bluuebunny/crossref_metadata_2025 huggingface dataset:
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

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

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 > 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 < 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

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

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 < 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

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

Background

Klebsiella pneumoniae, a leading pathogen for mortality associated with antimicrobial resistance (AMR), was responsible for > 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

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.
161. Assessing Trends in 1,3-β-D Glucan and Aspergillus Galactomannan Antigen Ordering to Improve Use
Authors: Poplin Victoria , Liesman Rachael , Bahr Nathan C
Published: December 2022

Background

1,3-β-D Glucan (BDG) and Aspergillus galactomannan antigen (GM) are commonly ordered. Overutilization of these tests increases the incidence of false positive results, potentially leading to unnecessary follow up testing, procedures, and treatment. The aim of this quality improvement (QI) study was to improve our understanding of BDG and GM utilization at our institution.

Methods

The test orders for BDG and GM were modified within our electronic medical record (EMR) to provide education and require selection of ordering reason from a list of criteria. Educational sessions were provided to non-transplant provider groups who order BDG and GM frequently. Total number of tests, test results, patient immunosuppressed status, ordering location, and provider specialty were compared for a 3-month period pre/post intervention. Ordering criteria was collected post-intervention. SPSS software was used for chi square tests comparing groups.

Results

BDG and GM ordering practices were compared in the pre- and post-intervention timeframes (Table 1). There were no significant differences in the total number of tests, immune status of patients, ordering location or test results for BDG or GM. A significant decrease in hospitalist ordering was found (n=79 (pre), n=48 (post), p=0.006). Positive GM tests were rare in both periods (1.96%, 6/306 and 3.34%, 10/299). Ordering criteria for both tests were also evaluated in the post-intervention period (Table 2). The most common ordering criteria selected for BDG and GM were disseminated fungal infection 275/435 (63%) and invasive aspergillosis 241/299 (81%), respectively.

Conclusion

Most BDG and GM tests were ordered utilizing appropriate ordering criteria and were among immunosuppressed patients. However, selection of an appropriate reason does not necessarily correlate to obtaining in the appropriate clinical setting. This QI project improved our understanding of how BDG and GM are utilized, and by whom. In the future, these results will be used to provide more targeted education to specific provider groups. In addition, further EMR order entry modifications will focus on potential false positive results to further optimize BDG and GM test utilization.

Disclosures

All Authors: No reported disclosures.
162. Assessment of Guideline-Concordant Testing for Legionella pneumophila and Streptococcus pneumoniae in Community-Acquired Pneumonia
Authors: Malik Waleed , Fisher Ann , Kotansky Brian , Dembry Louise , Datta Rupak
Published: December 2022

Background

Urinary antigen testing for Streptococcus pneumoniae and Legionella pneumophila is only recommended in patients with severe pneumonia according to the 2019 guidelines from the American Thoracic Society (ATS) and Infectious Diseases Society of America (IDSA). Unnecessary testing for these organisms may increase antibiotic utilization. This quality improvement project evaluated whether patients who received a Streptococcus pneumoniae or Legionella pneumophila urine antigen met criteria for testing.

Methods

We conducted a cohort study of patients who received a urinary antigen test for Streptococcus pneumoniae or Legionella pneumophila within 3 days of admission to the Veterans Affairs Connecticut Healthcare System between September 1, 2018 and September 1, 2021. We determined whether patients had clinically defined pneumonia per National Healthcare Safety Network criteria. Among patients that met criteria for clinically defined pneumonia, the subset with severe pneumonia according to the ATS/IDSA guidelines was identified. We used the ATS/IDSA guidelines to determine whether patients received guideline-concordant choice of therapy.

Results

We identified 352 patients who received a urinary antigen test within 3 days of admission. Mean age was 72.6 years, 97% (n=278) were male sex, and 86% (n=301) were White race. Common comorbidities included heart disease (76%, n=268), lung disease (58%, n=203), and diabetes (30%, n=106). Overall, 36% (n=127) of patients met criteria for clinically defined pneumonia, and 7% (n=25) met criteria for severe pneumonia. 9 patients had a positive Streptococcus pneumoniae antigen test and 1 patient had a positive test for Legionella. Among patients with clinically defined pneumonia, 74% (n=75) received guideline-concordant choice of therapy and 74% (n=75) received an antibiotic duration >5 days

Diagnostic and Therapeutic Characteristics of Veterans According to Presence of Pneumonia

Conclusion

Only 7% of patients who underwent urine antigen testing for Streptococcus pneumoniae or Legionella pneumophila met criteria for testing per ATS/IDSA guidelines, and length of therapy was prolonged in the vast majority of patients. These data support the need for a clinical decision-making tool to reduce unnecessary testing and treatment for pneumonia at our institution.

