bluuebunny/crossref_metadata_2025 huggingface dataset:
310. Longitudinal Assessment of Point-of-Care LumiraDx Antigen and Antibody Test Performance During Acute SARS-CoV-2 Infection and Recovery
Authors: Dalmat Ronit , Prabhu Roshni , Bauer Marie , Ikuma Matthew H , Hamilton Daphne , Rechkina Elena A , Cantera Jason L , Grant Benjamin D , Drain Paul K
Published: December 2022

Background

Rapid COVID-19 tests can offer significant advantages and reduce health disparities. The LumiraDx SARS-CoV-2 platform can perform microfluidic fluorescence assays for the rapid detection of SARS-CoV-2 antigen (Ag) and antibodies (Ab). We evaluated both tests in a longitudinal cohort to evaluate performance during acute SARS-CoV-2 infection and recovery.

Methods

We collected nasal samples from 71 unique participants at four clinic visits spanning 0-21 days since symptom onset (DSSO); blood samples were collected from the same participants over six visits spanning 0-87 DSSO. For Ag testing, 232 anterior nasal swabs were assayed by: 1) the LumiraDx Ag test, 2) a laboratory-based electrochemiluminescence immunoassay for N Ag, 3) RT-PCR (Hologic Panther Fusion), and 4) culture (growth in VeroE6AT cells). For Ab testing, 308 serum samples were assayed by: 1) the LumiraDx Ab test and 2) Roche Elecsys Anti-S SARS-CoV-2 total Ab test. Measures of concordance [positive predictive agreement (PPA), negative predictive agreement (NPA), and Cohen’s Kappa (Κ)] were estimated for qualitative results of the LumiraDx tests versus corresponding lab reference tests. Confidence intervals were estimated via bootstrapping.

Results

LumiraDx Ag results had strong agreement with lab N-Ag results (Κ > 0.80) across all samples. Between 0-5 days, agreement was perfect, except for one sample resulting positive by LumiraDx Ag and negative by lab Ag. Agreement with PCR results was moderate overall (Κ=0.60), though substantial (Κ > 0.6) for both 0-5 DSSO (PPA=0.96/NPA=0.80) and 6-10 DSSO (PPA=0.96/NPA=0.59). Agreement with culture results was moderate overall (Κ=0.46): substantial (Κ=0.6) between 0-5 DSSO (PPA=0.96/NPA=0.60) and fair (Κ=0.29) between 6-10 DSSO (PPA=1.0/NPA=0.32).

LumiraDx Ab results showed almost perfect agreement with lab Ab results across all samples (Κ=0.88), with substantial agreement (Κ > 0.7) for samples collected 0-10 DSSO (PPA=0.93/NPA=0.89) and 11-28 DSSO (PPA=0.99/NPA=0.69).

Longitudinal agreement of LumiraDx antigen test result and culture positivity, by PCR Ct value.

Nasal samples grouped by participant (lines) and agreement of results between LumiraDx antigen test result and culture positivity (proxy for infectiousness).

Conclusion

LumiraDx rapid tests perform well compared to more costly and time-consuming lab methods of Ag and Ab detection. The rapid Ag test may be helpful in identifying patients infectious between 0-5 DSSO, given the substantial concordance of the rapid Ag test and culture positivity.

Disclosures

Daphne Hamilton, BA, Roche (spouse is employed by Roche): Employee.
315. Standardized Measurement of SARS-CoV-2 Viral Load Over Time in Respiratory Compartments and in Response to Remdesivir Treatment
Authors: Beckwith Curt , Sam Soya , Novitsky Vladimir , Shin Jimin , Lethbridge Kevin , Steingrimsson Jon , Sahu Sujata , Rapoza Kim , Chandran Karen , Mariano Vincent J , Bazerman Lauri , Hipolito Evelyn R , Diaz Isabella , Carnevale Daniella M , Gillani Fizza S , Caliendo Angela , Kantor Rami
Published: December 2022

Background

Two years into the pandemic, clinicians do not have access to a standardized measurement of SARS-CoV-2 viral load (VL) that allows for VL comparison across clinical specimens and different assays. Reliable VL measurement in diverse respiratory specimens, over time, and in response to treatments such as remdesivir (RDV), could better inform treatment and prevention.

Methods

To investigate the use of a standardized VL assay in respiratory specimens, we enrolled patients hospitalized with COVID-19 in Providence, RI, with/without RDV exposure; collected serial samples from 4 compartments (nasopharyngeal-NP, nasal-NA, oropharyngeal-OP, saliva-SA) in 3 visits during the 1st week of hospitalization; and characterized SARS-CoV-2 VL using a ChromaCode HDPCR™ quantitative research use only assay, calibrated to the first World Health Organization (WHO) International Standard (IS). Linear mixed effects models and associated regression coefficients were used to analyze inter-compartmental VL differences at enrollment, over time, and with/without RDV.

Results

Of 35 participants (60% male; 70% White, 14% Hispanic/Latino, 49% RDV exposure), all had visit 1 samples (median hospital day 1, IQR 0-2; pre-RDV for those exposed); 80% visit 2 samples (median hospital day 2, IQR 1-8); and 37% visit 3 samples (median hospital day 4, IQR 3-7). Overall, 38 NP, 67 NA, 57 OP, and 67 SA samples were collected. Mean log VLs (Log10IU/mL) differed by compartment at visit 1 (NP 6.3, NA 4.9, OP 4.1, SA 5.6, p=0.0001) and significantly decreased over time in all compartments (p< 0.04 for all comparisons). Log VL change over time was not significantly different between compartments or between people treated/not treated with RDV.

