bluuebunny/crossref_metadata_2025_split huggingface dataset:
643. Evaluation of Rapid Blood Pathogen Identification Along with Antimicrobial Stewardship at an Academic Teaching Institution
Authors: Blum Sharon , McSweeney Terrence , Tirmizi Samad , Auditore brian , Johnson Diane , Malone Brian 
Published: December 2021

Abstract

Background
Bloodstream infections are a major cause of morbidity and mortality in hospitalized patients. Prompt initiation of effective antimicrobials are essential to optimize patient outcomes. New diagnostic technologies rapidly identifying bacteria, viruses, fungi, and parasites in infections of various body sites. There is a paucity of literature determining if stewardship programs run by one trained pharmacist with rapid diagnostics decreases time to optimal antimicrobial therapy.

Methods
This was a retrospective chart review of positive bloodstream infections identified via rapid diagnostic technologies. The EHR of admitted adult patients with positive BSI identified by BioFire FilmArray Blood Culture Identification (BCID) Panel™ or Accelerate PhenoTest Blood Culture kit™2 between January 2018 – July 2019 were evaluated and pertinent data was collected.

Results
Rapid diagnostic technologies identified 108 bloodstream infections due to gram positive, 56 due to gram negative, and 6 due to Candida organisms. Mean time to optimal antimicrobial therapy was significantly lower when pharmacist recommendation was accepted versus when primary care team consulted ID for recommendation or did not accept pharmacist recommendation. Mean time to optimal therapy was 14.7, 34.3, and 271.3 hours (p&lt; 0.0001) respectively. Median total cost of visit per patient, calculated using the average wholesale price of antibiotics multiplied by the number of doses received, was significantly lower when pharmacist recommendations were accepted (&86.40, &147.95, and &239.41, respectively).
Baseline characteristics

Microbiological isolates

Primary Outcome: Time to Optimal Therapy

Conclusion
The establishment of a pharmacist run antimicrobial stewardship program in conjunction with rapid diagnostic tools for identifying bacteremia led to a decrease in time to optimal antimicrobial therapy and cost savings. Introduction of similar services at community hospitals with limited ASP staffing is justified. Larger studies to further investigate whether ASP partnered with rapid diagnostics have an impact on patient-related outcomes such as mortality and length of stay is warrented.
Secondary outcomes

Missed cost savings

Disclosures
All Authors: No reported disclosures
644. Phenotypic and Genomic Analysis of Novel, Fastidious, Gram-negative Bacilli Isolated from Clinical Wound Specimens
Authors: Liu Benjamin , Simmon Keith , Fisher Mark 
Published: December 2021

Abstract

Background
Animal bites are considered the thirteenth leading cause of nonfatal ED visits. Epidemiology studies have shown a rise in dog bites during the COVID-19 pandemic in the U.S. In Oct. 2020, we received a facultatively anaerobic, non-hemolytic Gram-negative rod (OL1) from a dog bite wound for identification. 16S rRNA gene sequencing showed OL1 was 95.9% identical to Ottowia pentelensis in the family Comamonadaceae. Our historical sequence database revealed 8 additional isolates (OL2-OL9) from hand wounds/abscesses (including 3 dog bites) since 2012 that had ⩾ 99.8% identity with OL1. Most other Ottowia sp. have been isolated from industrial and food sources, with no reports from patient samples. As these clinical isolates likely represent a novel Ottowia species, we aimed to characterize them using both phenotypic and genomic approaches.

Methods
The OL isolates were tested in API 20 NE panels (8 conventional and 12 assimilation tests) for 4 d. Paired-end genomic DNA libraries (Nextera DNA Flex Library Prep, Illumina) were sequenced as 150 nt reads by Illumina NovaSeq. De novo assembly, annotation, functional prediction, and phylogenetic analyses were performed with Geneious, PATRIC, and web-prediction databases. Strain comparison was done with StrainTypeMer.

