bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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
585. Development of a Monitoring System for Quality Assurance of Antibiotic Susceptibility Testing in a Microbiology Laboratory
Authors: Lim Gabriel Fang Yih , Lee Wendy Bee Leng , Lee Kar Mun , Low Yuan Shen , Ng Kang Ren , Lim Iris Sing Pei , Yang Huina , Chia Jonathan 
Published: November 2023

Abstract

Background
Antibiotic susceptibility testing (AST) procedures are sensitive to variations in testing conditions. Our diagnostic laboratory is compliant with recommendations set out in Clinical and Laboratory Standards Institute (CLSI) M100 (33rd edition) and M02-A12 (12th edition). A perceived increase in weekly quality control (QC) failures prompted the development of an electronic monitoring system for quality assurance of antibiotic susceptibility testing.

Methods
Zone size data for each antibiotic-organism QC combination were entered on Microsoft® Excel®, and formatted to generate graphs. The data were collected for at least 6 months before and after implementation. This monitoring system allowed the observation of trends which prompted further reviews of laboratory processes.

Results
Persistent recurrent borderline results reflected on the monitoring system sparked the implementation of systematic investigations into QC failures; a replacement program for QC strains; and standardization of incubation timings and desiccant usage. Using new American Type Culture Collection (ATCC) reference strains reduced the percentage of QC antibiotic-organism data which failed or were borderline, and led to greater consistency in testing (see Figure 1). Visual presentation of QC data triggered greater reflection. For instance, recurrent failures of ertapenem disks against Pseudomonas aeruginosa ATCC 27853 led to acknowledgement from the manufacturer that the loss of disk potency was due to the shipment of disks nearing the end of shelf life (see Figure 2). The trends in cefepime zone sizes against P. aeruginosa ATCC 27853 also prompted an internal review and these improved when antibiotic disk dispensers were consolidated to improve disk utilization (see Figure 3).

Conclusion
Systemic monitoring of QC trends is low cost and highlights issues which were previously not apparent. Standardization of practices and a systematic troubleshooting process have improved the quality of our disk diffusion susceptibility testing.

Disclosures
All Authors: No reported disclosures
595. Recovery of Clostridioides difficile Isolates from Cary-Blair Transport Medium Compared to No Transport Medium
Authors: Skinner Andrew M , Petrella Laurica A , Sambol Susan P , Johnson Stuart , Czaja Christopher A , Johnston Helen , Basiliere Elizabeth , Dhonau Robin , Korhonen Lauren C , Paulick Ashley , Adamczyk Michelle , Guh Alice , Gargis Amy , Gerding Dale N 
Published: November 2023

Abstract

Background
Surveillance of C. difficile infection (CDI), one of the most common U.S. healthcare-associated infections, is essential to inform public health response, characterize strains causing disease, and describe changes in strain prevalence over time. The U.S. CDC’s Emerging Infections Program (EIP) has conducted active CDI surveillance, including culturing of C. difficile from a convenience sample of stool samples from cases, since 2009. Cary-Blair transport medium (CBTM) is used by some clinical laboratories for stool testing, but little is known about its impact on the recovery of C. difficile from culture.

Methods
We performed a cross-sectional study of the recovery of C. difficile isolates from C. difficile positive stools received 10/2021 – 10/2022 from Colorado and Georgia EIP sites. Stools were collected and stored within CBTM or within no transport medium per site protocols and subsequently frozen. Frozen samples were thawed and inoculated on taurocholate-cycloserine-cefoxitin-fructose agar plates (TCCFA) for recovery. Specimens from which C. difficile was not recovered on TCCFA plates were subjected to alcohol shock to enhance the recovery rates. We compared the recovery rates of C. difficile from stools in CBTM and stools in no transport medium.

Results
We cultured 825 stools from Colorado and Georgia, recovering C. difficile from 81.5% of stools. Overall, 412 (49.9%) stools were in CBTM and 413 (50.1%) were stools in no transport medium. Of those with known testing data, 410/410 (100%) CBTM stools vs 371/407 (91.2%) non-CBTM stools were C. difficile positive by PCR test (p&lt; 0.01). Colorado stools accounted for 78% of the CBTM specimens. We recovered C. difficile on TCCFA plates from 59% (244/412) of stools in CBTM compared to 84% (348/413) in no transport medium (p&lt; 0.01). After including alcohol shock results, C. difficile was recovered from 72% of CBTM stools, and 91% from stools in no medium (p&lt; 0.01).

