bluuebunny/crossref_metadata_2025 huggingface dataset:
531. Clinical efficacy of inhaled corticosteroids in patients with coronavirus disease-2019: an updated systematic review and meta-analysis
Authors: Jeong Su Jin
Published: November 2023

Background

Inhaled corticosteroids (ICS) are known to be relatively safe for long-term use in inflammatory respiratory diseases, and it has been repurposed as one of the potential therapies for outpatients with coronavirus diseases 2019 (COVID-19). However, ICS have not been accepted for COVID-19 as a standard therapy because of its lack of proven benefits. Therefore, this study aimed to evaluate the effectiveness of ICS in patients with COVID-19.

Methods

Randomized controlled trials comparing the efficacy of ICS treatment in patients with COVID-19 were identified through literature electronic databases searches up to March 10, 2023. Meta-analyses were conducted for predefined outcomes, and the certainty of evidence was graded using the grading of recommendations, assessment, development, and evaluation approach.

Results

Overall seven trials (eight articles) were included in this systematic review. Compared with usual care, ICS was associated with significantly improved clinical recovery at 7 and 14 days in patients with COVID-19. In subgroup analysis, only budesonide showed significant efficacy in clinical recovery, whereas no significant benefit was observed for ciclesonide. Moreover, ICS use was not significantly associated with all-cause hospitalization, all-cause mortality, admission to intensive care unit, or the use of mechanical ventilation. Our systematic review used evidence with very low to moderate certainty.

Conclusion

The results of this meta-analysis revealed the clinical efficacy of ICS treatment compared with usual care. Based on limited evidence, our results suggest that ICS treatment, especially budesonide, improves the clinical recovery of patients with COVID-19. The safety of ICS treatment in patients with COVID-19 has not yet been established; however, ICS are relatively safe and widely available. In addition, short-term ICS use in the early stages of COVID-19 did not increase the risk of pulmonary infections or side effects. Subsequent randomized clinical trials with a larger number of patients, as well as meta-analyses, are needed to determine the usefulness of ICS treatment in improving the clinical outcomes of patients with COVID-19.

Disclosures

All Authors: No reported disclosures
572. Growth rate comparisons for clinical Klebsiella pneumoniae (KP) isolates using nutrient-rich and -depleted broth stratified by inner colony production during fosfomycin (FOF) disk diffusion (DD) testing
Authors: Daley Ellora , Bixby Morgan , Collins Lindsey , Salay Jenna , Hirsch Elizabeth B
Published: November 2023

Background

Recent studies have indicated the presence of non-susceptible IC appearing within the zone of inhibition during FOF DD testing. Limited studies focusing on Escherichia coli have demonstrated that observed increases in resistance come with decreased isolate fitness. We sought to compare growth rates of susceptible KP non-IC-producers, IC-producers, and their non-susceptible IC (as determined by broth microdilution) in both nutrient-rich and -depleted broth to understand in vitro fitness differences.

Methods

Two isolates which had never produced IC (254, 275), two susceptible IC-producers (131, 209), and two corresponding resistant IC (131D, 209D) were included. Each isolate was grown in both full and ¼ strength Mueller-Hinton broth (MHB) for 24 hours with samples taken at standard time intervals in two technical replicates, with duplicates performed on separate days. Using the generation time equation (Figure 1) for the logarithmic phase of growth, rates were calculated and compared across three groups: (1) individual parent and IC pairs, (2) non-IC producers and IC-producers, and (3) IC-producers and IC as a whole. Comparisons across the three groups in both nutrient-rich and -depleted conditions were completed using Student’s t-tests.

Results

Average generation time for each isolate in full and ¼ strength MHB are shown in Table 1. Difference in generation time in full-strength MHB for parent and IC pairs were [131/131D] 0.04 hours and [209/209D] 0.05 hours (Table 2). In ¼ strength MHB, difference in generation time for parent and IC pairs were [131/131D] 0.03 hours and [209/209D] 0.01 hours. Average growth rate difference between non-IC-producers and IC-producers was 0.05 hours and 0.01 in full- and ¼ strength, respectively. The average generation time difference between IC-producers and IC was < 0.01 hours and 0.01 in full- and ¼ strength, respectively.

