bluuebunny/crossref_metadata_2025_split huggingface dataset:
601. Clinical Presentation and Pregnancy Outcomes of PCR-Proven Rickettsial Infections in Pregnant Women
Authors: Yagel Yael , Yosef Tal schlaeffer , Shemer-Avni Yonat , Keren-Naos Ayelet , Nesher Lior 
Published: November 2023

Abstract

Background
Rickettsial infections are endemic zoonoses found worldwide. Spotted fever (R. conorii) and murine typhus (R. typhi) cause a spectrum of diseases from mild to multi-organ failure and death. Diagnosis and treatment of rickettsial infections in pregnancy are challenging, and little is known about pregnancy outcomes. We describe a cohort of PCR-proven rickettsial infections in pregnant women in Israel.

Methods
Whole blood samples were taken from pregnant women with acute febrile illness. Samples were subjected to DNA extraction and a general set of primers and probe was used to identify Rickettsia spp. by RT-PCR.

Results
In 2020, 12 pregnant women were diagnosed by PCR with rickettsial disease. Upon presentation, the mean age was 26 (18-39) years, and the mean gestational age was 31 (22-40) weeks. The number of days until diagnosis was established was 5 (2-10). The most common symptom other than fever was headache (11/12), only half presented with a rash. Most women developed elevated liver enzymes (11/12), and 2/12 had thrombocytopenia. Interestingly, 7/12 presented with respiratory symptoms, and 2/12 had myocardial involvement manifested as either elevated myocardial enzymes or ventricular dysfunction on echocardiogram. All women received Azithromycin as a first-line anti-rickettsial antibiotic, while 5 women were switched to Doxycycline due to disease severity. Defervescence within 24 hours after a single antibiotic dose was seen in 8/12 of women. Only 1/12 were delivered preterm, and the mean birth weight was 3000g. Serologic assays were available for 11/12 women, confirming murine typhi in 5/12 cases, and unidentified rickettsial infection in 3/12. Species identification wasn't available using PCR alone.

Conclusion
Molecular assays are a valuable tool for real-time diagnosis of rickettsial infections in pregnant women, allowing for a rapid targeted antibiotic treatment with good clinical outcomes for both mother and neonate. Unusual rates of respiratory and myocardial involvement were observed in our cohort, suggesting a possible specific pregnancy-related complication.

Disclosures
All Authors: No reported disclosures
609. Development of an Aspergillus Antigen Detection EIA
Authors: Bridges Nicole , Dailey Christopher , Hanzlicek Andrew , Wheat Joseph 
Published: November 2023

Abstract

Background
Aspergillosis is a mycosis caused by Aspergillus spp. Invasive infections are often life threatening in individuals with weakened immune systems. Detection of Aspergillus galactomannan by enzyme immunoassay (EIA) is the method used most to aid in diagnose aspergillosis. Here, we present the evaluation of a new antigen detection EIA, the MiraVista® Aspergillus antigen detection EIA (MVD EIA) and compare it with the Platelia® Aspergillus EIA.

Methods
Retrospective and prospective studies were conducted to evaluate the MVD EIA assay. The retrospective study consisted of bronchoalveolar lavage fluid (BALf) (n=44) from patients diagnosed with aspergillosis in accordance with EROTC guidelines. Controls(n=168) consisted of antigen negative specimens. A prospective study was conducted analyzing the agreement between the Platelia EIA and the MVD EIA. BALf and serum samples were evaluated and a receiver operator curve using Youden’s index was used to determine optimal diagnostic cutoff.

Results
The retrospective study using the MVD EIA in BALf demonstrated a sensitivity of 91% in and a specificity of 88%. The prospective study demonstrated a positive agreement between the MVD EIA and the commercial Platelia EIA of 90% and 96% for BAL and serum, respectively. The negative percent agreement was 97% and 96% respectively.

Conclusion
The retrospective study demonstrated that the MVD EIA is sensitive and specific when used with BALf. The prospective study demonstrated excellent agreement between the MVD EIA and the commercially available Platelia EIA. The use of this assay has the potential to aid in the diagnosis of aspergillosis.