Conclusion

We successfully measured respiratory intercompartmental SARS-CoV-2 VL differences among hospitalized patients using a standardized assay calibrated to the WHO IS. Dissemination of standardized VL measurement methods will allow accurate VL comparisons across assay types quantified in IU/mL and improve assessment of the impact of COVID-19 treatments. Inter-compartmental VL differences at baseline may indicate sampling variability or different viral burden. RDV did not appear to accelerate viral decay.

Disclosures

Curt Beckwith, MD, Gilead Sciences, Inc: Grant/Research Support Jon Steingrimsson, PhD, Gilead: Grant/Research Support Angela Caliendo, MD, PhD, ChromaCode: Advisor/Consultant|Danaher/Cepheid: Advisor/Consultant|First Light: Advisor/Consultant|Hologic: Grant/Research Support|ID Connect: Advisor/Consultant|Quidel: Advisor/Consultant|Visby: Advisor/Consultant Rami Kantor, MD, Gilead Sciences: Grant/Research Support.
320. Clinical Impact of Metagenomic Next Generation Sequencing in a Large Pediatric and Adult Cohort
Authors: Lehman Alice , Goren Lea , Toles Olivia , Andrews Shannon L , Thielen Beth K , Drozdov Daniel , Rubin Nathan
Published: December 2022

Background

Plasma metagenomic next-generation sequencing (mNGS) is an emerging diagnostic tool. As the clinical use of mNGS increases, efforts to better understand the role of mNGS in diagnosis and management of infectious diseases are essential. Current literature is limited to small retrospective reviewers and a prospective study therefore subject to institutional variability. Here, we aim to describe the use, sensitivity, time to diagnosis, clinical impact, and cost effectiveness of mNGS in the largest patient cohort to date.

Methods

We included pediatric and adult patients who had plasma mNGS testing as part of care from December 2017 through December 2021 at University of Minnesota (UMN). Patients were identified using the Karius database. Electronic medical records were reviewed for every mNGS test, recording patient demographics, underlying conditions, indications, and results within 30 days of mNGS. All cases were assessed by 2 reviewers including one board-certified infectious diseases doctor. Sensitivity of mNGS was determined relative to conventional tests. The primary end point was change in clinical management. Secondary end points included accuracy, time to diagnosis, and infectious disease consultation. UMN IRB approved this study as non human subjects research.

Results

584 mNGS tests were ordered in the study period, with 203 reviews completed to date. Solid organ transplantation (SOT) (32%) was the most common underlying condition, followed by hemopoietic stem cell transplantation (HSCT) (28%). Fever (45.8%), then pulmonary findings (26%) were the most common indications for ordering mNGS. Conventional and mNGS tests identified an infectious cause of the clinical syndrome in 49% of cases, while a contaminant was found in 52% of cases. The sensitivity of mNGS in identification of infectious cause was 47%, approximately 7% more sensitive than conventional testing. Despite this increased sensitivity, mNGS changed clinical management in 20% of cases.

Conclusion

mNGS demonstrated superiority in accurate detection of infectious causes of clinical syndromes, however, changed clinical management in a minority of cases, suggesting timing of the mNGS test is critical. This study identified SOT and HSCT as high yield patient groups for implementation of a prospective study.

Disclosures

Beth K. Thielen, MD, PhD, Horizon: Advisor/Consultant|Horizon: Honoraria|Merck: Grant/Research Support.
334. Clinical Outcomes with Implementation of Accelerate Pheno Blood Culture Detection System for Gram Negative Bacteremia
Authors: Lee Shu Xian , Wu Benita Y , Suter Kurt , Lokant Matthew S , Ward Andrew , Spigelmyer Amy E , Freeman Lauren K , Thompson Jesse M , Demkowicz Ryan , Howard Catessa A , LaSala Rocco , Reece Rebecca
Published: December 2022

Background

Bacteremia is a life-threatening illness. Delayed treatment increases patient morbidity and healthcare costs. Accelerate Pheno™ Blood Culture Detection System (AXDX) is a novel diagnostic technology for rapid detection of gram-negative bacteremia. Studies have shown accurate and faster time to speciation and sensitivity (TTSS) by AXDX compared to conventional modality. Our unique study examined the direct impact of AXDX on clinical outcomes and cost.

Methods

This retrospective study consisted of 213 patients aged 18 years and older admitted to our academic institution with gram-negative bacteremia. The pre-AXDX group had 109 patients admitted in 2019 and the post-AXDX group had 104 patients admitted in 2021. Demographics, microbes, TTSS, time to de-escalation of therapy (TTDeT), length of stay (LOS), readmissions, mortality rates, and Clostridioides difficile infection (CDI) rates were recorded.

Results

The pre-AXDX group had 51.4% females, mean age of 60.3 years, mean Charlson Comorbidity Index (CCMI) of 2.2, mean LOS of 21.2 days, and mean Pitt Bacteremia Score (PBS) of 2.4. The post-AXDX group had 52.0% females, mean age of 63.7 years, mean CCMI of 3.0, mean LOS of 15.0 days, and mean PBS of 2.7. Both groups’ top 2 sources of bacteremia were urinary and gastrointestinal and top 2 microbes were Escherichia coli and Klebsiella pneumoniae. Pre-AXDX's mean TTSS was 71.9 hours and 23.6 hours for post-AXDX. Pre-AXDX's mean TTDeT was 74.0 hours and 43.9 hours for post-AXDX. The pre-AXDX cohort had 7.4% more related readmissions, 5.5% more CDI, and 0.3% more inpatient mortality than post-AXDX group.

Conclusion

In addition to faster TTSS with AXDX as seen with previous studies, our study shows clinical advantages with AXDX use. Both groups were comparable in bacteremia sources and microbes. The post-AXDX group had higher CCMI and PBS scores, indicating they were more ill. Despite this, the pre-AXDX group had 30.05 hours longer TTDeT, 6.17 days longer mean LOS, 5.45% more CDI, 7.12% more readmissions, and 0.26% higher mortality. The pre-AXDX group also reported adverse reactions to antibiotics, while post-AXDX did not. Our data shows AXDX use improves clinical outcomes with reduced adverse effects, mortality and CDI rate and lower costs with less LOS and readmission rates.