Conclusion
Cary-Blair transport medium may limit the recovery of C. difficile from culture and impact the ability to detect emerging strains. A large parallel study is needed to determine if these findings are reproducible and if stool collection methods should be standardized to maximize the recoverability of C. difficile by culture.

Disclosures
Andrew M. Skinner, MD, Academy for Continued Healthcare Learning: Honoraria|American Society of Healthcare Pharmacists: Honoraria|Ferring Pharmaceuticals: Honoraria|MJH Life Sciences: Honoraria Dale N. Gerding, MD, Destiny Pharma,: Advisor/Consultant|Sebela Pharma: Advisor/Consultant
600. Rapid Detection of Antibiotic Resistance Genes Direct from Whole Blood Samples by T2 Magnetic Resonance (T2MR®)
Authors: Wang Jin , Cacciatore Christopher , Snyder Jessica L , Noucas Heather , Smith Roger 
Published: November 2023

Abstract

Background
According to the Centers for Disease Control and Prevention (CDC), more than 2.8 million antibiotic-resistant infections occur in the US each year and more than 35,000 individuals die due to these infections. Rapid identification of drug resistance marker(s) in blood specimens may aid clinicians in getting patients on appropriate antimicrobial treatment early and decrease associated morbidity and mortality.

Methods
T2Resistance Panel is a qualitative, multiplex, T2MR assay designed to identify molecular markers of antimicrobial resistance in human whole blood specimens. The Panel detects thirteen molecular markers of resistance: blaKPC, blaCTX-M 14, blaCTX-M 15, blaNDM, blaVIM, blaIMP, blaOXA-48 Group, vanA, vanB, mecA, mecC, blaCMY and blaDHA. Bacterial isolates spiked into whole blood were used to evaluate analytical sensitivity, specificity and reactivity. When possible, testing utilized different bacterial species or gene variants. Assay performance was also assessed in the presence of potential interfering substances.

Results
The average time to result was approximately 3.5 hours. A Limit of Detection of &lt; 20 CFU/mL was demonstrated for all resistance markers. The assay successfully detected drug resistance markers from genetically and geographically diverse strains. There was no cross reactivity observed, and the presence of common interferents did not affect the detection of drug resistance markers.

Conclusion
The T2Resistance Panel is a rapid and sensitive assay that detects 13 antimicrobial resistance markers directly from whole blood specimens. Rapid detection of these resistance markers may allow clinicians to provide targeted and effective antimicrobial therapy earlier to patients.
This project has been supported in whole or in part with federal funds from the Department of Health and Human Services; Administration for Strategic Preparedness and Response; Biomedical Advanced Research and Development Authority (BARDA), under contract number 75A50119C00053. The findings and conclusions in this presentation have not been formally disseminated by the Department of Health and Human Services and should not be construed to represent any agency determination or policy.

Disclosures
Jin Wang, PhD, T2 Biosystems, Inc.: Stocks/Bonds Christopher Cacciatore, BS, T2 Biosystems, Inc.: Stocks/Bonds Jessica L. Snyder, Ph.D., T2 Biosystems, Inc.: Stocks/Bonds Heather Noucas, MS, T2 Biosystems, Inc.: Stocks/Bonds Roger Smith, Ph.D., T2 Biosystems, Inc.: Stocks/Bonds
611. Increased isavuconazole loading dosage yields earlier attainment of serum target concentrations in critical ill patients with extracorporeal membrane oxygenation
Authors: Hatzl Stefan , Kriegl Lisa , Posch Florian , Meinitzer Andreas , Schilcher Gernot , Eller Philipp , Grinschgl Yvonne , Muhr Tina , Hoenigl Martin , Krause Robert 
Published: November 2023

Abstract

Background
Invasive fungal infections (IFI) are a major threat for critical ill patients admitted to the intensive care unit (ICU). Isavuconazole is a triazole antifungal agent recommended for treatment of invasive aspergillosis or mucormycosis. Both IFIs might complicate influenza or COVID-19 in ICU patients. Treatment of acute respiratory failure in those patients may require extracorporeal membrane oxygenation (ECMO). The appropriate dosage of selected antifungal drugs in ECMO patients is of utmost importance for successful antifungal prophylaxis or treatment of IFIs. Isavuconazole plasma concentrations &lt; 1 µg/mL were reported in ECMO patients up to 24h after the first 200mg loading dose.

Methods
Critically ill ECMO patients receiving isavuconazole (first loading dose either 200mg, 300mg or 400mg, followed by isacuconazole administration as recommended) were included. Isavuconazole plasma concentrations were measured starting 2 h after the first isavuconazole loading dose up to 168 h.