Disclosures
Nicole Bridges, MA, MiraVista Diagnostics: Employee Christopher Dailey, PhD, MiraVista Diagnostics: Employer Andrew Hanzlicek, DVM, MiraVista Diagnostics: employee Joseph Wheat, MD, MiraVista Diagnostics: Ownership Interest|MiraVista Diagnostics: Ownership Interest
629. Malaria Screening Turnaround Time: Comparative Multicenter Analysis of Negative and Positive Results and Impacts of Rapid Diagnostic Test Implementation and Laboratory Centralization
Authors: LeBlanc Louiselle , Rosa Alexie , Martigny Didier , Lapointe Anne-Audrey , Ricard-Lacombe Antoine , Malick Mandy , Lévesque Simon , Martin Philippe , Provost Émile , Bélanger Stéphanie , Arsenault Christine 
Published: November 2023

Abstract

Background
Screening tests for malaria diagnosis should be reported rapidly because of its potential for rapid progression to severe disease and relatively high mortality. Guidelines recommend a high level of expertise for microscopy diagnosis and a laboratory test result turnaround time (TAT) ≤ 2 hours. Meeting these requirements can be challenging in the era of global laboratory centralization.

Methods
Multicenter retrospective cohort study comparing negative (2012-2021) and positive (2014-2023) malaria screening results within and between 2 central laboratories/tertiary academic centers in Quebec, Canada, in addition to data from one center’s primary care affiliated sites.

Results
1296 negative malaria tests were analyzed for complete analytical cycle TAT: Center A n=225 (central lab n=100; affiliated sites n=125), and Center B n=1120. After rapid diagnostic test (RDT) implementation, all sites have significantly reduced delays and ≤ 2h TAT compliance is &gt; 90% for central labs (median: A 38 min, B 53min). But affiliated sites’ compliance is low at 19.6% (median 6h12) with delays mostly attributable during transit between labs (median TAT from central lab sample intake is 25 min). Comparison of positive malaria result TATs to negative result TATs for both server lab centers will be presented, with a trend to longer delays to smear results for negative RDTs (median 4h13) vs positive RDTs (3h33). Detailed results from central lab – affiliated sites model will be presented with several practical recommendations. In preliminary results, no cases were diagnosed solely with thick smear, suggesting little added sensitivity in our center when used in addition to RDT + thin smear.

Conclusion
Quality and timely malaria diagnostic services are crucial for urgent clinical decisions given the potential for high morbidity and mortality. TATs are necessary lab quality management indicators during laboratory centralization and data for each component of malaria testing identifies weak links in the diagnostic chain. Such studies provide opportunities for quality and efficiency improvement, and for restructuring testing algorithms accordingly.

Disclosures
All Authors: No reported disclosures
631. Using a commercially available assay that measures cytomegalovirus (CMV)-specific CD4+ and CD8+ T-cell immunity to predict protection against CMV: Results from a prospective, blinded clinical trial
Authors: Almaghlouth Nouf K , Arvanitis Panos , Vieira Kendra , Farmakiotis Dimitrios 
Published: November 2023

Abstract

Background
Cytomegalovirus (CMV) infection is associated with significant morbidity and mortality among kidney transplant recipients (KTR). Given toxicities and costs of antivirals, there is growing interest in assays that measure CMV-specific T-cell immunity (TCI), which may predict protection against clinical infection. The Viracor® CMV TCI Panel (TCIP) uses flow cytometry and intracellular cytokine staining to measure %CMV-specific CD4+ and CD8+ T-cells; it is the only commercially available TCI assay in the US. In this investigator-initiated study, we evaluated the performance of the TCIP in predicting clinically significant CMV events. To our knowledge, this is the first prospective blinded clinical study of the TCIP.

Methods
We enrolled consecutive donor (D) or recipient (R) CMV seropositive KTR, who had TCIP testing monthly until either discontinuation of valganciclovir prophylaxis or the primary outcome. We also enrolled KTR with low-level untreated DNAemia, or after completion of valganciclovir treatment, to evaluate assay predictive values for progression or relapse of CMV infection, respectively. The primary outcome was CMV DNAemia (tested at the discretion of the treating provider for symptoms or laboratory findings), prompting treatment initiation. Secondary outcomes were any DNAemia and DNAemia &gt;1000 IU/mL. Treating providers were unaware of TCIP results.

Results
We included 46 KTR. Median age was 50.5 (range 18-74) years. 73.6% identified as men, 10.8% Black, 8.7% Hispanic; 41.3% had CMV D+/R- status. KTR with CMV events had significantly lower %CMV-specific CD8+ T-cells (Fig. 1A, p=0.024), and the CMV protection ROC AUC was significant (Fig. 1B: AUC 0.78, 95%CI 0.55-0.99, p=0.026). The positive predictive values of both CD4+ and CD8+ T-cell positivity &gt;0.2% for CMV protection were 96.3% (95%CI 81-99.9%) for the primary outcome, 92.6% (95%CI 75.7-99.1%) for any DNAemia, and 100% (one-sided 95%CI 87.2%) for DNAemia &gt;1000 IU/mL.Figure 1.A. Comparison of CMV-specific %CD8+ T-cells between patients with or without (protected) CMV events. B Receiver Operating Characteristic (ROC) curve for CMV protection.