Conclusion

Our data reveal no significant difference in growth rates between these KP isolate types which may signify no in vitro fitness differences for IC or IC-producers in both nutrient-rich and nutrient-depleted conditions. While the findings of this study are limited due to small sample size, they justify further investigation into the fitness of these isolate types through an in vivo mouse model and genetic testing.

Disclosures

Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Honoraria|Merck: Grant/Research Support
576. Comparison of Three Blood Culture Testing Models at a Tertiary Care Hospital: Does Laboratory Centralization Work?
Authors: Haghamad Aya , Streva Vincent , Juretschko Stefan , Lemon Jamie
Published: November 2023

Background

Centralization of laboratory testing has become increasingly common in US hospital systems. One criticism of centralization is increased test turnaround time leading to potential delays in care.

Methods

In this study, we analyzed three microbiology laboratory testing models for blood cultures at a tertiary care hospital. These models were: 1) full workup in a hospital-based microbiology laboratory; 2) incubation, Gram stain (GS), and molecular blood culture identification (BCID) in a hospital-based microbiology laboratory followed by subculture identification and susceptibility testing (AST) at a centralized core laboratory; and 3) full workup in the centralized microbiology laboratory. Blood culture samples were transported 33 miles from the hospital to the core laboratory. We evaluated these three models for time from collection to positivity, time from collection to GS result, time from collection to BCID result, time from collection to organism identification, time from collection to AST, and patient length of hospital stay.

Results

We observed no statistical difference in time to blood culture positivity, time to GS result, or time to BCID result. There were shifts in the median time to AST between Model 1 (53.6h) and Model 2 (73.9h) and Model 2 and Model 3 (63.8h), but these were not statistically significant. Of note, time to AST and time to final result in Model 3 were more uniform, with fewer outliers than in the other two models. This is likely a result of the greater degree of laboratory automation in place at the core laboratory and reduced time spent in transit before culture workup. Finally, there was no difference in length of hospital stay between the hospital and decentralized models, though the hybrid approach (Model 2) resulted in increased length of hospital stay compared to either of the other models.

Conclusion

Our results suggest centralization of blood culture testing does not significantly impact timely reporting of laboratory results and has no impact on length of patient hospital stay. Interestingly, these data demonstrate potential delays when blood culture workups are split between hospital and centralized laboratories. Additional work is needed to fully understand the role of centralization of laboratory testing on treatment decisions and patient outcomes.

Disclosures

All Authors: No reported disclosures
589. Clinical Utility and Patient Characteristics Associated with Positive Whole Blood PCR for Borrelia spp. in an Endemic Area Using Novel High-Definition PCRTM assay: A Case Series
Authors: Mutti Jasmine , Moore Franklin , Paez Armando
Published: November 2023

Background

Current guidelines recommend antibody testing to detect acute borreliosis. Detectable antibody response takes about 2-3 weeks limiting its usefulness in early infection. The ChromaCode High-Definition PCR (HDPCR)™ Tick-Borne Pathogen Panel (TBP) is a research use only qualitative, real-time PCR assay for detection and identification of tick-borne pathogens including Borrelia spp. from whole blood samples.

Methods

HDPCR™ TBP was put in clinical use after this was validated in the laboratory to identify Anaplasma phagocytophilum, Babesia microti, Ehrlichia spp, Borrelia spp. (B. burgdoferi B. mayonii, and B. miyamotoi). Chart review was performed on all (+)Borrelia spp. from 8/1/22 to 12/31/22. Descriptive analysis was performed on each case. All data was captured and stored using RedCap.