Results
All 9 OL isolates were negative for indole, urea, arginine, esculin, PNPG, glucose fermentation and carbohydrate assimilation tests. Potassium gluconate assimilation and gelatin hydrolysis were positive for 5 and 4 isolates, respectively. StrainTypeMer showed the isolates from different patients were not closely related, but 2 from the same patient were indistinguishable. The estimated genome size was ~3.1 Mbp, with 66.1% G/C, and ~3523 coding genes. Potential virulence factors (BrkB and MviM), multidrug efflux systems (MdtABC-TolC and Bcr/CflA), and 1-2 intact prophages were identified. Genomic phylogenetic analysis with RAxML showed the OL isolates clustered separately from all known Ottowia spp.

Conclusion
These OL isolates are fastidious, Gram-negative bacilli from clinical wound specimens, and are associated with dog bites. Genomic and 16S rRNA gene sequence analysis suggests these isolates constitute a novel species within the family Comamonadaceae.

Disclosures
All Authors: No reported disclosures
646. Increasing Use of Interferon-Gamma Release Assay to Test for Pediatric Tuberculosis in a Low-Burden Setting
Authors: Campbell Jeffrey , Sun Mingwei , He Wei , Lamb Gabriella S , Lamb Gabriella S , Tabatneck Mary , Goldmann Don , Sabharwal Vishakha , Sandora Thomas , Haberer Jessica 
Published: December 2021

Abstract

Background
The American Academy of Pediatrics recommends tuberculin skin tests (TSTs) or interferon gamma release assays (IGRAs) to test for tuberculosis (TB) infection in children ≥2 years old, and prioritizes IGRA testing in Bacille Calmette-Guérin vaccine recipients due to cross-reactivity. TSTs require a return visit, which frequently results in loss to follow up. Growing evidence supports accuracy of IGRA testing in pediatric patients, including young children, leading to calls for preferential use of IGRA over TST. We sought to evaluate trends in IGRA use in children over time.

Methods
We identified all TB infection tests conducted in children 5-17 years old at 2 academic medical systems in Boston from October 2015–January 2021. TSTs were identified using medication administration records, and IGRAs were identified using laboratory records. We computed the proportion of tests per month that were IGRA and TST. We used Pearson correlation to determine the association between month of testing and proportion of tests that were IGRAs.

Results
21,471 TB infection tests were obtained from 16,778 patients during our timeframe. Median age of testing was 13.4 years (IQR 9.2 – 16.2 years). During the study period, there was a significant increase in the monthly proportion of TB infection tests that were IGRAs (Pearson correlation coefficient 0.92, P &lt; 0.001). The total number of tests performed per month also increased, with seasonal increases in testing in late summer and early fall and a substantial decline in testing early in the COVID-19 pandemic.
Tuberculosis infection tests and proportion IGRA.

Total number of tuberculosis infection tests per month and proportion of tests that were interferon gamma release assays, from October 2015 - January 2021.

Conclusion
Use of IGRAs among patients age 5-17 years of age increased significantly overall and compared to TST in two large Boston healthcare systems over a 5-year period. These results suggest a shift towards blood-based TB infection testing in a low-burden setting, which may improve completion of the pediatric TB infection care cascade. Future research is needed to determine reasons for changing testing modalities, and similar patterns in other settings.

Disclosures
Gabriella S. Lamb, MD, MPH, Nothing to disclose
647. Investigation of Heteroresistance Among Klebsiella pneumoniae (KP) Inner Colonies (IC) Observed During Fosfomycin Disk Diffusion (DD) Testing
Authors: Bixby Morgan L , Krueger Amanda , Hirsch Elizabeth B 
Published: December 2021

Abstract

Background
During fosfomycin DD testing, the frequent occurrence of non-susceptible IC within the zone of inhibition of susceptible isolates has been noted. The Clinical & Laboratory Standards Institute (CLSI) and European Committee on Antimicrobial Susceptibility Testing (EUCAST) have contradicting recommendations on how IC should be interpreted; CLSI recommends considering IC when interpreting DD results whereas EUCAST recommends ignoring them. This study sought to identify the susceptibility of these IC and to understand whether heteroresistance contributes to the appearance of IC during fosfomycin DD.