Conclusion
The TCIP exhibited good performance in predicting protection from CMV events and could be a useful adjunct tool in clinical decision-making, regarding initiation or extension of CMV prophylaxis or treatment, as well as adjustments in immunosuppression.

Disclosures
Panos Arvanitis, MS, NIH: Grant/Research Support|NIH: Brown University Summer Assistantship program and from the Brown Emerging Infectious Disease Scholars (EIDS) (5R25AI140490) Dimitrios Farmakiotis, M.D., Astellas: Grant/Research Support|Merck: Grant/Research Support|Viracor: Advisor/Consultant|Viracor: Grant/Research Support
632. Characterization of Cytomegalovirus (CMV) Reactivation in Patients with Malignant and Non-Malignant Hematological Diseases at large Academic Center in Saudi Arabia
Authors: AlQahtani Hajar , AlShehri Bashayer , AlSuhaibany Nada , Alowais Shuroug , Alsulimani Mariam , Alyaqoub Majd , Alkhathran Lama , Alghanim Ameerah , AlQahtani Hessa , AlZahrani Mohsen , Bosaeed Mohammed 
Published: November 2023

Abstract

Background
The suppression of immune system in transplant patients increases the risk of Cytomegalovirus reactivation, which leads to higher rates of morbidity and mortality. Many risk factors have been identified to be associated with increased risk of CMV reactivation including mismatched human leukocyte antigen (HLA) transplant and myeloablative conditioning.

Methods
All patients =/ &gt; 14 years that underwent allo-SCT from April 2014 to April 2022 with complete medical records were included. Data collected include CMV serostatus, CMV viral load, time to CMV reactivation, conditioning regimen, use of in-vivo T-cell depletion for graft vs. host disease (GvHD)prophylaxis, and GvHD prophylaxis medications if used

Results
We included 404 patients with an average age of 29 years and 42% of female sex. Patients were divided into two different groups based on underlying disease for which All-SCT was indicated.183 patients (Group 1) underwent Allo-SCT for underlying hematological malignancy mainly acute myeloid leukemia (N= 64) and acute lymphoblastic leukemia (N=73) and remaining patients distributed between CML, Hodgkin and non- Hodgkin lymphomas. Others (N = 221) had sickle cell anemia and a plastic anemia. More than 75% of patients received myeloablative conditioning regimen in Group1 compared to Group2 were most patients received non-myeloablative regimen. Most patients received matched – related human leukocyte antigen (HLA). CMV seropositive recipients constitute 95% of all patients; 89% of patients experienced CMV reactivation within 13 days post SCT and had an average initial viral load of 51 IU during reactivation. 220 patients (62%) were able to clear CMV spontaneously within a median of 50 days post reactivation. 90 day non-relapse mortality and 1 years overall survival were 2.7% and versus 1.4% and 80% versus 94% in Group 1 and Group 2 respectively.

Conclusion
Our population is considered at higher risk of CMV reactivation due to the high prevalence of CMV seropositivity. Identifying factors that could contribute to CMV reactivation would help in identifying patients at highest risk and therefore, identify the best approach to manage CMV reactivation in those patients.

Disclosures
All Authors: No reported disclosures
662. Incidence and Treatment of Liver Abscesses in Ecuador. How Infection Source Control Delay Affects?
Authors: Salazar Grace Johanna , Dawaher Jesús , Peralta Amy , Borja Alejandra , Cóndor Verenice , Calucho Belén , Galarza Margarita 
Published: November 2023

Abstract

Background
Liver abscess is a frequent pathology poorly described in Ecuador. Treatment consists of drainage procedure and antibiotics for a recommended time between 4 to 6 weeks with a low evidence level, however, in other infections it is documented that source control can help decreasing treatment time.

Methods
A multicenter retrospective study was conducted in the public health system hospitals from Ecuador from January 2017 to December 2022. All cases of hospitalized liver abscess patients were included, calculating the incidence with regards to admissions. Demographic, microbiological isolation and treatment data were collected. The frequency of drainage procedure use, time of antibiotic use and length of hospital stay (LOHS) were evaluated. Means and Mann-Whitney U test were used for comparison. A p≤0.05 was considered statistically significant. SPSS version 25 software was used.

