bluuebunny/crossref_metadata_2025_split huggingface dataset:
544. Outpatient Remdesivir Use at a Stand Alone Children's Hospital
Authors: Rodriguez Brittany , Stimes Grant T , Hilliard Tanya J , Satter Lisa Forbes , Munoz Flor M 
Published: November 2023

Abstract

Background
When remdesivir was approved for non-hospitalized, high-risk patients with mild to moderate COVID-19, Texas Children’s Hospital (TCH) implemented an outpatient clinic for eligible patients to receive remdesivir infusions. There are limited data evaluating the use of outpatient remdesivir in pediatric patients. We describe the clinical characteristics and outcomes of the patients treated with outpatient remdesivir at TCH.

Methods
Patients that were referred to receive outpatient remdesivir from June 7, 2022 to April 5, 2023 were included. Information collected includes demographics, comorbidities, refusal reason, adverse events, emergency center (EC) visit or admission within 14 days after final dose, and EC visit or admission within 14 days of referral if patients did not receive remdesivir. Chi-square was used to determine differences between the groups.

Results
There were 187 patients referred during the study period. The median age of all referred patients was 8.8 years (IQR 4.84-12.96 years). The median time from reported symptom onset to dose 1 of remdesivir was 2 days (IQR 1-4 days). The comorbidities of all patients are listed in Figure 1. Out of the 182 patients, 69 patients (37.9%) received remdesivir, 10 patients (5.5%) were admitted prior to receiving their first dose, and 107 (58.8%) were not treated. The most common refusal reason was improvement between the referral and treatment evaluation visit (Figure 2). Among those treated, 8 patients (11.6%) visited the EC resulting in 7 admissions (10.1%) within 14 days of their last dose of remdesivir, while 7 patients (6.5%) that were referred but did not receive remdesivir visited the EC resulting in 3 admissions (2.8%) within 14 days of their referral being placed (p=0.04). More serious underlying conditions (e.g. immunosuppression, chronic lung disease, etc.) were more common among treated patients vs. untreated patients (p=0.00002).

Conclusion
Outpatient remdesivir was well tolerated among pediatric patients. In our series, the majority of high- risk patients receiving outpatient remdesivir treatment did not require subsequent EC visit or hospitalization. More robust data are needed to determine the clinical efficacy of this treatment for pediatric patients in the outpatient setting.

Disclosures
Lisa Forbes Satter, MD, ADMA: Advisor/Consultant|CsL Behring: Advisor/Consultant|Grifols: Advisor/Consultant|incyte: Advisor/Consultant|Pharming: Advisor/Consultant|Takeda: Advisor/Consultant Flor M. Munoz, MD, MSc, CDC respiratory virus surveillance: Grant/Research Support|Gilead: Grant/Research Support|Moderna, sanofi, aztra zeneca, Merck, GSK: Advisor/Consultant|NIH: DSMB|NIH COVID-19 vaccines in pregnancy: Grant/Research Support|Pfizer Pediatric COVID-19 vaccines: Grant/Research Support|Pfizer, Dynavax, Monderna, Meissa, NIH: DSMB
558. Cost-effectiveness of Introducing Metagenomic Next-generation Sequencing (mNGS) for the Diagnosis of Suspected Respiratory Infections Patients in China
Authors: Peng Siyang , Liang Rui , Mao Sheng , Tang Wen , Tang Mi , Ai Yaping , Wang Junfeng , Hong Guanqi , Qu Shuli 
Published: November 2023

Abstract

Background
Early identification of respiratory 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 respiratory infections patients.

