bluuebunny/crossref_metadata_2025_split huggingface dataset:
2240. Implementation of a Clinical Decision Support Panel for Urine Culture Ordering
Authors: Yarrington Michael E , McClellan Fabienne , Dunkerson Tray , Reynolds Staci S , Polage Christopher R , Smith Becky A , Seidelman Jessica , Lewis Sarah S , Advani Sonali D 
Published: December 2022

Abstract

Background
Standard urine culture collection techniques have a high risk of false positive results in catheterized patients. IDSA guidelines recommend replacing long-term catheters before specimen collection for cultures. Our goal was to evaluate the impact of clinical decision support (CDS) during the urine culture computerized provider order entry (CPOE) on test use and patient-level outcomes.

Methods
In March 2021, CDS was added to the urine culture CPOE in the electronic health record (EHR). The order panel includes education regarding appropriate clinical indications for urine culturing, and protocolizes urine collection to determine (A) if a urinalysis was ordered, (B) if special patient population (i.e., PICU), (C) the presence and duration of an indwelling urinary catheter, and (D) whether the catheter had difficulty with placement. Depending on the criteria identified in A, B, C, and D, the panel recommends catheter removal prior to urine culture (Figure 1). We retrospectively evaluated the impact of panel implementation in our pre- (7/2020- 3/2021) and post-intervention periods (4/2021- 3/2022) using an interrupted time series analysis with Poisson regression. Outcomes included urine cultures/1000 patient days (pd), number of catheter removal orders, catheter-associated urinary tract infection (CAUTI)/1000 catheter days, and days of antibiotic therapy with urinary tract infection (UTI) indication/1000pd
Order Panel Framework

Results
Clinicians selected catheter removal in 183 of 2133 (8.5%) instances of ordering a urine culture when a catheter was detected by the panel (Figure 2). Analysis revealed a significant decrease in urine culture orders (1.1% decrease/month, p&lt; 0.05), a decreasing trend of antibiotic use with UTI indications (Figure 3, 2.8% decrease/month, p&lt; 0.05), but no significant change in CAUTI rates (Figure 4). Evaluation of the safety reporting system revealed no identifiable increase in safety events related to catheter removal or reinsertion.

Catheter Associated Urinary Tract Infections
Black boxes indicate Poisson regression model estimates

Black boxes indicate Poisson regression model estimates

Conclusion
CDS can aid in improving urine culture practice habits, including removal of long-standing catheters before urine culture. The decreasing trend in total urine culture orders (Figure 5) may reflect a ”culture change” over time to avoid urine cultures in inappropriate instances.
Total Urine Cultures Ordered
Black boxes indicate Poisson regression model estimates. Red circles indicate predicted outcome without ‘intervention’.

Disclosures
Sonali D. Advani, MBBS, MPH, FIDSA, Locus Biosciences: Advisor/Consultant|Locus Biosciences: Honoraria|Sysmex America: Advisor/Consultant.
108. Immune Status of Indian Pediatric Health Care Workers against Various Vaccine Preventable Diseases
Authors: Verma Sanjay , Sachdeva Ravinder Kaur , Mahajan Vidushi , Rawat Amit , Nehra Urvashi , Subramani Vignesh , Jassal Monika , Bharti Bhavneet 
Published: December 2022

Abstract

Background
Health care workers (HCWs) possess a potential risk to acquire and spread various infections. This study was planned to assess the immune status of HCWs in pediatric departments of two tertiary care hospitals in Northern India.

Methods
In this cross-sectional study, HCW’s (Indians), working in pediatric departments of these hospitals, over 6-months period (July18-Dec18) were enrolled after taking written consent and their 5-ml venous blood sample was collected. Ethical clearance was obtained from Institute Ethics committee, before enrolling subjects. Serum were tested for antibodies against diphtheria-toxin (DT), pertussis-toxin (PT), measles, mumps, rubella, varicella, hepatitis-B (HbsAb) and hepatitis-A using commercial IgG (quantitative) ELISA kits.

