (Fig.1). We aim to assess the accuracy and diagnostic utility of IgM and IgG in pediatric patients with suspected CSD.Fig. 1:Immunofluorescence AssayPositive IgM against B. henselae

Methods

A retrospective, observational and analytical study was carried out from April 2022 through April 2023. Medical and laboratory records of patients with follow-up in the Infectious Diseases Department of a Children's Hospital in Buenos Aires (Argentina) were evaluated.

Results

We included 244 serum samples from patients with clinical suspicion of CSD using Immunofluorescent assay (IFA).

Median age: 84 (IQR 48-132) months, 137 were female, 95% (233/244) had cat interaction.

Twenty eight percent (70/244) were diagnosed with CSD based on serological evidence: 83,9% (58/70) had IgM +/IgG + (group 1); 10% (7/70), IgM-/IgG+ >1/64 (group 2) and 7,15% (5/70), IgM+/IgG – (group 3). The average time of symptom onset was 22,8 (6-90) days for group 1, 29,4 (11-90) days for group 2, and 11,4 (5-15) days for group 3.

Lymphadenopathy was found in 87,1% (61/70) with or without systemic involvement and 6 % (4/70) had systemic involvement without lymphadenopathy.

IgM had Sensitivity: 89%, Specificity: 97%, Positive Predictive Value (PPV): 92% and Negative Predictive Value (NPV) : 96%.

Conclusion

Between 5-15 days after the onset of symptoms, IgM allowed us to diagnose 5 patients with CSD. The identification of IgM antibodies in CSD patients with systemic impairment has a great diagnostic performance. IgM remained positive after 90 days . We were able to diagnose CSD in 7 patients between 11 and 28 days following the onset of symptoms due to the presence of IgG 1:256 or higher. Combination of different methods (e.g., clinical and serological) and a correct time of sampling, greater than 5 days, should be considered for rapid and accurate CSD diagnosis.

Disclosures

All Authors: No reported disclosures
581. Impact of Urinary Antigen Tests on Clinical Outcomes in Patients Hospitalized with Community-acquired Pneumonia
Authors: Kern Marita , Israelsen Simone Bastrup , Benfield Thomas , Fally Markus , Ravn Pernille , Kolte Lilian
Published: November 2023

Background

Community-acquired pneumonia (CAP) is a common cause of hospital admission, with an annual incidence of 24.8 cases per 10,000 adults in the United States. To establish a microbiological diagnosis, most guidelines recommend using urinary antigen tests (UATs) in addition to respiratory samples in severe cases. However, it remains unclear how often these are used in clinical practice and with what impact. Therefore, we examined the impact of performing UATs on outcomes in patients hospitalized with CAP.

Methods

This was a multicenter cohort study of immunocompetent adult patients admitted with CAP at three hospitals in Denmark from 2017 to 2020. The primary outcome was 30-day mortality, while broad-spectrum antibiotic treatment and coverage for atypical bacteria comprised secondary outcomes.

We used logistic regression to examine the impact of UATs on patient outcomes and applied propensity-score matching to adjust for potential confounders.

Results

Of 2,449 patients included, 654 had UAT performed within 48 hours of admission. Of the tested group, 52/654 (8.0%) tested positive for Streptococcus pneumoniae.

30-day mortality was 11.8% in the tested group and 10.2% in the untested group (adjusted odds ratio [aOR] 1.17; 95% CI 0.83 - 1.65).

At discharge, 47.9% of the tested group received broad-spectrum antibiotics, compared with 42.4% in the untested group (aOR 1.25; 95% CI 1.00 - 1.55). Furthermore, 22.2% of the tested group had atypical coverage, compared with 21.9 % in the untested group (aOR 1.02; 95% CI 0.78 – 1.32).

Of patients with a positive pneumococcal UAT, 26.9% received broad-spectrum antibiotics at discharge, while 51.9% received broad-spectrum antibiotics in the UAT-negative group (aOR 0.34; 95% CI 0.15 – 0.77). Additionally, 21.2% of UAT-positive patients had atypical coverage at discharge, while 23.1% of UAT-negative patients had atypical coverage at discharge (aOR, 0.89; 95% CI, 0.35 – 2.26).

Forest plot for 30-day all-cause mortality

OR: Adjusted odds ratio; 95% CI: 95% confidence intervals; CRP: blood levels of C-reactive protein

Forest plot for treatment with broad-spectrum antibiotics at discharge

OR: Adjusted odds ratio; 95% CI: 95% confidence intervals; CRP: blood levels of C-reactive protein

Forest plot for coverage for atypical bacteria at discharge

OR: Adjusted odds ratio; 95% CI: 95% confidence intervals; CRP: blood levels of C-reactive protein

Conclusion

30-day mortality was similar between groups, whereas tested patients were slightly more likely to be treated with broad-spectrum antibiotics at discharge. Finally, patients with a UAT positive for S. pneumoniae less often received broad-spectrum antibiotics and coverage for atypical bacteria than UAT-negative patients at discharge.