Methods
A decision tree model was developed to illustrate the clinical pathway for patients with suspected respiratory 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 bronchoalveolar lavage 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 0.18 life-year gain) and lower cost (average saving of 3,069 CNY (453 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
559. Results of the implementation of a molecular pneumonia panel at a hospital in the Dominican Republic: expanding the scope of detection and management
Authors: Guzman-Marte Anel E , Rojas-Fermin Rita A , Hernandez-Landa Ricardo Ernesto , Reyes-Batista Ledis , Camilo Glennys S 
Published: November 2023

Abstract

Background
Lower respiratory tract infections (LRTIs) have been associated to significant morbidity and mortality. Conventional microbiology methods often fail to identify the etiological agent due to lack of sensitivity or viral or fastidious pathogens. Pneumonia molecular diagnostics is able to expand the scope of pathogens detected, therefore, we describe our experience in the incorporation of this method, the difference in etiological identification and clinical decision making.

Methods
We performed a retrospective cohort study of 75 patients with Filmarray pneumonia panel from November 2020 to September 2022. We described demographics, co-morbid conditions, outcomes and correlation with standard cultures in patients who were admitted with LRTI at the Hospital General de la Plaza de la Salud, a 289-bed tertiary teaching hospital in the Dominican Republic.

Results
Amongst the 75 patients, 56.6% were male and the average age was 51 years old. The most common comorbidities were diabetes mellitus (81.6%), hypertension (40.8%) and nephropathy (10.5%). The panels had a positivity rate of 74.6% (56/75) versus a 35% (14/40) seen in cultures. The most frequent microbial targets detected were S. aureus (18%), P. aeruginosa (14,3%) and K. pneumoniae group (10%) and at least one antimicrobial resistance gene was detected in 50% (28/56), distributed as MecA/C and MREJ (35%), CTX-M (38%), KPC (10%), NDM (10%), VIM (8%), IMP (8%) and OXA-48 like (3%). A positive culture was most likely to occur when the number of copies/mL in the panel was ≥ 10˄5 (p-value &lt; 0.001). A viral target was detected in 21 patients (28%) alone or coinfecting with a bacterial agent.

Conclusion
Not only did the pneumonia panels allow an earlier detection of the etiological agent, but they also identified more pathogens compared to cultures. This enabled targeted management by reducing the unnecessary use of antimicrobials as well as activating infection control measures when necessary (i.e Influenza). The results seen in this study, along with the expanded scope of pathogens detected, will definitely serve as an update into our current LRTI hospital guidelines.

Disclosures
All Authors: No reported disclosures
565. Antimicrobial susceptibility profiles of Acinetobacter species in blood: 10-year experience from a major United States reference laboratory
Authors: Bisono Garcia Bismarck S , Ranganath Nischal , Streck Nicholas , Schuetz Audrey N , Shah Aditya 
Published: November 2023

Abstract

Background
Antimicrobial resistance (AMR) is a threat to healthcare, and infections with antimicrobial resistant organisms carry significant morbidity and mortality. Owing to high rates of AMR, the Centers for Disease Control and Prevention listed Acinetobacter baumannii as a top priority pathogen for research and development of new antimicrobial agents. Antimicrobial susceptibility testing is challenging for this organism, and susceptibility profiles are variable, leading to need of a potential guidance document with assistance in selecting effective empiric therapeutic regimens.

Methods
We retrospectively reviewed the microbiology and antimicrobial susceptibility testing (AST) results for Acinetobacter spp. from blood culture isolates submitted to Mayo Clinic Laboratories from December 2012 to 2022. AST was performed using agar dilution and interpretations following Clinical & Laboratory Standards Institute (CLSI) guidelines. Isolates were identified by MALDI mass spectrometry and/or 16S sequencing, as available (Figure 1).Figure 1:Isolate identification
Isolate identification description. Isolates were analyzed based on this classification used in out laboratory.