Results
A total of 160 HCW’s (M:F=77:83), having mean age 30.6±7.8 years, were enrolled. Out of them 106 (66.3%) were resident doctors, 31 (19.4%) nursing-staff, 18 (11.3%) faculty members, 3 (1.9%) research-staff and 2 (1.3%) paramedical-staff. In our study, antibodies (IgG) against DT were between 0.01 to 0.1 IU/ml in 78.1% (120/160); requiring a Tdap booster; while 7 out of 125 had titers &lt; 0.01 IU/ml, which needed 3-doses of primary vaccination. Antibodies (IgG) against PT &lt; 30 IU/ml were seen in 60.6% (97/160), which were considered as seronegative, as per kit recommendations.
A total of 3% (5/160), 13.1% (21/160), 10% (16/160), 17.5% (28/160) had titers &lt; 12 IU/ml for IgG antibodies against measles, mumps, rubella and varicella respectively; were considered unprotected. A total of 25% (40/160) had Anti-HBs antibody titers &lt; 20 mIU/ml; which were low, therefore were advised to take one booster dose of Hep-B vaccine. A total of 15.6% (25/160) had IgG antibodies against hepatitis-A &lt; 10 mIU/ml; were unprotected.

Conclusion
Alarming proportions of pediatric-HCWs had low antibody titres against DT (78.1%) and PT (60.6%), necessitating a dose of Tdap. A total of 10%, 17.5% and 15.6% lacked protective antibodies against rubella, varicella and hepatitis-A. A quarter of screened population had low anti-Hbs titres, requiring boosting of immunity. Our study emphasizes the urgent need for improving immunization status of pediatric HCW’s; as they continue to remain susceptible to various vaccine preventable infectious diseases.

Disclosures
All Authors: No reported disclosures.
LB747. Immune Responses of the Recombinant MVA-BN-RSV Vaccine against Respiratory Syncytial Virus Infection in an RSV Human Challenge Trial (HCT) in Healthy Adult Participants
Authors: Schmidt Darja , Silbernagl Günter , Jordan Elke , Jenkins Victoria A , Schultz Stephanie , Weidenthaler Heinz 
Published: December 2022

Abstract

Background
Respiratory Syncytial Virus (RSV) causes considerable morbidity and mortality in infants and older adults. Even though throughout life multiple infections occur, there is no natural protection. The MVA-BN vector-based RSV vaccine was designed to induce humoral and cellular RSV-specific immune responses against 5 RSV proteins (F, G [A and B subtype], M2-1 and N). We present immune response data after vaccination and challenge with an RSV-A strain in a human challenge trial conducted in healthy, young adults.

Methods
In a double-blinded, placebo controlled, HCT (EudraCT-no. 2020-004814-36) subjects (N=61) were randomly vaccinated with MVA-BN-RSV or placebo (30 MVA-BN-RSV and 31 placebo), intranasally challenged with RSV-A (Memphis-37b strain) after 28 days and quarantined for 12 days. Exploratory endpoints included RSV specific humoral and cellular immune responses after vaccination and after challenge throughout follow up until Day 155 assessed by treatment group and infected vs non infected in subjects receiving either MVA-BN-RSV or placebo.

Results
For all serum-based RSV specific antibody assays including ELISA IgG, IgA and neutralizing antibody assays PRNT A and B, antibody titers increased after vaccination in the MVA-BN-RSV group and stayed above baseline level over the entire study without being influenced by the challenge with Memphis-37b. In the placebo group, the antibody titers increased after challenge and were not affected by vaccination.
The geometric mean spot forming units (GMSFUs) based on IFN-γ producing PBMCs for the stimulating agents pool F, G(A), G(B), N, M2-1 and RSV increased after vaccination in the MVA-BN-RSV group, peaking at Day 7 post vaccination for most peptide pools without any effect after challenge. In the placebo group, there was no increase after vaccination, but an increase with a peak on Day 10 post challenge was observed for all pools.

Conclusion
The results confirmed the broad humoral and cellular immune response elicited by the vaccination with MVA-BN-RSV which was not further boosted by the challenge virus.