Results

Over a period of 5 months, 9 (0.5%) out of 1667 tested were (+) for B. burgdorferi; one (0.06%) was (+) for B. miyamotoi; out of these 6 cases had clinical information for review as described in Table 1. Mean age was 64 years; 4 were white and 2 were Hispanic. All 6 lived in western Massachusetts, and only 1 had a known history of tick bite. All had reported systemic symptoms at the time of testing. 3 had (+) B. burgdorferi IgM antibodies;1 case tested (+) PCR for B. miyamotoi but serology was not performed. 1 case was (+) for B. burgdorferi PCR 28 days after symptom onset and had babesiosis co-infection; 1 with B. burgdorferi mono-infection had a (+) PCR test on day 14 of symptoms. All 6 had symptom improvement after doxycycline treatment for 10-14 days.

Case description

Conclusion

HDPCR™ TBP for Borrelia spp is a low yield test, even in an endemic region. All (+) cases were symptomatic and clinically improved following doxycycline treatment supporting the test’s validity. Two cases had negative IgM antibody testing and diagnosis would be likely missed without PCR testing. None were immunocompromised including 2 with prolonged PCR positivity with 1 case having babesiosis co-infection. Study was limited only to 6 cases excluding analysis of other tick-borne infections as part of syndromic testing. Clinical usefulness and timing of HDPCR™ TBP to diagnose borreliosis and other tickborne illnesses need further study.

Disclosures

All Authors: No reported disclosures
593. Evaluation of the EDTA-modified Carbapenem Inactivation Method (eCIM) with Using the EDTA Blood Collection Tube for Differentiating the Serine- and Metallo-β-lactamase (MBL) Producing Enterobacterales
Authors: Sakanashi Daisuke , Suematsu Hiroyuki , Takayama Mina , Kawamoto Yuzuka , Miyazaki Narimi , Ohno Tomoko , Yamada Atsuko , Nakamura Akiko , Ohta Hirotoshi , Koita Isao , Hirai Jun , Asai Nobuhiro , Mori Nobuaki , Mikamo Hiroshige
Published: November 2023

Background

The rapid and wide spread of carbapenemase-producing Enterobacterales (CPE) has become a global concern. Currently, β-lactams with β-lactamase inhibitors (such as ceftazidime/avibactam, relebactam/imipenem) are used for treatment of CPE infection as one of the effective agents. However, some of combinations do not have activity against MBLs. Thus, we believe that the discriminating between MBL and serine-CPE is important. The eCIM has been published by Clinical & Laboratory Standards Institute (CLSI) to differentiate to MBL from serine-CPE. The eCIM is required EDTA, that is not clinical diagnostic agent. In this study, we examined simplifying the eCIM procedure by using the EDTA blood collection tube (BCT-eCIM).

Methods

A total of 53 CPE (39 MBL and 14 Serin-CPE) were tested. The test population included 39 clinical isolates, and 14 reference strains from NCTC or ATCC (Table 1). The eCIM were performed and interpreted by following CLSI procedures. For BCT-eCIM, whole quantity of 2-mL TSB was inoculated into a BD Vacutainer EDTA Tube (2-mL) (Becton-Dickinson) (Vacutainer-eCIM) or an EDTA-2K Insepack II-D 2-mL tube (Kyokuto Pharmaceutical Industrial, Tokyo, Japan) (Insepack-eCIM); the tubes conform to International Organization for Standardization 6710, hence the 2-mL TSB inoculated tubes obtain final concentration of 4.1 to 6.8 mM EDTA. The BCT-eCIM used these tubes as a substitute for 0.5 mM EDTA TSB tube of eCIM, and any other procedures followed the eCIM procedure. Additionally, we performed the 4 mM- and 7 mM-eCIM to verify the effect of EDTA concentration (variable region of BCT-eCIM).