Results
804 blood culture isolates were included. A. baumannii/calcoaceticus complex (27%) was most frequently isolated, followed by A. lwoffii (22%), and showed the highest resistance across all antimicrobials (73% susceptible or below) (Figure 2). A. baumannii/calcoaceticus complex showed rising resistance rates over time from 2012 to 2022 for meropenem, minocycline and ampicillin-sulbactam (Figure 3). Cefiderocol non-susceptible rate was 35% for A. baumannii/calcoaceticus complex.Figure 2:Antimicrobial susceptibility profiles for Acinetobacter spp.
Description of susceptibility profiles for Acinetobacter spp. isolates, based on the classification used by our laboratory. Antimicrobials are presented at the top and isolates on the left. Number of isolates analyzed are presented in the table with the percentage of the isolates susceptible to each antibiotic class in parenthesis.Figure 3:Acinetobacter baumannii/calcoaceticus complex isolates and resistance, trend
Trend of isolates per year and resistance percentage to meropenem, colistin, minocycline and amp-sulb. Number of isolates per year at the base of each bar; percentage of resistance for antimicrobials expressed on lines. Amp-sulb = ampicillin-sulbactam.

Conclusion
A. baumannii/calcoaceticus complex showed high levels of resistance ( &gt;75%) across multiple antimicrobials and increasing rates of resistance over time from 2012 to 2022. A high number of cefiderocol non-susceptible organisms is also concerning (Figure 2).

Disclosures
Audrey N. Schuetz, MD, Merck: Advisor/Consultant
569. Utility of Repeat Molecular Diagnostic Testing in the Laboratory Diagnosis of Pulmonary Tuberculosis
Authors: Chia Jonathan 
Published: November 2023

Abstract

Background
Molecular diagnostic methods are commonly used to supplement microscopy and culture in the rapid diagnosis of pulmonary tuberculosis (TB). While international guidelines recommend the collection of multiple sputum samples for microscopy and culture due to their low sensitivity, the utility of performing multiple molecular tests is less well-defined. A retrospective analysis of molecular diagnostic testing in a high pre-test probability population was conducted to determine the impact of repeated testing on achieving diagnosis.

Methods
A review of 10406 requests for Mycobacterium tuberculosis polymerase chain reaction (PCR) testing, originating from the TB contact screening and treatment clinic of a national Infectious Diseases specialist centre, was conducted for the period of 1 Jan - 31 Dec 2022. 5336 patients with valid test results were identified. (Table 1)
PCR testing was performed using the Xpert® MTB/RIF (Cepheid) PCR assay, either in the clinic as a point-of-care test, or in the hospital’s microbiology laboratory. Acid-fast microscopy was performed in the microbiology laboratory using a combination of fluorochrome and Ziehl-Neelsen staining, while cultures were referred to a Biosafety Level 3 laboratory at another institution for culture and susceptibility testing using the Mycobacteria Growth Indicator Tube (MGIT) system.Table 1:PCR testing ordered by a tuberculosis contact screening and treatment clinic in 2022

Results
Out of 5336 patients identified, 4540 (85.0%) had 2 or more PCR tests performed within the first month of their initial encounter.
443 patients (8.3%) tested PCR-positive in total. 385 tested positive on their first test; further tests after the first identified another 58 cases. Compared to cumulative culture results, the sensitivity and specificity of the first PCR test performed in the target population was 65.2% and 98.3% respectively, with a negative predictive value (NPV) of 96.8%. Repeat PCR testing increased sensitivity to 69.3% and NPV to 97.5%. (Tables 2 and 3) 74 initially-negative patients would need to be retested to identify an additional PCR-positive case, with potential costs of SGD $14,504 per case ($196 per test).Table 2:Comparison of single PCR test performance against cumulative mycobacterial culturePPV = Positive Predictive Value NPV = Negative Predictive ValueTable 3:Comparison of repeated PCR test performance against cumulative mycobacterial culturePPV = Positive Predictive Value NPV = Negative Predictive Value

Conclusion
For purposes of resource allocation, rationalisation of repeat testing in the diagnosis of pulmonary TB should be considered as an alternative to routine retesting, even in a high-risk population.