Disclosures

All Authors: No reported disclosures.
339. Feasibility of Heteroresistance Screening on Escherichia coli (EC) to Predict the Presence of Inner Colonies (IC) During Fosfomycin Disk Diffusion (DD) Testing
Authors: Salay Jenna , Bixby Morgan L , Hirsch Elizabeth B
Published: December 2022

Background

Growth of IC within the zone of inhibition during fosfomycin DD testing in EC are found, but CLSI and EUCAST interpretation criteria for IC are contradictory. There is a need to determine appropriate methods of interpretation to prevent resistant infections, thus evaluating the susceptibility of IC EC isolates in comparison to parent can help determine optimal methods for DD testing. A heteroresistance screening test has potential to identify isolates with IC. We sought to determine the feasibility of heteroresistance screening to predict the presence of IC in clinical EC isolates.

Methods

A convenience collection (n=48) of EC parent isolates underwent fosfomycin DD testing to identify those with IC. Broth microdilution (BMD) testing was performed on all parent and IC (n=34) to determine minimal inhibitory concentrations (MICs) to establish inclusion criteria for heteroresistance screening. A disk elution test for heteroresistance screening was performed in duplicate on separate days. In tubes of Mueller-Hinton broth, 6 commercial fosfomycin disks (each 200 μg fosfomycin and 50 μg glucose-6-phosphate) were eluted for 90 minutes. One hundred microliters of each bacterial isolate from an overnight culture was suspended in tubes. A positive test was a turbid tube after 72 hours of incubation.

Results

The parent isolates (n=48) had an MIC range of 1 to >256 μg/mL with a median of 4 μg/mL. The subset of IC isolates (n=34) had an MIC range between ≤8 and >1024 with a median of 128 μg/mL. Nineteen IC isolates met the inclusion criteria for the heteroresistance screening; 5 isolates did not produce IC (MIC range of 1-32 μg/mL) while 14 isolates produced IC (MIC range of 1-16 μg/mL). Of these 19 isolates, 6 (32%) were heteroresistant using the disk elution test. Of those with IC, 4 (29%) were heteroresistant while 2 (40%) isolates without IC were heteroresistant.

Conclusion

A heteroresistance screening test did not provide consistent data to predict the presence of IC among this EC collection. A larger isolate set and further studies are needed to understand the feasibility of a heteroresistance screening test and increased resistance in IC resulting from fosfomycin DD testing among EC.

Disclosures

Elizabeth B. Hirsch, PharmD, FCCP, FIDSA, Melinta: Advisor/Consultant|MeMed: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support.
347. Azole Activity against Filamentous Fungi Causing Invasive Infections in Patients from ICU and Non-ICU Units (2017-2021)
Authors: Carvalhaes Cecilia G , Rhomberg Paul , Rhomberg Paul , Schaefer Beth A , Pfaller Michael A , Castanheira Mariana
Published: December 2022

Background

Invasive fungal infection (IFI) is associated with high mortality rates in critically ill patients. Appropriate antifungal treatment is crucial for managing IFI. We evaluated the in vitro activity of isavuconazole (ISC), itraconazole (ITC), posaconazole (PSC), and voriconazole (VRC) against contemporary moulds from ICU and non-ICU patients.

Methods

1,226 moulds causing IFI (386/840 from ICU/non-ICU patients, respectively) were consecutively collected (1/patient) in 43 worldwide hospitals from 2017-2021 and susceptibility tested by CLSI broth microdilution. CLSI interpretation criteria were applied. Pneumonia was the predominant infection type among ICU (81.6%) and non-ICU (71.8%) patients.

Results

Aspergillus spp. was the most common mould (87.6%/80.5%). A. fumigatus (AFM; 76.0%/65.4% of Aspergillus), A. section Flavi (ASF; 9.2%/10.9%), and A. section Nigri (ASN; 7.4%/13.6%) were the top 3 Aspergillus groups. ISC inhibited 94.2%/91.2%, 100.0%/98.6%, and 96.0%/96.7% of AFM, ASF, and ASN from ICU/non-ICU, respectively, at the epidemiological cut-off values. Similar activities were noted for ISC, PSC, ITC, and VRC against AFM from ICU (MIC50/90 range, 0.25-1/0.5-1 mg/L) and non-ICU (MIC50/90 range, 0.5-1/0.5-2 mg/L) isolates. No difference in the azole activities was noted against ASF from ICU (MIC50/90 range, 0.5/0.5-1 mg/L) and non-ICU (MIC50/90, 0.5/0.5-1 mg/L) or ASN from ICU (MIC50/90 range, 0.5-2/1-4 mg/L) and non-ICU (MIC50/90 range, 0.5-2/1-4 mg/L) isolates. VRC-non-susceptible (NS) AFM isolates were detected in 9.3% of ICU and 9.0% of non-ICU isolates. Among VRC-NS AFM from ICU/non-ICU, 58.3%/27.5% were wildtype (WT) to ISC, 50.0%/25.0% were ITC-WT, and 75.0%/50.0% remained VRC-WT, respectively. VRC was the most active azole against Scedosporium spp. (SCE) but was less active against Mucorales (MUC) than the other azoles. All azoles showed limited activity against Fusarium spp. (FUS). No difference on azole activities against SCE, MUC, and FUS were noted from ICU and non-ICU isolates.

Conclusion

ISC was active against Aspergillus isolates from ICU and non-ICU, including against VRC-NS AFM from ICU. Azoles displayed similar activity against moulds from ICU and non-ICU units.