Methods
This study included a convenience sample of 71 KP clinical isolates from 3 United States locations. During DD testing, 58 (81.7%) of these isolates displayed at least one IC. Broth microdilution (BMD) minimal inhibitory concentration (MIC) testing, using extrapolated CLSI Escherichia coli breakpoints, was performed on a subset (n=32) of the IC in duplicate for comparison to the corresponding parent MIC values. This was followed by a modified disk elution screening test for heteroresistance to compare the frequency of low level resistance (LLR) and high level resistance (HLR) between the susceptible isolates that produced resistant IC (n=6) and those that did not produce any IC (n=3).

Results
The MIC range for the IC isolates (128 to &gt; 1024 μg/mL) increased as compared to the parent isolates (&lt; 2 to &gt; 256 μg/mL) and MIC50/90 increased from the parent (128/ &gt; 256 μg/mL) to IC (1024/ &gt; 1024 μg/mL) isolates. All IC isolates had a resistant MIC value vs. 46.5% of parent isolates, and over 90% of IC isolates had an MIC at least 2 dilutions higher than their corresponding parent isolate. Heteroresistance screening found all tested isolates to be positive for LLR, and 8 of 9 positive for HLR, while the one HLR-negative isolate was IC-producing.

Conclusion
IC were frequent during fosfomycin DD testing and were commonly more resistant than their corresponding KP parent isolates. A small subset of these isolates tested via a modified disk elution test displayed either LLR or HLR regardless of the absence of IC. These results call for further investigation among a larger isolate set to understand what mechanisms are responsible for the frequency of IC and their increased fosfomycin resistance.

Disclosures
All Authors: No reported disclosures
650. LiaX as a Surrogate Marker of Daptomycin Susceptibility in Multidrug-Resistant Enterococcus faecium
Authors: Axell-House Dierdre B , Khan Ayesha , Shelburne Samuel A , Shamoo Yousif , Tran Truc T , Arias Cesar A 
Published: December 2021

Abstract

Background
Vancomycin-resistant Enterococcus faecium (VREfm) are important causes of bloodstream infections (BSI) in patients (pts) with cancer, liver disease, and foreign bodies. Daptomycin (DAP) is commonly used to treat VRE BSI, but DAP resistance (DAP-R) is increasing. Current methods to determine DAP minimum inhibitory concentrations (MICs) have poor reproducibility. DAP triggers the LiaFSR cell membrane stress response pathway, resulting in the extracellular release of LiaX, a protein that functions as a sentinel molecule for DAP, and controls the cell membrane response.

Methods
We used 6 reference Efm isolates to optimize a whole-cell enzyme-linked immunosorbent assay (ELISA) method for LiaX detection. We then assessed 86 clinical Efm BSI isolates recovered from 3 hospitals in Houston and Detroit for DAP MICs and used whole genome sequencing to assess for substitutions in LiaFSR/LiaXYZ proteins. We collected patient and microbiological data by chart review.

Results
All DAP-R reference strains had increased detection of LiaX compared to DAP-S strains (p&lt; 0.0001). Of the 86 pts with Efm BSI, 73.2% had malignancy, 9.3% had liver disease, and 76.7% had foreign bodies. The source of 52.3% of BSIs was determined to be gastrointestinal. Two of the 86 isolates were DAP-R by CLSI breakpoints. The LiaX test and DAP MICs had a categorical agreement in 62.8% of isolates. All isolates with discordant ELISA/MIC results had DAP-S MIC (median 2, IQR 1-3)but increased LiaX. Using the genomic information, we identified 41 sites of amino acid (AA) changes in the LiaFSR/XYZ proteins of the ELISA/MIC discordant isolates. The substitutions LiaR S19F and LiaS E153K/D251E were associated with discordancy (p=0.0036 and p=0.0018, respectively).