Table 1

Bacterial strains

Results

Table 2 and Figure 1 show the performance data of each eCIMs and the positive and negative Quality control results, respectively. The sensitivity of 4 mM-eCIM, 5 mM-eCIM, 7 mM-eCIM, Vacutainer-eCIM and Insepack-eCIM were 37/40 (93%), 36/40 (90%), 36/40 (90%), 39/40 (98%) and 39/40 (98%), respectively. The specificity of 4 mM-eCIM, 5 mM-eCIM, 7 mM-eCIM, Vacutainer-eCIM and Insepack-eCIM were 11/13 (85%), 13/13 (100%), 13/13 (100%), 12/13 (92%) and 12/13 (92%), respectively.

Table 2

Results obtained using the eCIM and BCT-eCIM

Conclusion

Our methods (BCT-eCIMs) were superior to sensitivity compared to conventional eCIMs. Therefore, BCT-eCIM may be useful in clinical settings as the simplifying method.

Disclosures

Hiroshige Mikamo, M.D, Ph.D, Asahi Kasei Pharma Corporation: Grant/Research Support|Merck Sharp & Dohme: Honoraria|Pfizer Inc.: Grant/Research Support|Pfizer R&D Japan: Honoraria|Sumitomo Pharma Co., Ltd.: Grant/Research Support|Sumitomo Pharma Co., Ltd.: Honoraria
598. Clinical Characteristics and Characterization of Hafnia Alvei Infections in Cancer Patients
Authors: Thakkar Keval , Shah Heeya , Larsen Matthew , Aslam Sadaf , Greene John
Published: November 2023

Background

There have been documented cases, although rare, of clinically significant infections caused by Hafnia alvei leading to infections such as bacteremia, pneumonia, UTI, meningitis, and empyema. H. alvei infections can be community-acquired or nosocomial. The published data for H. alvei in cancer patients is limited. The aim of this study was to characterize H. alvei infections including patient characteristics, antimicrobial susceptibility patterns, location of isolation, and microbial characteristics of isolates in cancer patients.

Methods

A retrospective cohort study was performed to review records of all consecutive patients with a positive H. alvei culture during the past 7 years. Variables included patient’s age, sex, underlying malignancy, neutrophil count, location and duration of infection, antimicrobial susceptibility patterns, hospital stay, co-isolates, and outcomes.

Results

A total of 15 patients with positive H. alvei cultures were identified at the Moffitt Cancer Center. There were 8 (53%) female and 7 (47%) male patients. The mean patient age was 65.7 ±15.8 yrs. All patients had underlying malignancies, most common type was solid organ malignancy in 11 patients (73%), and hematologic malignancies in 4 patients (27%). Two patients (13%) were neutropenic at the time of positive culture. H. alvei isolates were first identified in patients at a median of 8 days and an average of 11 days after admission to the hospital. Of the 15 isolates, 8 (53%) were monomicrobial and 7 (47%) were polymicrobial cultures (Table 1). Co-isolates and susceptibilities are shown in the Table 2 and 3.

Table 1

Demographic data for all identified patients

Table 2

Characteristics of H. alvei isolations

Table 3

H. alvei antibiotic susceptibility report

Conclusion

This study demonstrated that H. alvei is a truly rare pathogenic organism with only 15 documented cases of isolation over an 80-month time period at an academic cancer center. In patients with underlying malignancies, the organism tends to have a predilection for both the urinary tract and abdominal wounds, and can be isolated from pure cultures in the urine and with co-isolates in all other locations. Our study showed that resistance with H. alvei is usually with ampicillin and most of our isolates were resistant to cefazolin and cefoxitin. When infection does occur, isolates tend to be susceptible to standard antibiotics such as aminoglycosides and ciprofloxacin.