Disclosures

Cecilia G. Carvalhaes, MD, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Paul Rhomberg, BS, MT(ASCP), Cidara: Grant/Research Support|Pfizer: Grant/Research Support Beth A. Schaefer, BA, MT(ASCP), Pfizer: Grant/Research Support Michael A. Pfaller, MD, Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Cidara: Grant/Research Support|GSK: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support.
352. Evaluation of Serial Serum (1-- >3)-b-D-glucan Assay in Patients with Invasive candidiasis, Pneumocystis Jiroveci Pneumonia and Aspergillosis
Authors: Cari Evelyn Villacorta , Siddiqui Zubair , Leedy Nicole , Fenwick Alexander , Myint Thein
Published: December 2022

Background

Serum (1-- >3)-b-D-glucan (BDG) assay is a noninvasive serological marker that can be used as an adjunct to the diagnosis of invasive candida infections, Pneumocystis jiroveci pneumonia (PJP) as well as aspergillosis. There is limited data in serial monitoring of serum BDG in those fungal infections after treatment was initiated. Figure 1:Serial serum BDG levels of each subject after treatment initiation

Methods

This is a cross-sectional study of subjects with proven fungal infection (invasive candidiasis, aspergillosis or PJP) and with increased serum BDG >500 pg/ml who were admitted to University of Kentucky (UK) hospitals or clinics from 01/2012 to 01/2021. It was approved by institutional IRB. We compared at least two measures of the serum β-D-glucan levels obtained within two to eight weeks after initial diagnosis to evaluate the levels of β-D-glucan during and post-treatment. A decrease in BDG level is defined as any value below 500 pg/ml; normal serum BDG level as < 80 pg/ml.

Results

Of 26 subjects included in this cohort, 14 (51.8%) subjects had invasive candidiasis, six (22.2%) subjects had PJP, and six (22.2%) subjects had invasive aspergillosis. Twelve patients did not have a repeat BDG level after at least two separate levels with >500 pg/ml. Ten (38.5%) subjects had a decline in BDG level 2-3 weeks after starting treatment. Serum BDG level did not return to within normal limits at week 4 of treatment except one patient.

A repeat serum BDG level was seen decline at three weeks of treatment in four of six (66.6%) subjects with PJP, six weeks of treatment in three of six (50.0%) subjects with invasive aspergillosis and 8 weeks of treatment in six of 14 (42.8%) patients with invasive candidiasis. Two subjects had persistent elevation of BDG 8 weeks after treatment. (Figure 1)

Conclusion

Serial serum BDG level was not routinely done for monitoring the treatment response in this cohort. There was no linear decline in serum BDG level even after appropriate treatment in invasive fungal infections. A decline in serum BDG level was best observed among subjects with PJP pneumonia. It appears that the duration of a decline in serum BDG level was shorter in patients with PJP and longer in patients with invasive candidiasis.

Disclosures

All Authors: No reported disclosures.
358. Surveillance of Activity of Antifungals: Data from the Analysis of Resistance in Antifungals (ARIA) 2020 Study
Authors: Hawser Stephen , Kothari Nimmi , Lemos Bárbara
Published: December 2022

Background

ARIA is a new annual global surveillance initiative collecting yeast and fungal isolates from worldwide designed to determine resistance to antifungal agents and trends over time. The ARIA program was developed in 2020 to provide a repository of recent clinical fungal isolates with known susceptibility profiles and to monitor resistance trends over time. ARIA reports the susceptibility patterns of its earliest data concerning echinocandins, second-generation triazoles, and fluconazole against clinical Candida albicans, non-albicans strains including C. auris, Aspergillus and Fusarium isolates from worldwide sources.

Methods

Isolates were collected from hospital worldwide during 2020, shipped to a central laboratory and re-identified by MALDI-TOF or molecular methods. MIC tests were performed by broth microdilution method in line with CLSI susceptibility testing standards. Percentage of susceptibility was calculated according to CLSI breakpoints. Antifungals tested were amphotericin B (AMB), anidulafungin (ANID), fluconazole (FLU), isavuconazole (ISA), micafungin (MIC), posaconazole (POS), and voriconazole (VOR). All testing was performed according to CLSI M27-A4 and M38-A2 methodologies.

Results

See table.

Conclusion

Ongoing antifungal resistance surveillance like the ARIA program is of utmost importance in order to monitor the efficacy of traditional empirical therapy and for the development of novel antifungal agents. This repository and ongoing ARIA program will provide a resource to better support the biopharmaceutical industry’s goals to develop new and more potent antifungal agents.

Disclosures

All Authors: No reported disclosures.
364. Diagnosis of Amebic Liver Abscess by a Commercial Multiplex Stool Amplification Assay. A Potentially Useful Alternative in Limited-Resources Settings.
Authors: Murillo Jorge , Torres Jaime , Baquero Julio , Leal Vanessa , Jimenez Ana , Martinez Elena , Garcia Chloris
Published: December 2022

Background

Amoebic liver abscess (ALA) is caused by the protozoan parasite Entamoeba histolytica. Clinical and radiological features of ALA often mimic those of pyogenic liver abscess (PLA). Currently, differential diagnosis between ALA and PLA relys on microscopic examination, anti-amoebic IgG serology, and culture of aspirate for pyogenic organisms. Therefore, there is a need for new, rapid and more accurate microbiological methods for diagnosing ALA. Unfortunately, with few exceptions, available reports involved the use of inhouse or laboratory-tailored polymerase chain reaction (PCR) assays.

We herein report our recent experience with the successful use of a commercial multiplex, nested PCR assay designed for stool, in the diagnosis of two cases of ALA.