Disclosures

All Authors: No reported disclosures.
164. BioFire FilmArray Pneumonia Panel Implementation: Examining Appropriate Usage and Opportunities for Diagnostic Stewardship
Authors: Zelus Casey S , Van Schooneveld Trevor C
Published: December 2022

Background

The BioFire FilmArray Pneumonia Panel (PnaP) is a novel diagnostic tool for rapid diagnosis of lower respiratory tract infections. However, appropriate usage and optimal implementation strategy in the clinical setting remain poorly characterized. The PnaP assay was introduced along with institutional guidance restricting use to intensive care units (ICUs) and Infectious Disease and Pulmonary consultative services. Examining guideline compliance and clinically appropriate PnaP usage highlights the role of diagnostic stewardship in improving management of pneumonia in hospitalized patients.

Methods

PnaP testing was obtained retrospectively from hospitalized adults over a 6-month period (January 1 - June 30, 2021). Outpatient and pediatric (< 18 years of age) testing was excluded. Appropriate use criteria based on institutional guidance are defined in Figure 1. Primary outcomes included PnaP results with respect to utilization appropriateness. Statistical analyses included chi squared testing with p-value < 0.05 considered statistically significant.

Results

PnaP testing was performed on 574 respiratory samples from 440 patients (Table 1). Overall compliance with institutional guidance was 84% (n=482/574) but varied with respect to level of care (ICU 89% vs non-ICU 72%, p < 0.001) and location (Table 2). Repeated testing was the most common reason for non-compliance, accounting for 59% of inappropriate use. Positivity rates varied significantly respect to guideline compliance and level of care, with distinct pathogen isolation profiles seen among ICU and non-ICU patients. Pathogen isolations was not significantly impacted by respiratory sample type (Table 3).

Conclusion

Multiplex panels can isolate significant more pathogens compared to traditional diagnostic testing, with the potential to identify additional variables that factor into pneumonia pathology. PnaP assay results and appropriateness of use appear intertwined, with criteria compliance significantly impacting positivity rates, with distinct pathogens isolated among ICU and non-ICU patient groups. Our study highlights specific target areas for intervention, with the potential to promote clinically appropriate diagnostic testing by adjusting ordering restrictions at our hospital.

Disclosures

Trevor C. Van Schooneveld, MD, bioMerieux: Advisor/Consultant|bioMerieux: Grant/Research Support|Insmed: Grant/Research Support|Merck: Grant/Research Support|Thermo-Fischer: Advisor/Consultant.
166. Bring your boots: wading through GI PCR panel diagnostic stewardship applications
Authors: Bennett Nicholas , Boyd Sarah E , Sattler Jeffrey , Boos Ginny , Johnston Cara , Humphrey Matt , Aragon Laura , Aragon Laura , Essmyer Cynthia
Published: December 2022

Background

Infectious diarrhea is a common cause of emergency department (ED) visits and hospital admissions. Polymerase chain reaction (PCR) testing allows for quick and expansive pathogen identification and facilitates earlier targeted treatment. We implemented a multiplex gastrointestinal (GI) PCR panel in 2014. In collaboration with the Antimicrobial and Diagnostic Advisement Program (ADAP), post-launch optimization strategies have changed test use. We evaluate the impact of diagnostic stewardship initiatives.

Methods

GI PCR testing was initially unrestricted for ED or inpatients within 72 hours of admission. After fielding many questions regarding interpretation, the ADAP developed a guidance document in June 2019 regarding treatment considerations for all potential organisms detected. In January 2020, organism-specific treatment considerations were embedded in the test results real-time treatment guidance (figure 1). A pre-post quality improvement assessment of the changes was performed. In August 2021, individual GI PCR panel orders were replaced with an order set containing a decision tree to provide passive guidance evaluating acute vs chronic diarrhea, assessing recent antibiotic use (to consider C. difficile testing), no testing scenarios, and avoiding repeat testing (figure 2). Figure 1Example of templated comments for Norovirus embedded within GI PCR panel results.

Figure 2 GI PCR panel order set

Results

GI PCR panel use peaked in 2019 with 3,142 tests processed. The guidance document was less helpful, requiring an external site link. Embedding organism-specific GI PCR guidance significantly improved appropriate antibiotic prescribing (77.9 vs 89.1%, p=0.001). A precipitous drop off in GI PCR test orders occurred after the COVID-19 pandemic began (1,774 in 2020), partly attributed to supply chain issues. When comparing intra-pandemic years (2020 vs 2021), implementation of a smart order set was associated with a 51.3% reduction in orders (1,774 vs 864) and $131,000 in savings despite significant patient volume increases in 2021. Low use rates have persisted into the first quarter of 2022 (n=229).