Disclosures
Darja Schmidt, PhD, Bavarian Nordic: Employed|Bavarian Nordic: Warrants Günter Silbernagl, MSc, Bavarian Nordic: Employed|Bavarian Nordic GmbH: employee Employee and received warrants Elke Jordan, PhD, Bavarian Nordic: Employed Victoria A. JENKINS, PhD MBA, Bavarian Nordic: Employed Stephanie Schultz, Dipl Biol, Bavarian Nordic: Employed Heinz Weidenthaler, Dr med, Bavarian Nordic: Employed.
LB1528. Results from ACTIV-6: A Decentralized, Double-Blinded, Randomized, Placebo-Controlled Platform Trial of Repurposed Drugs for the Treatment of Mild-to-Moderate COVID-19
Authors: McCarthy Matthew W 
Published: December 2022

Abstract

Background
The effectiveness of fluvoxamine to shorten symptom duration or prevent hospitalization among outpatients with mild-to-moderate coronavirus 2019 (COVID-19) is unclear. Tolerability has also been identified as a potential limiting factor for 100 mg twice daily of fluvoxamine. We evaluated the efficacy of low-dose fluvoxamine 50 mg twice daily for 10 days compared with placebo for the treatment of early mild-to-moderate COVID-19.

Methods
ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial testing repurposed medications in outpatients with confirmed SARS-CoV-2 infection. Non-hospitalized adults aged ≥ 30 years, experiencing ≥ 2 symptoms of acute infection for ≤ 7 days were randomized to fluvoxamine 50 mg twice daily for 10 days or placebo. The primary outcome was time to sustained recovery, defined as the third of 3 consecutive days without symptoms. Secondary outcomes included composites of hospitalization or death with or without urgent care or emergency department visit by day 28.

Results
Of those eligible for the fluvoxamine arm, 675 were randomized to and received fluvoxamine; 619 received concurrent placebo. Sixty-six percent of the study population reported at least 2 doses of a COVID-19 vaccine. There was no evidence of improvement in time to recovery with fluvoxamine compared with placebo (hazard ratio [HR] 0.96, 95% credible interval [CrI] 0.86–1.06; posterior probability for benefit [HR &gt; 1]=0.2). Sixteen participants (2.4%) in the fluvoxamine arm had urgent care or emergency department visits or were hospitalized compared with 11 (1.8%) in the pooled, concurrent placebo arm (HR 1.5, 95% CrI 0.5–3.0; posterior probability for benefit [HR &lt; 1]=0.1725). No participant in either arm was hospitalized, and no deaths occurred. Adverse events were uncommon in both arms.

Conclusion
Treatment with low-dose fluvoxamine 50 mg dosed twice daily for 10 days did not result in improved time to recovery among outpatients with COVID-19 in the United States during the delta and omicron variant surges.

Disclosures
All Authors: No reported disclosures.
LB1528C. Ivermectin for Treatment of Mild-to-Moderate COVID-19 in the Outpatient Setting A Decentralized, Placebo-controlled, Randomized, Platform Clinical Trial
Authors: Naggie Susanna 
Published: December 2022

Abstract

Background
The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the United States with mild-to-moderate symptomatic coronavirus disease 2019 (COVID-19) is unknown. We evaluated the efficacy of ivermectin 400 µg/kg daily for 3 days compared with placebo for the treatment of early mild-to-moderate COVID-19.

Methods
ACTIV-6 is an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial to evaluate repurposed therapies in outpatients with mild-to-moderate COVID-19. Non-hospitalized adults age ≥ 30 years with confirmed COVID-19, experiencing ≥ 2 symptoms of acute infection for ≤ 7 days were randomized to receive ivermectin 400 µg/kg daily for 3 days or placebo. The main outcome measure was time to sustained recovery, defined as achieving at least 3 consecutive days without symptoms. Secondary outcomes included a composite of hospitalization or death by day 28.