Methods

Two severely ill adult Latin American migrants presented with fever, malaise, non-bloody diarrhea, abdominal pain and leukocytosis. CT scans revealed single large hypodense, inflammatory, liver cystic lesions.

Results

Necrotic material obtained by needle aspiration under guidance and stool samples were processed by FilmArray Gastrointestinal Panel (BioFire Diagnostics, Salt Lake City), designed to detect 13 bacterial, 5 viral and 4 parasitic pathogens, both amplified only for E. hystolitica DNA. ELISA serology for amoeba was also positive. Bacterial cultures were sterile. Treatment with Metronidazole and paromomycin resulted in complete recovery.

Conclusion

Analysis of liver abscess content using a commercially available, multiplex, nested PCR assay designed for stool, may represent a convenient alternative to currently available diagnostic methods, providing rapid results and allowing for immediate choosing of specific therapy targeting single pathogens on more rational basis.

Since there are several commercially available multiplex PCR panels containing primers for E. histolytica, their use for evaluation of liver abscess samples has some theoretical advantages for the diagnosis of ALA, such as simplicity, ample availability, rapid processing time and capacity to exclude simultaneously several potential pathogens. Nevertheless, further testing is necessary to validate their use in liver abscess diagnosis and define their false positivity and negativity rates.

Disclosures

All Authors: No reported disclosures.
365. Hospitalizations Associated with Strongyloidiasis in the United States, 2003-2018
Authors: Inagaki Kengo , Bradbury Richard S , Hobbs Charlotte V
Published: December 2022

Background

Strongyloides stercoralis is considered to be historically endemic in Appalachia and the American South, but recent surveillance data, especially data evaluating strongyloidiasis associated with hospitalization, are lacking in most parts of the US.

Methods

We performed a population-based retrospective analysis on strongyloidiasis using the National Inpatient Sample from 2003-2018. Geographic distribution of strongyloidiasis associated hospitalization was assessed. Logistic regression was used to identify risk factors associated with strongyloidiasis.

Results

We identified 6931 hospitalizations associated with strongyloidiasis during the study period (11.8 per million hospitalizations). The rate of strongyloidiasis was highest in the US Northeast region including the Middle Atlantic division (47.1 cases per million population, adjusted odds ratio, aOR: 2.00 [95% confidence interval, CI: 1.58-2.53]), and the East South Central division (27.5 cases per million population, adjusted odds ratio, aOR: 2.77 [95% confidence interval, CI: 2.02-3.80]) (Figure 1, Figure 2). Older age, male sex, non-white race/ethnicity particularly Hispanic and Asian, non-private insurance, and residence in neighborhoods with low median income were also associated with strongyloidiasis (Table, Figure 2). Immunocompromising conditions, particularly human immunodeficiency virus infection, were present in 41.3% of hospitalizations with strongyloidiasis (Table). In-hospital death was seen in 7.8% of cases with strongyloidiasis-associated hospitalization.

Conclusion

Strongyloidiasis-associated hospitalization is rare in the U.S. but can be associated with mortality. It occurs more frequently in poor and marginalized populations. Immunocompromised conditions were common among hospitalized patients with strongyloidiasis. Enhanced surveillance efforts are needed to inform health policies for improving the health of at-risk populations.

Disclosures

Charlotte V. Hobbs, MD, Biofire (Biomerieux): Advisor/Consultant.
366. Optimization of a Surrogate Assay for Efficacy of a Malaria Transmission Blocking Vaccine
Authors: Meehan Cristina , Meehan Cristina , Duffy Patrick , Renn Jonathan , Zaidi Irfan
Published: December 2022

Background

An estimated 241 million malaria cases and 627,000 malaria deaths occurred worldwide in 2020. Efforts to develop a higher efficacy malaria vaccine are a global priority, but parasites pose a complex biological puzzle for vaccine development. Innovative vaccine strategies include transmission blocking vaccines (TBV) that target the mosquito stages of parasite development to interrupt parasite transmission. The current leading TBV called Pfs230D1-EPA targets Pfs230, a Plasmodium falciparum gamete surface protein that mediates binding of microgametes to red blood cells. Antibodies against Pfs230 bind and lyse gametes in a complement-dependent manner to block transmission.

Methods

Here, we are exploiting a panel of human monoclonal antibodies (hmAb) generated from human volunteers who received Pfs230D1-EPA formulated in Alhydrogel or AS01 adjuvants, to develop a competitive ELISA platform. This assay will quantify epitope-specific serum antibodies along with their features and effector functions, expanding the conventionally used functional assay of standard membrane feeding (SMFA).

Results

The competitive ELISA is being developed with single-chain variable fragments (ScFv) to define epitope-specific binding of antibodies in sera from vaccinated individuals. Sera of human volunteers from trials in Mali, Africa will be assayed to assess epitope-specific serum antibody binding that is competed off in the presence of saturating levels of ScFv. Preliminary optimization of the competitive assay has shown concentration-dependent epitope-specific competition between ScFv and hmAbs and confirmation of ScFv binding to Pfs230D1 antigen.

Conclusion

Further optimization of this assay will characterize the complement-binding and isotype/subclass-specific features of epitope-specific antibodies. These efforts will lay the foundations for standardized assays that can assess correlates of vaccine efficacy and durability of this leading TBV.

Disclosures

All Authors: No reported disclosures.
370. Toxoplasma gondii IgG Seropositivity is Associated with Increased Schizophrenia, Hospitalization, and 1-year Mortality— a Multicenter Research Network Study
Authors: Montalbano Gabrielle E , Reno Elaine , Rossetto Marika , Zhang Alexander , Kung Vanessa , Franco-Paredes Carlos , Vargas Barahona Lilian , Chastain Daniel B , Montoya Jose G , Henao-Martínez Andrés F
Published: December 2022

Background

Despite Toxoplasma seropositivity found in about one-third of the global population, we lack information about the clinical outcomes of patients with past exposure to this parasite without the manifested disease. We aim to evaluate 1-year mortality and mental health diagnosis in patients with Toxoplasma IgG seropositivity.