Conclusion
Detection of LiaX is likely to indicate activation of the DAP-mediated cell membrane response in Efm and may be an indicator of DAP-R. Important discrepancies between LiaX and standard DAP MIC determination were found, highlighting the limitation of MIC determination. Further characterization of the discrepant isolates by time-kill assays and evaluation of patient clinical outcomes are warranted to fully validate the performance and clinical utility of the LiaX ELISA.

Disclosures
Truc T. Tran, PharmD, Merck (Grant/Research Support) Cesar A. Arias, M.D., MSc, Ph.D., FIDSA, Entasis Therapeutics (Grant/Research Support)MeMed Diagnostics (Grant/Research Support)Merk (Grant/Research Support)
651. Clinical Characteristics and Susceptibility Profiles of Infections Due to Elizabethkingia
Authors: Comba Isin Y , Castillo Almeida Natalia E , Stevens Ryan W , Shah Aditya 
Published: December 2021

Abstract

Background
Elizabethkingia spp. are non-enteric, gram-negative bacilli that are ubiquitous in environment. It has recently been identified as a causative pathogen in hospital outbreaks of life-threatening bloodstream infections in the Midwestern United States.

Methods
Retrospective electronic medical record review was performed for patients with Elizabethkingia spp. isolated from any site between November 2011 and September 2020 at our tertiary academic medical center. Antimicrobial susceptibilities are performed using Wadsworth agar dilution method.

Results
Fifteen cases with Elizabethkingia spp. were included. Ten patients (66.7%) were male and fourteen (93.3%) were Caucasian. The median age was 58 years (IQR 42-67). Four patients had diabetes mellitus, with two of these having end-organ damage (nephropathy, neuropathy, or retinopathy). Five patients had a tracheostomy, two patients had a history of lung transplantation, and four patients had active malignancy at the time of diagnosis (table 1). The most common clinical syndrome was respiratory infection (n=6), followed by catheter-related bloodstream infection (CRBSI) (n=4). Three patients were considered to be asymptomatically colonized. Five patients (33.3%) died, one of which was attributable to Elizabethkingia infection. A total of 55 isolates from all sites were available from the fifteen patients. The most common site of isolation was respiratory tract (23/55, 41.8%). In total, 33 of 55 isolates had polymicrobial growth, with the highest rate occurring in respiratory tract specimens (Table 2). A total of 23 clinical isolates were included in tabulation of antimicrobial susceptibility profiles; except for aztreonam (n=13). 95.7% of Elizabethkingia isolates were susceptible to trimethoprim-sulfamethoxazole, followed by levofloxacin and piperacillin-tazobactam (87% and 73.9%, respectively). All isolates were uniformly resistant to amikacin, aztreonam, and tobramycin (Table 3).

Conclusion
Elizabethkingia spp. can result in respiratory, bloodstream, and sinus infections especially in patients with active malignancy and tracheostomy. Amongst tested antimicrobials, trimethoprim-sulfamethoxazole showed the most favorable susceptibility profile (Figure 1).
Figure 1.

AN, amikacin; ATM, aztreonam; CAZ, ceftazidime; CIP, ciprofloxacin; FEP, cefepime; GM, gentamicin; LVX, levofloxacin; MEM, meropenem; NN, tobramycin; SXT, sulfamethoxazole/trimethoprim; TZP, piperacillin/tazobactam.

Disclosures
All Authors: No reported disclosures
654. Performance of the T2Resistance Panel in Detecting Antibiotic Resistant Bacteria Directly in Whole Blood, and Implications for Improving Appropriate Therapy of Bloodstream Infections
Authors: Skeel Abigail , Clancy Cornelius J , Lucas Aaron , Hughes Kailey L , Shields Ryan K , Nguyen Minh-Hong 
Published: December 2021

Abstract

Background
Appropriate antibiotic (Ab) therapy of bloodstream infections (BSI) is often delayed by time to blood culture (BC) positivity, species (sp) identification and Ab sensitivity (sensi). The T2Resistance (T2R) Panel is a direct-from-blood (culture-independent) diagnostic that detects 13 genetic markers associated with methicillin-resistant S. aureus (MRSA), vancomycin-resistant Enterococcus (VRE), ESBL- and carbapenemase-producing Enterobacteriaceae (E). We assessed T2R performance in detecting these resistant bacteria in whole blood (WB) and analyzed possible impact on time to appropriate Ab.