Results
With 162 cases, the incidence of the disease was 0.94 per 1000 hospital admissions. Sixty three percent of them were men (106), with an average age of 48 years old (15-91). The underlying causes were described in 33% of the cases. Drainage procedure was performed in 75% of the cases (122), most of them (80%) after the first 72 hours of hospitalization (mean 8.9: 0-35 days), so 84.5% received antibiotics prior to drainage procedure. Etiological microorganism was recovered in 20.9% of the cases (34). Etiology and susceptibility profile can be seen in figure 1. LOHS (19.7 vs. 10.5; p=0.0001; 95% CI 4.6-13.6) and antibiotic use (24.5 vs. 18.3; p=0.003; 95% CI 2.1-9. 9) were longer in patients who had drainage, however, these outcomes varied considerably depending on the time in which the drainage procedure was performed; if it was performed within the first 3 days, LOHS and antibiotic use were significantly lower (25.4 vs 10.6 p=0.0001) (28 vs 20.6: p=0.001; 95% CI 3.7-11.0). Figure 2.Figure 1.Etiology and susceptibility profile agents of liver abscess in Ecuador. January 2017 - December 2022.Figure 2.Comparison of antibiotic use days. Global Drainage versus no Drainage and less than 3 days Drainage versus no Drainage.

Conclusion
Our findings show that delaying the drainage procedure for liver abscess treatment decreases microbiological recovery, prolongs LOHS and the use of antibiotics. It is important to identify the reasons why there is no timely intervention in the public health system hospitals in the country to carry out improvement interventions. More studies are needed to optimize the treatment of this pathology.

Disclosures
All Authors: No reported disclosures
669. The clinical effectiveness of Fidaxomicin compared to Vancomycin in the treatment of Clostridioides difficile infection, a single center real-world experience
Authors: Alsoubani Majd , Chow Jennifer K , Rodday Angie Mae , Kent David , Snydman David R 
Published: November 2023

Abstract

Background
Clostridioides difficile infection (CDI) recurs in up to 25% of patients who achieve initial response to treatment. Therefore, the goal of treatment is to establish initial cure and prevent relapses. In this study, we examine the clinical effectiveness of fidaxomicin compared to vancomycin in a real-world setting.

Methods
This was a retrospective study conducted between 2011 and 2021 among patients who were treated with vancomycin or fidaxomicin for CDI at Tufts Medical Center. Patients were allocated to each treatment group if they received 72 hours of the agent. Patients less than 18 years, those who did not receive any treatment for CDI those treated with metronidazole only or fecal microbiota transplant were excluded. The primary study outcome was a composite of failure to achieve clinical cure within 72 hours of treatment initiation, relapse within 30 days following completion of initial treatment or death related to CDI. A secondary outcome of combined 30 and 90 day relapse was evaluated. A time to event analysis using a cause specific Cox proportional hazards model comparing the rate of the composite outcome in the two groups was conducted, accounting for the competing risk of death from other causes. Multiple imputation was used for missing variables but not the outcome.

Results
A total of 637 patients were diagnosed with CDI and able to be analyzed. There were 550 patients who received vancomycin compared to 87 patients who received fidaxomicin. Patients who received fidaxomicin were more likely to be female, have history of prior CDI and were on dialysis compared to those who received vancomycin (Table 1). The composite outcome occurred in 13 (14.9%) patients in the fidaxomicin group compared to 139 (25.3%) in the vancomycin group (Table 2). The adjusted hazard ratio for the composite outcome was significantly lower in the fidaxomicin group compared to vancomycin (HR 0.5, 95% CI 0.3-0.9) (Table 3). The adjusted risk of the secondary outcome, 30 and 90 day relapse, was reduced by 34% in the fidaxomicin group compared to vancomycin (HR 0.34, 95% CI 0.15-0.77).

Conclusion
Our analysis demonstrates that the use of fidaxomicin was associated with reduced hazard of CDI poor treatment outcomes. This study describes real world experience using fidaxomicin in patients with CDI.

Disclosures
Jennifer K. Chow, MD, MS, Kamada: Grant/Research Support|Merck: Grant/Research Support|Moderna: DSMB David Kent, M.D., M.S., W.L. Gore: Grant/Research Support David R. Snydman, MD, Merck: Advisor/Consultant|Merck: Grant/Research Support|Prolacta: Advisor/Consultant|Prolacta: Grant/Research Support|Seres therapeutics: Advisor/Consultant|Seres Therapeutics: Grant/Research Support|Summit Therapeutics: Grant/Research Support
676. Assessment of Sequential Testing for C. Difficile infections Utilizing Nucleic Amplification Test (NAAT) and Confirmatory Cytotoxic Assay on Diagnostic Stewardship Interventions
Authors: Johnson Jennifer L , Vizina Ann , Hempel Laura , Kuhn Ryan , Dhar Sorabh 
Published: November 2023

Abstract

Background
C. difficile infection (CDI) is a common health care-associated infection and quality measure for hospitals. The use of diagnostic stewardship interventions have been shown to decrease the rates of CDI by guiding appropriate testing using nucleic acid amplification tests (NAAT), which are highly sensitive but cannot differentiate between colonization and infection (i.e. lack clinical specificity). Cell culture cytotoxic assay (the “gold standard” test) has limited use in real time diagnosis, however may play a role in validating and augment the impact of diagnostic stewardship reductions in CDI.