Conclusion

Diagnostic stewardship changes should be proactive and contextually relevant at the time of result interpretation. Antimicrobial stewardship programs are uniquely positioned to lead optimization initiatives and drive clinical and cost-effective solutions.

Disclosures

All Authors: No reported disclosures.
170. Comparison of Traditional Stool Culture and Targeted Testing Using Multiplex PCR to Diagnose Infectious Diarrhea at the Atlanta VA Medical Center (AVAMC): A Diagnostic Stewardship Initiative.
Authors: Molinari Alexander H , Epstein Lauren H , Darius Nicole , Goolsby Tiffany , Webster Andrew S
Published: December 2022

Background

Multiplex PCR panels have become common for diagnosing infectious diarrhea; however, indiscriminate use of multiplex PCR panels may identify common pathogens that do not require treatment.

To optimize laboratory workflow and improve diagnostic stewardship, we developed a targeted algorithm to optimize multiplex PCR testing at the AVAMC. We retroactively applied the targeted algorithm to historical stool cultures to assess the potential impact on diagnosis, inappropriate test ordering, and cost. Figure 1Targeted Algorithm for Testing Infectious Diarrhea

Methods

In March 2022, multiplex PCR testing (Biofire) was initiated at AVAMC; we developed a targeted algorithm to inform testing of patients at highest risk from infectious bacterial diarrhea (Figure 1). We retrospectively reviewed all clinical information among patients with bacterial stool testing, which included cultures and antigen tests, obtained from January 1, 2019 to December 31, 2021. In our analysis, we included all patients with a positive stool culture and a random sample of patients with a negative stool culture. We applied the targeted algorithm to both retrospective cohorts in order to evaluate potentially missed cases, outcomes, and overall differences in costs and labor between traditional stool cultures and targeted multiplex PCR testing.

Results

We identified 1027 patients with bacterial stool testing. Among 27 patients with a positive stool test, the targeted algorithm missed testing among 6 (22%) patients with mild, self-limited disease that resolved within 7 days. Among 100 patients with negative stool cultures, the targeted algorithm excluded testing among 75 (75%) patients. Among the remaining 25 (25%) negative patients who would have been tested using the targeted algorithm, 14 (56%) were high-risk and 16 (64%) had severe illness. Eliminating unnecessary stool testing using a targeted algorithm would have saved an estimated $50,000 and 750 laboratory labor hours.

Conclusion

At our facility, the implementation of algorithm-guided infectious diarrhea testing by multiplex PCR is estimated to reduce laboratory time and materials costs while eliminating 75% of unnecessary testing. Algorithm-guided testing would capture the majority of bacterial diarrhea at our institution but could lead to missed diagnoses in lower-risk populations.

Disclosures

All Authors: No reported disclosures.
176. Evaluation of the Predictive Value of Methicillin-Resistant Staphylococcus aureus (MRSA) Nares Polymerase Chain Reaction (PCR) Screening within Hospitalized Patients
Authors: Alilaen Nicole , Vu Catherine , Burke Victoria , Bellfi Lillian
Published: December 2022

Background

While MRSA nares PCR screening utilization has established evidence for de-escalation of anti-MRSA agents in pneumonia, its utility in other sites of infection is not well studied. The purpose of this study was to evaluate the utility of MRSA nares PCR screening within a wide range clinical specimens and its impact on antimicrobial stewardship.

Methods

This retrospective study was conducted at a 446-bed academic medical center. Patients ≥ 18 years old with an in-house MRSA nares PCR ordered between 1 November 2021 and 1 February 2022 were included in the primary analysis. Negative predictive value (NPV), positive predictive value (PPV), sensitivity, and specificity were calculated using cultures obtained within 7 days of nares screening. Vancomycin duration, de-escalation, and incidence of acute kidney injury were collected pre- and post- implementation of the in-house MRSA PCR screening. The pre-intervention cohort observed patients admitted from 1 November 2020 to 1 February 2021 screened by send out MRSA nares PCR.

Results

At baseline, patients were a mean age of 55 years old, 55% black, and required ICU care in 50% of cases. A total of 665 cultures from 308 patients were included in the primary analysis (131 respiratory, 282 blood, 154 urine, 61 wound, 22 sterile fluid, 15 bone, and 12 spinal fluid specimens). The overall NPV of the MRSA nares PCR screening was 99.8% and the PPV was 21.1%. The sensitivity and specificity were 96.8% and 81.67%, respectively. Duration of vancomycin was a median of 3 days in both the pre- and post- intervention cohorts. However, rates of vancomycin de-escalation increased at day 3 from 31.5% to 48.1% and at day 5 from 69.9% to 80.0% post implementation on an in-house MRSA PCR screening. Incidence of acute kidney injury decreased from 45.2% to 21.6%.