Methods
We performed T2R using WB samples obtained from patients (pts) on the same day as BCs from July 2019-2020. Receipt of appropriate Ab was assessed at time of empiric, Gram stain-directed, MALDI-directed (sp identification) and sensi-directed therapy. T2R results were not available to care teams. Teams were notified of positive BCs. Stewardship optimized Abs based on sensi.

Results
BC from 103 pts grew 114 bacterial sp: E (n=54; 16 ESBL-, 1 KPC-producer), S. aureus (n=29, 22 MRSA), Enterococcus (n=21, 16 VRE), P. aeruginosa and others (n=10). 12 ESBL-E produced CTX-M 14/15. T2R sensitivity and specificity was 78% and 99%, respectively, compared to sequencing of resistance markers. Sensitivity was excellent for vanA/B, KPC (100% each), and CTX-M14/15 (92%); sensitivity was 58% for mecA/C. T2R detected resistance determinants in 3-7h. Median time to appropriate Ab was 16.3h, which was significantly longer for VRE (25.6h) and ESBL- or KPC-E (50.9h) BSIs than for T2R marker-negative bacteria (6.7h; p=0.04). Pts with VRE or ESBL-/KPC-E BSI were less likely to received appropriate empiric Ab (18% and 30%, respectively) than pts with T2R marker-negative BSI (63%; p=0.02; Fig.1). Median times to achieve ≥80% appropriate Ab therapy of marker-negative, VRE and CTX-M/KPC-E BSIs were 15.5h (after Gram stain), 43.9h (after MALDI) and 63.5h (after sensi), respectively.
Antibiotic Therapy

Conclusion
There was a significant delay in appropriate Ab therapy of BSIs, especially in pts infected with VRE and ESBL/KPC-E. T2R rapidly and accurately detected BSI caused by VRE and ESBL/KPC-E, and has the potential to significantly shorten time to appropriate Ab.

Disclosures
Cornelius J. Clancy, MD, Merck (Grant/Research Support) Ryan K. Shields, PharmD, MS, Shionogi (Consultant, Research Grant or Support) Minh-Hong Nguyen, MD, Merck (Grant/Research Support)
655. Patterns of Interferon-Gamma Release Assay (IGRA) Testing for Tuberculosis in Patients Less Than 2 Years Old
Authors: Tabatneck Mary , Campbell Jeffrey , Sun Mingwei , He Wei , Lamb Gabriella S , Lamb Gabriella S , Goldmann Don , Sabharwal Vishakha , Sandora Thomas , Haberer Jessica 
Published: December 2021

Abstract

Background
The American Academy of Pediatrics recommends use of Interferon-Gamma Release Assays (IGRAs) to diagnose tuberculosis (TB) infection in patients ≥2 years old. However, IGRAs are not currently recommended in younger patients due to limited data and concerns of invalid/indeterminate test results, which occur if there is a positive or negative control failure. We sought to characterize the patterns of IGRA use in clinical practice and results of IGRAs in patients &lt; 2 years old.

Methods
We conducted a retrospective cohort study of children &lt; 2 years old at two large health systems in the Boston area who had IGRA and/or tuberculin skin test (TST) performed from October 1, 2015 – January 31, 2021. We reviewed medical records to determine IGRA test type, IGRA result (positive, negative, invalid/indeterminate) and location of testing (outpatient primary care, outpatient subspecialty, inpatient). We summarized test interpretability, location, and changes in proportion of IGRA vs. TST.