Disclosures

All Authors: No reported disclosures
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

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

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

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 > 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

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 >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 >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 >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

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 =/ > 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

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

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

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

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
686. Management and Outcomes of Patients Referred to a Specialty Clinic for C. difficile Infection
Authors: Hunt Aaron , Danziger Larry H , Johnson Stuart , Skinner Andrew M
Published: November 2023

Background

Clostridioides difficile infection (CDI) poses an urgent threat in the United States with an estimated 223,900 cases of hospitalization and 12,800 estimated deaths in 2017. CDI manifestations range from diarrhea, pseudomembranous colitis, to fulminant colitis. Due to spores that are unaffected by current antimicrobial therapies, recurrence remains a common challenge. Patients with 2 or more episodes have an estimated 40-65% rate of recurrence. We reviewed the management and outcomes of patients referred to our specialty CDI clinic.

Methods

A retrospective chart review was conducted on all new patients presenting to the Loyola University Medical Center CDI clinic between 01/01/2021 and 12/31/2021. Each chart was reviewed for demographic information, comorbidities that may confound diagnosis, and characteristics that place the patient at high risk of recurrent CDI. Visits were characterized by the number of prior CDI episodes, timeline of recurrences, and prior therapies used. 30- and 60-day symptom recurrence were assessed.

Results

A total of 48 new patients presented to the CDI clinic. The median age was 63 years, 64.5% were white, and 64.5% were female. Patients presenting with recurrent CDI accounted for 79% of cases (38/48), with 48% (13/48) of patients having two or more recurrences. The most common decision for initial management was to not give further antimicrobials and monitor for symptoms (35%). 12% of patients only required monitoring while 23% of patients had a questionable CDI diagnosis and were referred elsewhere for further evaluation. For the 30 patients who received treatment, vancomycin or fidaxomicin tapers were selected 73% (22/30) and bezlotoxumab 20% (6/30) of the time. 8.6% (2/23) of patients with a history of two or more CD episodes had recurrence. Overall, patients experienced a subsequent recurrence rate of 12.5% (6/48) and 15% (7/48) at 30 and 60 days, respectively.

The number of times each management approach was selected for initial patient appointments.

The number of times each treatment regimen was selected when a patient was deemed to need antibiotic therapy.

The percentage of patients who had either recurrence or resolution at 60 days after the end of therapy.

Conclusion

CDI is a difficult-to-treat infection with many patients suffering from multiple recurrences. Dedicated outpatient follow-up is important for monitoring therapy and excluding alternate etiologies. Expert management of CDI through a dedicated clinic results in lower recurrence for high-risk patients and spared 35% of patients further antimicrobial exposure.

Disclosures

Larry H. Danziger, PharmD, Ferring Pharmacetuicals: Advisor/Consultant Andrew M. Skinner, MD, Academy for Continued Healthcare Learning: Honoraria|American Society of Healthcare Pharmacists: Honoraria|Ferring Pharmaceuticals: Honoraria|MJH Life Sciences: Honoraria
688. Risk of Clostridioides difficile Infection and Antibiotic Associated Diarrhea in Patients Receiving Outpatient Parenteral Antimicrobial Therapy
Authors: Jaramillo Mario , Musmar Ahmad S , Shi Aishan , Al Momani Shaden , Alexander Perry D , Zangeneh Tirdad
Published: November 2023

Background

The colonic microbiome plays a critical role in resisting the ingrowth of pathogenic microbes like Clostridioides difficile (C. difficile). Disruption of the microbiome by antibiotics is known to cause antibiotic-associated diarrhea (AAD) and C. difficile infection (CDI). Outpatient parenteral antimicrobial therapy (OPAT) reduces hospital length of stay and exposure to healthcare-associated pathogens which may decrease the incidence of CDI. Previous studies that compared patients who received metronidazole for non-CDI indications with those who did not found a reduction in CDI among patients who received metronidazole. The aim was to study the incidence of AAD and CDI in the OPAT patient population and compare the incidence rate between patients who received oral metronidazole for non-CDI indications with those who did not.