Methods

We queried a federated national multicenter network to validate mortality risk differences between Toxoplasma IgG seropositive and seronegative patients from 2010 to 2021, excluding patients with active disease. We used propensity score matching to assess independent mental health outcomes and mortality risk 1-year after serology.

Results

We found 6244 patients with Toxoplasma IgG positivity without toxoplasmosis and 29,179 patients with negative Toxoplasma IgG. Patients with positive Toxoplasma IgG were slightly older (46.1 ± 17 vs. 45±16.5, p< 0.0001) and more likely to be Hispanic (15% vs. 12%, p< 0.0001). Toxoplasma gondii IgG seropositivity was more often present in patients with neoplasms (25% vs 22%, < 0.0001), type 2 diabetes mellitus (13% vs 12%, p=0.0284), and less likely in transplant recipients (7% vs. 8%, p=0.0015), and liver cirrhosis (5% vs 7%, p. < 0.0001). Propensity score matching to 6099 seronegative patients adjusted for age, gender, race, ethnicity, heart disease, transplant, neoplasm, and cirrhosis found that seropositive patients had an increased risk of 1-year mortality (OR: 1.2, CI: 1.06-1.4, p=0.0036) (Figure 1), hospitalization (OR:1.2, CI: 1.1-1.3, p< 0.0001) and schizophrenia (OR: 1.4, CI: 1.01-1.8, p=0.04). An increased risk was not seen with bipolar disorder (OR: 0.86, CI: 0.66-1.15, p=0.3206). Figure 1.Kaplan-Meier survival analysis comparing the survival probability of patients without toxoplasmosis with a positive toxoplasma IgG (purple line) to those with a negative Toxoplasma IgG (green line)

Conclusion

Toxoplasma IgG seropositivity without clinical disease is associated with an increased risk of one-year mortality, hospitalization, and schizophrenia diagnosis. Further prospective studies are needed to clarify the association of Toxoplasma exposure with schizophrenia and worse outcomes.

Disclosures

All Authors: No reported disclosures.
372. Analysis of the reliability of rapid diagnostic tests for varicella patients, including breakthrough cases
Authors: Higashimoto Yuki , Hattori Fumihiko , Kawamura Yoshiki , Kozawa Kei , Enya Yasuko , Ihira Masaru , Yoshikawa Tetsushi
Published: December 2022

Background

In the era of universal varicella vaccination, diagnosis of varicella is challenging, especially for breakthrough cases. We sought to clarify the reliability of direct varicella-zoster virus (VZV) loop-mediated isothermal amplification (LAMP) and DermaQuick® VZV using the immunochromatography technique as rapid diagnostic tests for varicella. In addition, the usefulness of saliva as a sample type for direct LAMP was also investigated.

Methods

Between April 2019 and January 2021, 46 patients suspected VZV infection were enrolled in this study. Written informed consent was obtained from the parents of all participants. This study was approved by the institutional review board of Fujita Health University (No. 15–247). Samples were collected from skin eruptions using two different swabs. one swab which was soaked in 1 mL of isotonic saline was used for direct VZV LAMP and the other swab which was immersed in 500 µL of DermaQuick® VZV reaction buffer was used for DermaQuick® VZV. The isotonic saline solution used to wash the oral swab sample was used for direct VZV LAMP. The DNA extracted from the solutions were used for real-time PCR analysis.

Results

Thirty one patients (67.3%) were diagnosed with varicella based on real-time PCR of skin swabs. Direct LAMP of skin swabs was positive in 29 (63.0%) of 46 patients. DermaQuick® VZV was positive in 25 (54.3%) of 46 patients. The sensitivity for direct LAMP of skin swabs, DermaQuick® VZV, direct LAMP of oral swabs, and real-time PCR of oral swabs was 93.6% (95% confidence interval [CI], 79.3–98.9%), 80.7% (95% CI, 63.7–90.8%), 48.3% (95% CI, 32.0–65.1%), and 74.2% (95% CI, 56.8–86.3%), respectively. The sensitivity and specificity of real-time PCR for DNA extracted from oral swabs was 74.2% (95% CI, 56.8–86.3%) and 93.3% (95% CI, 79.8–99.7%), respectively.

Conclusion

Although DermaQuick® VZV is the most convenient point-of-care test for varicella, the sensitivity and specificity of this method were slightly lower than those of direct VZV LAMP.

Disclosures

All Authors: No reported disclosures.
385. Impact of the COVID-19 Pandemic First Wave on Clostridioides difficile Infection
Authors: Mendo-Lopez Rafael , Pacheco Lauren , Villafuerte-Galvez Javier A
Published: December 2022

Background

Clostridioides difficile infection (CDI) is the leading cause of nosocomial diarrhea and a costly burden on the healthcare system. The COVID-19 pandemic brought enhanced infection control measures that could hypothetically decrease CDI transmission. Nonetheless, diarrhea secondary to COVID-19 and increased usage of broad-spectrum antibiotics could potentially increase testing for or frequency of CDI. We aimed to assess variations in CDI testing and frequency during the first surge of the COVID-19 pandemic in a tertiary community medical center in the Southern United States.