Results
We identified 330 IGRA (268 T-SPOT.TB, 62 QuantiFERON Gold) and 2029 TST results among 1982 patients who were &lt; 2 years old (range: 11 days – 1.9 years). Monthly proportion of IGRAs among all TB tests ordered increased from 2015 to 2021 (Figure 1) (Pearson correlation coefficient 0.85, P &lt; 0.001). Among IGRA results, 314 (95%) were negative, 3 (1%) were positive, and 13 (4%) were invalid/indeterminate (11 T-SPOT.TB, 2 QuantiFERON Gold). Of 324 IGRA tests for which testing location was known, 233 (72%) and 91 (28%) were ordered in outpatient and inpatient settings, respectively. Of tests in outpatient settings, 132 (57%) were ordered in primary care offices, 53 (23%) were ordered in subspecialist offices, and 48 (21%) were obtained in outpatient labs of unidentified clinics.
Tuberculosis infection tests and proportion IGRA.

Total number of tests and proportion of IGRA:TST obtained by month, from October 2015-January 2021.

Conclusion
While most TB infection tests in this age group were TSTs, the monthly proportion of tests that were IGRAs increased over time between 2015-2021. IGRAs were obtained in varied clinical settings. In this low-burden setting, rates of invalid/indeterminate IGRAs were low among children &lt; 2 years old, which suggests that IGRAs are reasonable TB testing options for patients &lt; 2 years old, and may be preferred given limitations of TSTs.

Disclosures
Gabriella S. Lamb, MD, MPH, Nothing to disclose
656. Sulbactam-Durlobactam MIC Determination: Comparative Evaluation of the New ETEST® SUD to the CLSI 2021 Broth Microdilution Method
Authors: Sauvonnet Veronique , Escoffier Elodie , Franceschi Christine , Halimi Diane , Martelin Roland , Pellet Laetitia , Zambardi Gilles 
Published: December 2021

Abstract

Background
Species belonging to the Acinetobacter baumannii-calcoaceticus (ABC) complex, such as A. baumannii, A. pittii and A. nosocomialis, are a major cause of hospital acquired infections and outbreaks with increasing occurrence of multidrug-resistance. Sulbactam-durlobactam (SUD), a combination of one active β-lactam antibiotic (sulbactam) with a new β-lactamase inhibitor (durlobactam), is currently being tested in a phase 3 clinical trial by Entasis Therapeutics for the treatment of serious infections caused by ABC, including multidrug-resistant strains. At the same time, an ETEST® SUD (sulbactam-durlobactam - MIC range 0.004/4-64/4 µg/mL) has been developed and calibrated versus the broth microdilution reference method (BMD) as described by the Clinical and Laboratory Standards Institute (CLSI). This test is intended to determine the MIC of sulbactam-durlobactam for species of the ABC complex. The aim of this study was to perform a first comparative study of ETEST SUD with the CLSI BMD method on a panel of 263 isolates.

Methods
The panel consisted of 204 A. baumannii, 29 A. pittii, 30 A. nosocomialis, including 24 SUD-resistant strains, and one CLSI QC strain. BMD was performed using the 2021 CLSI guidelines. ETEST SUD was evaluated using the standard ETEST procedure for Acinetobacter spp. (inoculum 0.5 McFarland, Mueller Hinton medium, incubation at 35°C for 20-24h). For each method, the MIC was read at complete inhibition of visible growth. To determine category agreement (CA) and error rates, the sulbactam-durlobactam provisional breakpoint of 4 µg/mL was applied.

Results
The QC strain MICs were in the expected range with reproducible results. The essential MIC agreement [EA, ±1 dilution] was 97.7% without any tendency to over- or underestimate the MIC when compared to BMD. The CA was 98.5%. Two Very Major Errors, both within the EA, and two Major Errors, one within the EA, were observed.

Conclusion
In this study, the ETEST SUD was found to be equivalent to the CLSI reference method. MIC end points were easy to read. With a 15-dilution range and simplicity of use, ETEST SUD could represent a valuable tool for MIC determination and could be an alternative to BMD.
For Research Use Only. The performance characteristics of this product have not been established yet.

Disclosures
All Authors: No reported disclosures