Results
Out of 15 ECMO patients in total (median 62 years, range 47-64; 7 (47%) female) seven (46%) received standard isavuconazole loading regimen with 200mg as first dose, 3 (20%) received 300mg isavuconazole as first loading dose and 5 (34%) received 400mg isavuconazole as first loading dose. Twelve patients (80%) had veno-venous ECMO, 2 veno-arterial and one veno-arterial-venosus ECMO cannulation. The patients had a median paO2/FiO2 ratio of 76 (range 68-87) and sequential organ failure assessment score of 8.5. Three patients received isavuconazol for antifungal prophylaxis and 12 for treatment of IFI (Table 1). In comparison to patients receiving a first loading dose of 200mg or 300mg the median plasma concentrations in patients receiving the first loading dose of 400mg were significantly higher and constantly above 1µg/ml up to the first 24h. (Figure 1). No adverse effects related to isavuconazole were observed. No patient had isavuconazole concentrations ≥ 5µg/mL.
Isavuconazole plasma concentrations in ECMO patients
Isavuconazole plasma concentrations in ECMO patients at given timepoints after first isavuconazole dose. At dedicated isavuconazole administration timepoints, samples were obtained just before the next scheduled isavuconazole infusions.
Clinical and laboratory characteristics of the study population of 15 patients receiving isavuconazole and ECMO

Conclusion
Increasing the first loading dose of isavuconazole from 200 to 400mg led to a substantial increase in median isavuconazole plasma concentrations achieving ≥ 1µg/mL constantly after the first loading dose and was not associated with toxic side effects.

Disclosures
Robert Krause, MD, Pfizer: Grant/Research Support
612. Coccidioidal Pulmonary Cavitation: A New Age
Authors: Kooner Lovedip , Garcia Austin , Kaur Akriti , Sharma Rupam , Bustamanate Virginia , Narang Vishal , Berjis Amir , Munoz Augustine , Thompson George R , Kuran Rasha , Johnson Royce H , Heidari Arash 
Published: November 2023

Abstract

Background
The majority of literature on cavitary pulmonary coccidioidomycosis is from four decades ago which was prior to the advent of triazoles and focused on surgical treatment. This observational study is a comprehensive retrospective study of pulmonary cavitary coccidioidomycosis from patients at Valley Fever Institute at Kern Medical over the last 12 years. This observational study aims to explore the spectrum of coccidioidal cavities and the evaluation and management of those cavities.

Methods
IRB approved, retrospective review of electronic medical records of the Valley Fever Institute database was conducted. Demographics, comorbidities, types, and the number of cavities, complications, and medical and surgical treatment were gathered and compared to the literature. PubMed and Google Scholar were searched for cavitary pulmonary coccidioidomycosis

Results
Of the initially 276 identified patients, 137 met the inclusion criteria. This study found 52 (37.2%) patients with hemoptysis. One case (0.7%) required radiologic intervention to occlude the bleeding vessel, and one (0.7%) case of hemorrhage required right upper lobe lobectomy. Nine (6.6%) cases exhibited a ruptured cavity. Eight of those cases had initial chest tube placement, of which three (3/8, 37.5%) did not require surgical intervention. Seven of 137 (5.1%) cases presented with a pleural effusion not associated with a cavity rupture. Five (3.7%) were due to primary coccidioidomycosis. Three of the coccidioidal effusions required therapeutic thoracentesis, and none required a chest tube or surgery. The mean duration of the initial antifungal treatment was found to be 563 days (n=80). In 35% (28/ 80) of them, a triazole was switched to another triazole for variable reasons, including treatment failure or side effects.

Conclusion
Coccidioidal pulmonary cavitation remains a complex disease to evaluate and treat. This study's ethnic demographic differed from other cohorts. It also contradicts the notion that pulmonary coccidioidal cavitary disease and dissemination infrequently manifest in the same patient. In the present age of triazole therapy, indications and the need for surgery continue to decline. Further investigation needs to be conducted to evaluate medical therapy’s efficacy and long-term outcomes.

Disclosures
Rupam Sharma, PGY-1/MD, Astellas: Grant/Research Support George R. Thompson, III, MD, Astellas: Advisor/Consultant|Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Grant/Research Support|F2G: Advisor/Consultant|F2G: Grant/Research Support|Mayne: Advisor/Consultant|Mayne: Grant/Research Support|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Mundipharma: Advisor/Consultant|Mundipharma: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support