Results
Of the 3457 participants who consented to be evaluated for inclusion in the ivermectin arm, 1591 were eligible for this study arm, randomized to receive ivermectin 400 µg/kg (n=817) or placebo (n=774), and received study drug. Of those enrolled, 47% reported receiving at least 2 doses of SARS-CoV-2 vaccination. The posterior probability for any improvement in time to recovery was 0.91 (hazard ratio 1.07, 95% credible interval 0.96–1.17). The posterior probability of this benefit exceeding 24 hours was less than 0.01, as measured by the difference in mean time unwell. Hospitalizations or deaths were uncommon (ivermectin [n=10]; placebo [n=9]). Ivermectin at 400 µg/kg was safe and without serious adverse events as compared with placebo (ivermectin [n=10]; placebo [n=9]).

Conclusion
Ivermectin dosed at 400 µg/kg daily for 3 days resulted in less than one day of shortening of symptoms and did not lower incidence of hospitalization or death among outpatients with COVID-19 in the United States during the delta and omicron variant time periods.

Disclosures
Susanna Naggie, MD/MHS, AbbVie: Grant/Research Support|BMS/PRA: Event adjudication|Gilead Sciences: Grant/Research Support|Pardes Biosciences: Advisor/Consultant|Personal Health Insights, Inc: Data Safety Monitoring Board Member|Silverback Therapeutics: Advisor/Consultant|Vir Biotechnology: Advisor/Consultant|Vir Biotechnology: Stocks/Bonds.
127. Antimicrobial Efficacy Against Antibiotic-Tolerant Staphylococcus aureus Depends on the Mechanism of Antibiotic Tolerance
Authors: Meredith Emily M , Harven Lauren T , Berti Andrew D 
Published: December 2022

Abstract

Background
Bacteria can adopt an alternate metabolic state favoring small molecule synthesis over growth. In Staphylococcus aureus this is induced by factors present during infection including nutritional limitation and competition with other bacteria. Isogenic “tolerant” subpopulations have variable responses to antibiotics and can remain viable. Survivors resume growth upon cessation of antibiotics and cause relapse or recurrent infection. In this study we compare the capability of antibiotics to reduce viability of S. aureus made tolerant by different mechanisms.

Methods
Overnight cultures of S. aureus SH1000 were diluted to 106 cfu/mL. Tolerance was induced with mupirocin or 2-n-heptyl-4-hydroxypuinoline N-oxide (HQNO) simulating nutritional or competitive tolerance, respectively. Tolerant cultures were exposed to ceftaroline, daptomycin, gentamicin, levofloxacin, oritavancin or vancomycin at physiological concentrations and viability assessed by dilution plating. Minimum duration for 3-log viability reduction (“bactericidal activity”, MDK99.9) and 24h viability reduction were calculated independently for each of three biological replicates. Significance (P &lt; 0.05) was determined using Student’s t-test.

Results
Time to bactericidal activity was prolonged for all antibiotics tested against nutritionally-tolerant S. aureus. Time to bactericidal activity was similarly prolonged against competitively-tolerant S. aureus, although the MDK99.9 of oritavancin was not affected. Viability reduction was mitigated for all antibiotics tested against nutritionally-tolerant S. aureus with the exception of oritavancin. In contrast, 24h viability reduction of competitively-tolerant S. aureus only occurred with ceftaroline, gentamicin and vancomycin while daptomycin, levofloxacin and oritavancin remained equally potent.

Conclusion
Tolerance can alter both the time to bactericidal effect and the extent of killing. Both the antibiotic and the mechanism of tolerance impact time to bacterial effect and extent of killing. Oritavancin was the only antibiotic that maintained the same extent of killing regardless of tolerance mechanism. Further studies to evaluate additional antistaphylococcal antibiotics and different inducers of tolerance are warranted.