Methods

We retrospectively reviewed a cohort from our facility's OPAT program. We included adult patients (18 years or older) discharged to home or skilled nursing facility (SNF) on OPAT over a 2-year time span, regardless of diagnosis. Pregnant patients, patients with active CDI before starting OPAT, and those who were receiving an associated CDI treatment were excluded. Antibiotic-associated diarrhea was defined as 3 or more loose or watery stools per day with negative CDI testing or spontaneous improvement after stopping antibiotics. Community-onset and healthcare facility–associated CDI (CO-HCFA CDI) was defined as 3 or more watery stools per day with a positive stool C. difficile diagnostic test in the community or within the first 3 days of readmission, provided the diagnosis was made less than 4 weeks since discharge from a healthcare facility.

Demographics of Patients Discharged on OPAT.

Patients selected between June 1, 2018 and June 2020, grouped by whether or not they developed Clostridioides difficile infection (CDI). SD= standard deviation; Q1= 1st quartile; Q3= 3rd quartile.

Results

Of the 617 charts that met inclusion criteria, 31 had AAD and 3 had CO-HCFA CDI. Incidence of CO-HCFA CDI was < 1%; < 1 per 1000 person-day and incidence of AAD was 5.02%. The protective role of metronidazole could not be studied due to the rarity of CDI in this study.

Patients with positive CDI after initiation of OPAT and associated characteristics.

Conclusion

Although our study was not able to answer our initial question when comparing the effect of metronidazole within OPAT groups and rates of CDI, our data is promising for showing low rates of CDI in patients receiving OPAT. This study demonstrates the putative benefits of OPAT with reduced CDI incidence regardless of use of anti-CDI drugs.

Disclosures

Tirdad Zangeneh, DO, AiCuris: Grant/Research Support
689. Significant Improvement in Hand Hygiene Compliance and Decline in Clostridioides difficile Infections with Implementation of Infection Prevention Interventions
Authors: Kaushik Ashlesha , Beal Kristen , Gupta Sandeep
Published: November 2023

Background

Per CDC, C. difficile is an urgent microbial threat. Despite use of CDC diagnostic criteria, 2-step testing protocol and antimicrobial stewardship interventions limiting broad spectrum antimicrobial use, we witnessed an increase in infections in 2022, therefore, additional interventions were implemented.

Methods

A multifaceted QI intervention program to improve IPC (infection prevention and control) practices was implemented in July 2022 at a 160-bed tertiary care center serving the tristate area of Iowa, South Dakota and Nebraska. Interventions included: auditing and real time observations for health care personnel (HCP) hand hygiene compliance; monitoring soap/sanitizer usage; educational interventions including posters posted throughout the hospital emphasizing hand hygiene, “A clean in and clean out” approach and contact precautions reminders posted in patient rooms/nursing stations, weekly nursing huddles focused on nursing and ancillary staff education, provider counseling and continued coaching. Pre-intervention period (P1: 1/10/2021- 6/30/2022) was compared with Intervention period (P2: 07/01/2022-3/31/2023) for hand hygiene compliance and C. difficile infection rates.

Results

Overall adequate hand hygiene compliance rates for all health care personnel (HCP) increased from 71% during P1 to 85% during P2 (P< 0.05). All categories of HCP showed a significant improvement in hand hygiene compliance from P1 to P2, with rates for physicians increasing from 74% to 92% (p< 0.05), nurses from 68% to 94% (p< 0.001); nurse practitioners/physician assistants from 75% to 90% (p< 0.05), ancillary staff (chaplain, medical technicians, social workers) from 60% to 89% (p< 0.01)]. Hand hygiene product use increased significantly and soap usage alone increased from 45% to 75% in P2 (p< 0.05). C. difficile infections declined significantly from a mean of 1.9 infections per 1000 patient days during P1 to 0.5 infections per 1000 patient days during P2 (p< 0.001); SIR (Standardized infection ratio) decreased from 1.14 during P1 to 0.4 during P2 (p< 0.01). No C. difficile related mortality was observed.

Conclusion

With implementation of multifaceted IPC interventions, significantly improved hand hygiene rates and a significant decline in C. difficile infections were observed.

Disclosures

All Authors: No reported disclosures