Disclosures
All Authors: No reported disclosures
571. Development of a Multiplexed PCR Assay for the Detection and Differentiation of Non-Tuberculosis Mycobacteria (NTM)
Authors: Cowden Scott , Grantham James , Davidson Jerod , Lute Emily , Nutt Jamie , Bixler Ellis , Kleiboecker Steve 
Published: November 2023

Abstract

Background
Current NTM diagnostics rely on a combination of testing modalities including clinical presentation, radiology, and culture. NTM cultures often have extended turnaround times. Additionally, the importance of discriminating etiological agents in the Mycobacterium avium complex (MAC) and Mycobacterium abscessus complex (MAbC) due to increasing drug resistance is now recognized. Here we describe the development of real-time PCR assays targeting members of the MAC and MAbC responsible for NTM infections. The objective was to develop a rapid diagnostic assay for the detection of pathogenic NTM directly from patient blood and sputum.

Methods
The MAC qPCR assay design allows for non-specific yet inclusive detection of M. avium subsp. avium, hominissuis, paratuberculosis, and sylvaticum, M. intracellulare, M. intracellulare subsp. chimaera and M. colombiense. The MAbC assay allows for inclusive and differential detection of M. abscessus subsp. abscessus, bolletii and massiliense. MAC and MAbC designs were screened to identify candidates and were then multiplexed with an internal control assay. Performance was evaluated in spiked whole blood and sputum.
DNA was extracted using the MagMAX™ DNA Multi-Sample Ultra 2.0 Kit and KingFisher™ Flex system (Thermo Fisher). Amplification was performed using TaqMan™ Fast Advanced Master Mix (Thermo Fisher) and the Applied Biosystems™ 7500 Fast instrument.

Results
Linear regression of plasmid standards for assays targeting MAbC-specific gene targets produced R2 values &gt;0.99 and slopes ranging from -3.39 to -3.35 (97-99% efficiency). Linear regression of standards for assays targeting MAC-specific gene targets produced R2 values &gt;0.99 and slopes ranging from -3.47 to -3.35 (94-98% efficiency). Assay specificity was determined by challenging the assays with NTM’s outside of each respective complex as well as other common bacterial pathogens.

Conclusion
Development of NTM PCR assays to detect and differentiate slow growing Mycobacteria aids in rapid diagnosis and provides insight into selection of appropriate antibiotic therapies. The assays described here exhibit excellent linearity, specificity, inclusivity and with additional development will provide a reliable means of detecting and differentiating relevant NTM species.

Disclosures
Scott Cowden, MS, MB ASCP(CM), Eurofins Viracor: Employee James Grantham, n/a, Eurofins Viracor: Employee Jerod Davidson, n/a, Eurofins Viracor: Employee Emily Lute, n/a, Eurofins Viracor: Employee Jamie Nutt, n/a, Eurofins Viracor: Employee
573. Creation of a Statewide Ambulatory Urinary Antibiogram and Evaluation of Regional and Temporal Variation in Antibiotic Susceptibility
Authors: Curanovic Dusica , Chin Jacinta , Garcia Chris , Wright Catherine , Stainback Rita , Martin Melissa , Naccache Samia , Smith Kristen , Engler Howard , Flett Kelly 
Published: November 2023

Abstract

Background
Empiric antibiotic selection in outpatient care often relies on inpatient antibiograms which may not accurately reflect ambulatory susceptibility rates. To address this, Novant Health (NH) and Labcorp analyzed urine culture results from North Carolina (NC) to create an ambulatory antibiogram and assess temporal and regional differences.

Methods
Cross-sectional study of urine culture data collected 1/1/20-12/31/21 from ambulatory sites in NC. Testing and antibiogram preparation were performed at Labcorp (Burlington, NC) based on CLSI guidelines (M100 S28). Pediatric and adult data were compiled separately. NH and state-wide data were analyzed using the chi-square or Fisher exact test with Bonferroni correction for multiple comparisons.