Disclosures
All Authors: No reported disclosures.
149. Increasing Oxacillin Resistance of Staphylococcus lugdunensis Over Time, Utilizing Whole Genome Sequencing to Characterize Resistance
Authors: Constance Kristin , Fukuta Yuriko , Penner Elizabeth , Lasco Todd M , Wanger Audrey , Hanson Blake M , Nigo Masayuki 
Published: December 2022

Abstract

Background
Staphylococcus lugdunensis (SL) is a coagulase negative staphylococci (CoNS) demonstrating more virulent pathogenicity compared to other CoNS. With implementation of rapid diagnostics such as multiplex PCR on blood culture and use of MALDI-TOF (MALDI), CoNS can now be routinely specifically identified as SL. We sought to describe the antibiotic susceptibility of SL over time, and to utilize whole genome sequencing (WGS) to identify the characteristics of oxacillin (OXA) resistant SL.

Methods
Retrospective review of all culture isolates positive for SL from two major hospital systems, Memorial Hermann Hospital System (MHHS) and Baylor St. Lukes Medical Center (BSLMC) in Houston, TX. MALDI was implemented in 2016 at BSLMC and 2019 at MHHS. MHHS utilizes Microscan®, and BSLMC utilizes Vitek2® for susceptibility testing. For this study, all duplicated isolates within a 2-week period were excluded. Six patient isolates, three OXA resistant and three susceptible, were sent for WGS and analysis.

Results
Between 2014 and 2021, 744 culture isolates were identified as SL, 325 from MHHS and 419 from BSLMC (Fig 1). An increasing trend was observed at MHHS over time, however this trend was not observed at BSLMC. 83.6% (622/744) of isolates were susceptible to OXA. An overall trend towards increasing resistance was observed over time (Fig 2). Six isolates, three OXA susceptible (S) and three resistant (R), were sent for WGS. The R isolates were found to share the same sequence type (ST3), and while they were not clonal, were closely related and all harbored an SCCmec cassette most closely related to SCCmec type IVg.

Conclusion
In our study, an increasing number of isolates were identified at MHHS over time. This finding may be related to implementation of MALDI. Overall OXA susceptibility was lower than expected at 83.6%, when compared to a prior large-scale United States based study in 2017 demonstrating 95.3% susceptibility. This finding of developing resistance is concerning. While WGS analysis of R isolates did not demonstrate clonality, it did show close relation. This data may suggest expansion of an emerging lineage, however more isolates will need to be studied for conclusion given limited sample size.

Disclosures
All Authors: No reported disclosures.
151. Molecular diversity and resistance mechanisms of Klebsiella pneumoniae bloodstream infections in Peru
Authors: Krapp Fiorella , Salvatierra Guillermo , Hinostroza Noemi , Garcia Coralith , Astocondor Aurora L , Ochoa Theresa , Jacobs Jan , Garner Omai , Nizet Victor , Tsukayama Pablo 
Published: December 2022

Abstract

Background
Klebsiella pneumoniae, a leading pathogen for mortality associated with antimicrobial resistance (AMR), was responsible for &gt; 250,000 deaths in 2019. Genomic surveillance can guide the development of vaccines and new antibiotics against this pathogen. While AMR disproportionally affects low-and middle-income countries, limited genomic data are available from these countries. To close this gap, this study provides genomic characterization of K. pneumoniae blood isolates recovered in Peru.

Methods
Consecutive non-duplicate K. pneumoniae blood culture isolates were collected during an AMR surveillance study (VIRAPERU) from Jul 2017 to Oct 2019, from 15 tertiary hospitals from 13 regions of Peru. DNA extraction (GeneJET, Thermo Fisher Scientific), DNA library (Nextera XT, Illumina) and genome sequencing (MiSeq 500bp-V2, Illumina) were conducted. De novo assembling (SPAdes v3.13.1), quality assessment and annotation (Nullarbor v2.0), and identification of species, ST group, K/O loci, AMR (Kleborate v2.0.1) were conducted. Phylogenetic trees were built with Microreact v.192.