Methods
This single center, retrospective review evaluated the utilization of a cytotoxic assay on clinical patient stool samples that met the criteria for diagnostic testing using NAAT as part of a diagnostic stewardship intervention for appropriate C. difficile testing. Samples that were positive for NAAT from 9/11/2018 to 4/11/2023 were concurrently sent for cell culture cytotoxic assay to verify the clinical suspicion of infection from C. difficile and the results reviewed by the multidisciplinary care and quality team for clinical correlation.

Results
Of the thirty-seven specimens that tested positive for CDI by NAAT, twenty-eight tested positive on the cytotoxic assay (a total 75.7% of specimen with positive NAAT had concordance with the cytotoxic assay). After clinical adjudication, a decrease of 13 days of therapy (DOT) for vancomycin, 3 DOT for fidaxomicin, and total cost saving of $739.50 was noted after adjustments to therapy. Average turnaround time for the cytotoxic assay was 7.1 days (SD = 3.8).

Conclusion
While limited as a real-time diagnostic assay for CDI, use of the cell culture cytotoxic assay validates the impact of diagnostic stewardship interventions and improves the specificity of testing when utilized in a sequential testing algorithm with NAAT.

Disclosures
All Authors: No reported disclosures
677. To Treat or Not To Treat: Patients with Clostridioides difficile PCR-positive/Toxin EIA negative Test Results
Authors: Yang Krista , Cooper Kaila , Stevens Michael , Bearman Gonzalo , Bryson Alexandra L , Doern Christopher , Silvia Munoz-Price L , Doll Michelle 
Published: November 2023

Abstract

Background
Diagnosis of C. difficile infection is complex; multiple diagnostic algorithms are used attempting to identify infected versus colonized patients. Management of symptomatic patients with PCR+ but toxin EIA- disease is controversial, as symptoms are non-specific. Our facility adopted an algorithm using PCR testing first, followed by EIA toxin testing for positive PCRs, in 9/2019. EIA- patients (who are PCR+) are reported as C. difficile negative by the lab. We compared outcomes of PCR- patients with those PCR+/EIA-.

Methods
We manually reviewed the patient records of all inpatients with reported negative C. difficile results from 9/1/22-11/15/22. Negative results were characterized as either PCR- or PCR+/EIA-. Treatment for a test result was defined as flagyl IV/PO, vancomycin PO, or fidaxomicin given within 7 days of the test (for any reason). We evaluated for repeat C. difficile testing, diagnosis of C. difficile infection (CDI), death in 60 days, and cause of death. We compared characteristics between patients with EIA+ versus negative status using Chi-square or Fisher’s exact testing in SAS 9.4.

Results
During the study, 321 inpatients had C. difficile tests performed that were reported negative. Of these, 267 were PCR-, and 54 were PCR+/EIA-. The proportion of patients treated did not differ between these groups (table 1, p=0.672). Of the 57 patients that had a repeat test within 60 days, 5 were classified positive (PCR+/EIA+): 2 from the PCR+/EIA- group and 3 from the PCR- group (p=0.065). One patient from the PCR- group subsequently had CDI diagnosed at another facility. Five patients in the PCR+/EIA- group and 32 in the PCR- group died within 60 days; C. difficile was not implicated in the deaths.

Conclusion
Treatment patterns and clinical outcomes in our facility were similar for patients with C. difficile PCR- and PCR+/EIA- diarrhea, in that few patients went on to develop PCR+/EIA+ disease.. Patients were from inpatient locations including bone marrow and solid organ transplant. Study limitations include sample size, and limited 60 day follow up. These data suggest that patients testing PCR+/EIA- may benefit from observation rather than immediate treatment, as 96% (52/54) may not go on to develop CDI. Our findings have implications for lab reporting and treatment of PCR+/EIA- results.

Disclosures
Christopher Doern, PhD, GeneCapture: Stocks/Bonds|Quidel: Advisor/Consultant|Shionogi: Honoraria Michelle Doll, MD, MPH, Molnlycke: Grant/Research Support