Results
In 2021, Escherichia coli was the most common isolate for NH (n=18937 adult, n=624 pediatric) and state-wide (n=87,226 adult; n=2696 pediatric). E. coli was ≥ 80% susceptible to all tested antibiotics except ampicillin; Klebsiella pneumoniae was ≥ 80% susceptible to all except nitrofurantoin; and Proteus mirabilis/penneri was ≥ 80% susceptible to all antibiotics tested. Susceptibility rates were similar between NH and state-wide data except for lower susceptibility to ceftriaxone (94% vs 95%; p&lt; .001). Compared to 2020, state-wide adult E. coli isolates from 2021 had increased susceptibility for amoxicillin/clavulanic acid (86% vs 85%), ampicillin (60% vs 59%), cephalosporins (84-93% vs 82-92%), and quinolones (87% vs 86%) (p&lt; .001 all). NH isolates did not show significant changes. Susceptibility rates by region were similar, except for lower susceptibility to cefuroxime among adult E. coli isolates in the Triad region relative to state-wide (82% vs 84%; p&lt; .001). No significant temporal or regional differences in susceptibility were observed for K. pneumoniae, Proteus spp., P. aeruginosa, and among pediatric samples.

Conclusion
Susceptibility data were largely similar in NH vs. state-wide data, and between regions. Small but statistically significant temporal changes were found in state-wide data. Overall, our results support use of a state-wide antibiogram to inform treatment choices across all regions and within specific healthcare systems.

Disclosures
Dusica Curanovic, PhD, Labcorp: employed by labcorp during study|Labcorp: Stocks/Bonds Chris Garcia, MD, Labcorp: Prior employee|Labcorp: Stocks/Bonds Catherine Wright, PhD, Labcorp: Employee|Labcorp: Stocks/Bonds Rita Stainback, MS, MT (ASCP) SM, DLM, Labcorp: Employee|Labcorp: Stocks/Bonds Melissa Martin, BS, Labcorp: Employee Samia Naccache, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds Kristen Smith, PhD, bioMerieux: Employee|Labcorp: Stocks/Bonds Howard Engler, PhD, D(ABMM), Labcorp: Employee|Labcorp: Stocks/Bonds
574. Daily Antibiotic Utilization Prescription Audit in the Infectious disease (ID) and Non-ID Department in Hospitalized Patients: A Prospective Case-Control study in a Teritiary care hospital
Authors: Dorairajan Suresh Kumar , Pavithra G , Hari Nivetha , Angel Jenifer F , Vijayakumar Oviya , Eiphan Kezia V 
Published: November 2023

Abstract

Background
Antimicrobial prescription audits were often carried out to reduce the overuse of antibiotics. Usually, audits were performed over periodical intervals. Daily antibiotics audits were time consuming and labour intensive. Though it"s practically impossible, we tried. However, we conducted this audit over a three-month period as daily audit and the cases were regularly followed. It is the prospective case-control study of antibiotic utilizations from prescriptions on ID and non-ID department.

Methods
This Prospective Case-Control study was conducted in tertiary care hospital in India for a period of 3months (Jan-mar2023). Data regarding demographics, antibiotic therapy, diagnosis, rational antibiotic usage (indications mentioned or not), type of therapy (surgical prophylaxis, definitive and empirical therapy) and 48hrs review of antibiotic prescriptions (escalation, de-escalation, continuation and dis-continuation therapy) of both groups were collected by Pharm-D interns from the medical records and analysed using SPSS version 26.0.

Results
During the study period, 899 subjects’ medical records were audited for antibiotic usage from the prescriptions. The comparative data were shown in table-1.

Conclusion
1/3rd of the cases acquired ID opinion which is significantly less than the non-ID department. Predominantly ID opinion is acquired when culture shows positive results. In most cases, the indications were mentioned only by the ID and not by the non-ID team. Discontinuation (28.1%) and de-escalations (18.7%) done by the ID was found to be significantly higher than non-ID. Based on this, we conclude that ID opinion play a crucial role in selection of antibiotics, both in terms of definitive and empirical choices. This study has certain limitations where, outcomes will be followed further.

Disclosures
All Authors: No reported disclosures