Methods

Records from adult patients were retrospectively reviewed at Princeton Baptist Medical Center, Birmingham, AL. Three groups spanning equal time periods were created based on the CDC COVID-19 rate curves for Alabama: PPG (pre-pandemic, 03/01/2020 to 05/31/2020), PG (pandemic, 06/01/2020 to 08/31/2020), and SCG (seasonal control, 06/01/2019 to 08/31/2019). We included patients ≥ 18 years old and excluded readmissions and follow-up visits. We determined the frequency, testing rates, and positivity rates for CDI in each group to assess their differences. Also, we measured the rate of coinfection between C. difficile and SARS-CoV-2. CDI cases were defined as positive toxin enzyme-linked immunosorbent assay (EIA) and glutamate dehydrogenase (GDH), or positivity of either in addition to positive nucleic acid amplification test (NAAT). Differences in frequencies and rates across groups were compared with Fisher exact test.

Results

Overall, 7,252 hospitalized patients and 29,671 outpatients were included (Figure 1). No outpatient CDI cases were detected. Outpatient testing rates were: PPG 3 (0.05%), PG 4 (0.05%), and SCG 9 (0.06%). Among inpatients, 3,912 (53.9%) were female with a mean ± SD age of 61.2 ± 17.5 years. Overall, CDI frequency, testing rates, and positivity rates did not vary significantly among all groups (Table 1). Among those tested, the only case of C.difficile/SARS-CoV-2 coinfection corresponded to PPG. Figure 1:Patient distributionTable 1:Frequency of CDI and COVID-19 infection in inpatients

Conclusion

There were no statistically significant differences in CDI frequency, or positivity rate between the pre-pandemic, pandemic, and seasonal control groups for inpatients. No CDI cases were detected in outpatients. This is likely due to a low testing rate in our population.

Disclosures

All Authors: No reported disclosures.
388. Does This Patient Have C. difficile Infection? A Systematic Review and Meta-Analysis
Authors: Manzoor Fizza , Manzoor Saba , Pinto Ruxandra , Brown Kevin , Langford Bradley J , Daneman Nick
Published: December 2022

Background

The clinical features of Clostridioides difficile infection overlap with many conditions. Accurate and early diagnosis of C. difficile is essential for reducing morbidity and mortality. We performed a systematic review to evaluate the diagnostic utility of clinical findings associated with C. difficile.

Methods

We included all studies that reported clinical features of C. difficile, a valid reference standard test for confirming diagnosis of C. difficile, and a comparison among patients with a positive and negative test result. The MEDLINE, EMBASE, CINAHL, and Cochrane databases were searched up to September 2021. Meta-analyses using univariate and bivariate methods were used to determine estimates of sensitivity, specificity, and likelihood ratios (LRs).

Results

A total of 11,231 articles were screened and 46 were included for final analysis, enabling evaluation of 67 features for their diagnostic utility for C. difficile (10 clinical examination findings, 4 laboratory tests, 10 radiographic findings, prior exposure to 14 antibiotic types, and 29 clinical risk factors). Of the ten features identified on clinical examination, none were associated with increased likelihood of C. difficile infection. Features that increased likelihood of C. difficileinfection were stool leukocytes (LR 5.31, 95% CI 3.29-8.56), hospital admission in prior three months (LR 2.39, 95% CI 1.68-3.30), leukocytosis (LR 1.50, 95% CI 1.24-1.75), and low serum albumin (LR 1.43, 95% CI 1.06-1.97). Some clinical co-morbidities increased likelihood of C. difficile including congestive heart failure (LR 3.01, 95% CI 2.26-3.80) and end-stage renal disease (LR 3.85, 95% CI 1.73-7.57). Several radiographic findings also strongly increased the likelihood of C. difficile infection like pericolonic stranding (LR 10.72, 95% CI 9.59-11.84) and ascites (LR 2.91, 95% CI 1.76-4.80).

Conclusion

There is limited utility of bedside clinical examination alone in detecting or ruling out C. difficile infection. Accurate diagnosis of C. difficile infection requires a combination of thoughtful clinical assessment and interpretation of test results. However, microbiologic testing is needed for confirmation in all suspected cases.

Disclosures

All Authors: No reported disclosures.
396. Incidence and Attributable Mortality of Clostridioides difficile Infection Among US Adults 18-64 Years of Age
Authors: Yu Holly , Alfred Tamuno , Zhou Jingying , Judy Jennifer , Olsen Margaret A A
Published: December 2022

Background

Studies characterizing the burden of Clostridioides difficile infection (CDI) have largely focused on older adults, with limited data among those < 65 years of age insured under commercial plans.

Methods

This retrospective cohort study from 2012–2020 used Optum’s de-identified Clinformatics® Data Mart of about 42 million commercially insured persons. CDI was defined by ICD9/ICD10 diagnosis codes or a combination of CDI diagnosis/testing with antibiotic receipt; cases occurring ≤60 days after prior CDI occurrences were excluded. Annual CDI incidence was evaluated among individuals who were 18–64 years old and enrolled in an Optum commercial plan by January 1 of the corresponding year. Mortality was evaluated in persons with CDI from 2016–2018 who were continuously enrolled in the database for ≥12 months prior; follow-up occurred through the earliest of 12 months, disenrollment, or death. To assess CDI-attributable mortality, CDI+ cases were matched 1:1 to CDI– controls by the propensity score for CDI. Mortality was stratified by age group, acquisition type, and hospitalization status.

Results

CDI incidence was generally stable from 2012–2016 (217–220 and 112–118 episodes per 100,000 person-years (PY) in the 50–64- and 18–49-year age groups, respectively) before decreasing gradually between 2016 and 2020 to 139 episodes per 100,000 PY (50–64-year age group) and to 66 episodes per 100,000 PY (18–49-year age group) (Figure 1). In the 50–64-year age group, CDI-attributable mortality increased to 2.2% at 12 months (CDI+, 4.2%; CDI−, 2.0%), with larger attributable differences observed among hospitalized (healthcare associated [HA], 18.1%; community associated [CA], 7.0%) vs nonhospitalized (HA, 3.3%; CA, −0.1%) patients (Figure 2). The CDI-attributable mortality rate of 0.6% at 12 months among the 18–49-year age group was lower than that in the 50–64-year age group but trended similarly (CDI+, 1.2%; CDI−, 0.6%).