Disclosures

All Authors: No reported disclosures
582. Comparing Broad-range PCR Testing and The Biofire® FilmArray® Pneumonia (PN) Panel in the Diagnosis of Bacterial Pneumonia
Authors: Khan Haseeba , Prabhudas-Strycker Kirsten , Samaro Matthew , Mellencamp Kagan A , Goings Michael , Boyd LaKeisha , Schneider Jack , Emery Christopher L
Published: November 2023

Background

Given the low sensitivity of conventional microbial isolation methods for identifying respiratory pathogens in bacterial pneumonia, target-specific syndromic multiplex real-time PCR panels have been used in conjunction with culture methods to improve diagnostic yield. Additionally, broad-range polymerase chain reaction (BR-PCR) targeting bacterial 16s rRNA conserved region has shown higher sensitivity with certain specimen types, so we sought to evaluate the clinical performance of BR-PCR performed on bronchoalveolar lavage (BAL) specimens in comparison to The Biofire® FilmArray® Pneumonia (PN) Panel (BioFire Diagnostics, Salt Lake City, UT, USA).

Methods

A retrospective chart review was performed on all BAL specimens that had both a PN panel test and BR-PCR performed from January 2020 to May 2022 at all Indiana University affiliated hospitals. The PN panel test was performed in-house as per laboratory protocol, while BR-PCR was performed in a reference laboratory. Outcomes assessed included turn-around times (TAT), sensitivity and specificity of BR-PCR and clinical impact, if any.

Results

A total of 68 BAL specimens from 53 patients were identified (83% of patients were immunocompromised). Percent positivity for the PN panel was 19% and that of BR-PCR was 18%. With the PN panel used as the gold standard, the sensitivity and specificity of BR-PCR was 85% and 98%, respectively. Only one respiratory organism was detected by BR-PCR but not by the PN panel, and it was not considered pathogenic or to have a significant clinical impact. The median TAT for the PN panel was 2.1 hours (1.8, 3.2) versus 7.8 days (6.9, 10.4) for BR-PCR.

Conclusion

In our cohort of patients, BR-PCR testing was not superior to the Biofire® FilmArray® Pneumonia (PN) Panel when used to detect certain bacterial etiologies of pneumonia. Additionally, faster TAT for the panel test has the potential to enhance antimicrobial stewardship practices by enabling better antibiotic utilization. Adjunctive BR-PCR testing may be useful for clinical care when conventional testing is negative and patients are at risk for a variety of potential pathogens, including fungi.

Disclosures

All Authors: No reported disclosures
583. Real-world Utilization of Serological tests in Patients with Suspected Scrub typhus in South Korea: A Single-center, Observational study
Authors: Kim SeulKi , Reum Kim A , Lim Seungjin , Lee Su Jin , Bae Moonsuk
Published: November 2023

Background

The most widely used diagnostic methods for scrub typhus are serological tests. We investigated the utilization of serological tests for scrub typhus in clinical practice and evaluated their clinical usefulness.

Methods

The data of all adult patients with suspected scrub typhus were collected who visited a tertiary-care hospital during the autumn season (between September and December) of the years 2019, 2020, and 2021. All included patients had an acute fever (axillary temperature 37.5) and had at least one of the following ten secondary findings: myalgia, nonspecific skin rash, eschar, headache, thrombocytopenia, increased liver enzymes, lymphadenopathy, hepatomegaly, splenomegaly, pleural effusion. Clinical diagnosis was independently adjudicated by two infectious diseases physicians and finally classified into two groups (1) scrub typhus and (2) other diseases. Two commercially available serological testing for scrub typhus were performed.

Results

We evaluated 172 patients with suspected scrub typhus; of them, 136 met the eligibility criteria, including 109 (33%) who were diagnosed with scrub typhus and 27 (67%) who were diagnosed with other diseases. The clinical characteristics between the groups are shown in Table 1. Single, paired total antibodies using immunofluorescence assay (IFA) testing, and total antibodies using immunochromatography (ICA)-based rapid diagnostic testing (RDT) were measured in 98%, 22%, and 75% of all patients, respectively (Table 2). The final laboratory confirmation using paired samples for scrub typhus was established at a median of 10 (IQR 9-15) days following the first visit day. The median follow-up time of all patients was 13 (IQR 8-19) days. The discrepancy between ICA results and clinical diagnosis was 26% for the scrub typhus group and 33% for the other disease group.

Conclusion

Serological testing currently used for scrub typhus in clinical practice in South Korea had limitations in clinical decision-making for scrub typhus.

Disclosures

All Authors: No reported disclosures