Results
From 119 K. pneumoniae isolates, 114 were recovered and confirmed to belong to the Klebsiella taxon. Six species were identified, the most prevalent being K. pneumoniae (106), followed by K. quasipneumoniae (3). Among carbapenem-resistant isolates (n=13), 10 (77%) carried the blaNDM-1 gene, while other three carried blaKPC-2 (1), blaIMP-16 (1) or no carbapenemase (1). Phenotypic co-resistance to colistin was present in 2 isolates, both negative for mcr-1 gene. The most common mechanisms of resistance to 3rd generation cephalosporins, quinolones and to aminoglycosides were CTX-M-15 (74.4%), qnrB (63.6%), aac(6')-Ib-cr (87.5%), respectively. Many other AMR genetic determinants were identified (Fig. 1). Sixty ST groups were identified, but only 6 ST groups carried a carbapenemase gene (Fig. 2). A wide diversity of K and O locus was also identified (54 distinct K-loci and 14 distinct O-loci). Figure 1.Genetic determinants of antimicrobial resistance and virulence found in Klebsiella pneumoniae blood isolates of PeruFigure 2.Distribution of ST groups according to specific antimicrobial resistance profiles

Conclusion
Bloodstream infections in Peru are caused by a wide diversity of K. pneumoniae strains, carrying multiple AMR genes. Carbapenem resistance is principally a result of blaNDM-1 carriage, found across 6 specific ST groups.

Disclosures
Omai Garner, PhD, Beckman Coulter, Inc.: Clinical trial data collection funded by Beckman Coulter, Inc. Victor Nizet, MD, Cellics Therapeutics: Advisor/Consultant|Clarametyx Biosciences: Advisor/Consultant|Vaxcyte, Inc.: Advisor/Consultant|Vaxcyte, Inc.: Grant/Research Support.
154. Prevalence and Antimicrobial Resistance of Enterococcus species in a Tertiary Center Children’s Hospital in Korea
Authors: So Hyejin , Lee Jina 
Published: December 2022

Abstract

Background
Increasing prevalence of Enterococcus spp. as a nosocomial pathogen with high-level resistance to multiple antimicrobials has been a challenge throughout the years, and now, even to the pediatric age. This study is a pioneer research which was designed to determine the prevalence of different antibiogram patterns of enterococcal strains in the pediatric age.

Methods
In this retrospective review, we included Enterococcus species isolated from normal body fluid including blood and CSF from March 2014 through September 2020 at Asan Medical Center Children`s Hospital. Electronic Medical Records (EMR) was reviewed for clinical and demographic data.

Results
A total of 205 different clinical strains of Enterococcus species were collected. Isolated strains were E. faecalis (47.3%), E. faecium (41.5%), E. avium (4.9%), E. gallinarum (2.9%), E. raffinosus (2.0%) and others (1.5%). No strains were resistant to linezolid. Vancomycin or teicoplanin resistant strains were 26.3% (vancomycin 17.1%, teicoplanin 9.3%), most of which were E. faecium (vancomycin 13.7%, teicoplanin 9.3%). Ampicillin or penicillin resistant strains were 82.9% (ampicillin 39.0%, penicillin 43.9%), most of which were also E. faecium (ampicillin 35.1%, penicillin 36.1%). High-level streptomycin or gentamicin resistant strains were 46.8% (streptomycin 13.2%, gentamicin 33.7%), mostly E. faecalis (streptomycin 7.8%, gentamicin 19.0%). The prevalence of antimicrobial resistance differed significantly between E. faecalis and E. faecium; E. faecalis being nearly all susceptible to ampicillin and penicillin except 6 strains which was an interesting finding because ampicillin-susceptible, penicillin-resistant E. faecalis strains were found.
Antibiotic Resistance Pattern of Enterococcal Strains
MIC of ASPR Enterococcus species by Etest

Conclusion
Consistent findings with previous studies based on adults are that E. faecalis and E. faecium were the predominant strains causing infection in children as well. There are reports about currently emerging ampicillin-susceptible but penicillin-resistant(ASPR) E. faecalis strains which were also found in this study and so therefore further molecular studies about this newly emerging ASPR E. faecalis is in progress.

Disclosures
All Authors: No reported disclosures.