Conclusion

As reported previously, both CDI incidence and attributable mortality among US individuals 18–64 years increased with age. Identifying high-risk groups among non-elderly adults is warranted to develop better strategies for effective prevention.

Funded by Pfizer Inc.

Disclosures

Holly Yu, MSPH, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Tamuno Alfred, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jingying Zhou, MA, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jennifer Judy, MS, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Margaret A A. Olsen, PhD, MPH, Pfizer Inc: Advisor/Consultant|Pfizer Inc: Grant/Research Support.
411. Characterization of Antibiotic Prophylaxis Prior to Trans Rectal Ultrasound Guided Prostate Needle Biopsy (TRUS PNB): A 5-Year Nationwide Study among Patients in the United States Veterans Health Administration
Authors: Issa Jamil Abou , Saroufim Paola , Saade Elie , Donskey Curtis
Published: December 2022

Background

Prophylactic antibiotics are used prior to TRUS PNB to reduce risk for infectious complications such as UTI, prostatitis, epididymitis, orchitis, bacteremia and sepsis. Fluoroquinolones have been commonly used for prophylaxis, however, the incidence of post TRUS PNB infections caused by fluoroquinolone resistant Escherichia coli has increased. The purpose of this study was to characterize the prophylaxis agents used nationwide in the Veterans Health Administration (VHA) prior to TRUS PNB.

Methods

We conducted a review of records of all patients undergoing TRUS PNB in the VHA database from January 1st, 2013 to December 31st, 2018. We collected data about outpatient oral prophylaxis antibiotics, inpatient injectable antibiotics and microbiology results from rectal swabs and urine cultures performed within 90 days prior to the procedure.

Results

Of 153,055 patients undergoing prostate biopsy between January 1st, 2013 and December 31st, 2018, 27.6% (n=42,319) had urine cultures and 3.9% (n=5,294) had rectal swab cultures done within the 90-day window prior to the procedure. Among these who had urine and rectal swabs culture, 3.0% (n=1,292) and 20.1% (n=1,062) were positive for E. coli, respectively; 40.2% of E. coli isolates recovered from urine and 89.6% recovered from rectal swabs were resistant to fluoroquinolones. Table 1 shows the frequencies and percentages of oral prophylactic agents administered within the 90 days prior to the procedure and injectable antibiotics administered on the day of the procedure.

Frequency and percentage of oral prophylactic agents administered within the 90 days prior to the procedure and injectable antibiotics administered on the day of the procedure

Frequency and percentage of oral prophylactic agents administered within the 90 days prior to the procedure and injectable antibiotics administered on the day of the procedure

Conclusion

Despite the high rate of recovery of fluoroquinolone-resistant E. coli in pre-procedure urine and rectal swabs, oral fluoroquinolones remained the most frequently used prophylactic agents prior to TRUS PNB. This inadequate prophylactic coverage may increase the risk of infectious complications following prostate biopsy.

Disclosures

Elie Saade, MD, MPH, FIDSA, Janssen: Advisor/Consultant.
414. Detection of Colonized Patients with Organisms Resistant to Carbapenems by a Fast Molecular Method at a Hospital in Nicaragua.
Authors: López-Navarro Jilmer , Porras-Cortés Guillermo D
Published: December 2022

Background

The resistance to carbapenems has significant implications regard the clinical outcomes of the patients. Strategies to detect colonized patients with carbapenems-resistant organisms are useful to start isolation measures to prevent intrahospital transmission. GeneXpert Carba-R is a fast molecular test to detect rectal colonization by this type of microorganisms. The aim of this study was to detect colonized patients transferred from other countrywide hospitals in Nicaragua, to have an epidemiological panorama of the circulation of genes that confers resistance to carbapenems.

Methods

This is a retrospective cohort study in a referral hospital (Hospital Dr. Fernando Vélez Paiz) in Managua, Nicaragua. The period of the study was between January 2020 and October 2020. Patients referred to our ICU that had been stayed more than 48 hours in the originating health-care center were recruited. Rectal swab were processed by GeneXpert Carba-R to identify any of the genes of resistance (NDM, KPC, VIM, IMP, OXA-48). An association between colonization and clinical outcomes was evaluated.

Results

Eighty-nine patients were included in the study and 27 (30.3%) of them had a positive test of Xpert Carba-R. In four patients more than one gene was detected. The most frequent gene detected was NDM (66.6%). Other detected genes were VIM and KPC. Patients colonized with this kind of microorganims were identified coming from 9 countrywide hospitals and from 6 hospitals of the capital city (Managua). Independent risk factors for colonization by organisms resistant to carbapenems were previous exposition to this class of antibiotic (OR: 9.82; CI95%: 3.29-29.30) and qSOFA ≥ 2 points at the admission (OR: 7.36; CI95%: 2.60-20.76). The mortality in the colonized patients was 33.3% vs 9.6% in the control group (p=0.006), with an odds ratio of 4.6 (CI95%: 1.46-14.90).

Map of Nicaragua showing the wide distribution of the detection of genes conferring resistance to carbapenems in patients referred to Hospital Dr. Fernando Vélez Paiz in the capital city of Managua.

Conclusion

The prevalence of rectal colonization by organisms resistant to carbapenems in patients transferred to a referral hospital in Nicaragua is high. The most frequent gene detected was NDM. There are presence of these genes in countrywide hospitals. The previous use of carbapenems and the severity of the illness at the admission were risk factors for colonization. To be colonized with this microorganism increased the risk to die.

Disclosures

All Authors: No reported disclosures.