Conclusion

Based on its high NPV among cultures of different sites, MRSA nares PCR screening may be utilized to de-escalate anti-MRSA agents within tertiary care facilities.

Disclosures

All Authors: No reported disclosures.
185. Implementation of Multiplex Polymerase Chain Reaction in Clinical Practice: Impact on Antimicrobial Management In Infectious Diarrhea
Authors: Kelly Gillean , Iordanov Roumen , Franklin Alex , Ahmed Amna , Srinivasan Krithia , Hayon Jesica , Lasco Todd M , Amini Rosie , Shay Sabra , Kulkarni Prathit A , Mohajer Mayar Al
Published: December 2022

Background

Stool culture and stool polymerase chain reaction (PCR) panels are both used to evaluate patients with suspected infectious diarrhea. Stool PCR panels are especially advantageous because of their ability to detect a broad array of infectious pathogens in less than one hour. Our study assessed how the use of stool PCR panels instead of stool culture impacted antibiotic days of therapy (DOT) and length of therapy (LOT) in hospitalized patients with suspected infectious diarrhea.

Methods

In December 2021, an intervention was implemented in our hospital in which all electronic orders for stool cultures were automatically switched to stool PCR testing. The pre-intervention group was comprised of 75 hospitalized adult patients who had a stool culture obtained from September to November 2021. The post-intervention group was comprised of 81 adult patients who had a stool PCR obtained from December 2021 to February 2022. The DOT and LOT for antibiotics prescribed specifically for infectious diarrhea were determined for each patient; DOT and LOT were compared between the pre- and post- intervention groups.

Results

The median DOT in the pre- and post-intervention groups was 0 with a range of 0-10 and 0-8, respectively. The median LOT in the pre- and post-intervention groups was 0 (range 0-5 for both groups). No significant difference in the median DOT (Wilcoxon rank sum test, p-value = 0.967) or LOT (Wilcoxon rank sum test, p-value = 0.993) was found between the pre- and post-intervention groups (Figure 1). After adjusting for patient days present, no significant change in DOT or LOT incidence rate was found between the pre- and post-intervention groups. The DOT incidence rate ratio (RR) was 0.71 (95% CI 0.42, 1.22), and the LOT incidence RR was 0.67 (95% CI 0.36, 1.24). Figure 1.DOT and LOT Comparisons between Pre- and Post-Intervention Groups

Antibiotic days of therapy (DOT) stratified by study period (top) and antibiotic (LOT) stratified by study period (bottom).

Conclusion

An intervention of automatically changing stool culture testing to stool PCR testing did not result in a significant change in median DOT or LOT in hospitalized adult patients, nor did it result in a significant change in DOT or LOT incidence rate. These findings could be explained by an insufficient sample size (n = 156), limiting the study’s power. Additionally, most patients in the pre-intervention group received no antibiotics for infectious diarrhea, resulting in a short DOT and LOT at baseline.

Disclosures

Sabra Shay, BSN, MPH, Premier Inc.: Employee Prathit A. Kulkarni, M.D., Vessel Health, Inc.: Grant/Research Support.
188. Opportunities for antimicrobial stewardship: Time to optimal therapy and vancomycin use in gram-positive and contaminated blood cultures before and after implementation of rapid blood culture diagnostic testing
Authors: Olion Kelsey , Hamann Laura , Jennemann Rebecca , Shapiro-Schere Julie A , Burnett Yvonne J
Published: December 2022

Background

Rapid molecular diagnostic tests improve time to organism identification and may expedite antimicrobial de-escalation. Through faster detection of contaminated samples, rapid blood culture identification (BCID) should also reduce unnecessary antibiotic use. BioFire FilmArray BCID was implemented in July 2019 at a community hospital. This study compared antimicrobial use for gram-positive blood cultures before and after BCID implementation to identify areas for further antimicrobial stewardship intervention.

Methods

This retrospective cohort study evaluated adult patients at a 450-bed community hospital with gram-positive blood culture results between February and June 2018 and 2019 (pre-and post-BCID). Patients were excluded for polymicrobial bacteremia, pregnancy, or expiration/hospice status before blood culture positivity. The primary outcome was time to optimal therapy (TTOT) for bacteremia, defined as time to antimicrobial de-escalation, discontinuation, or result for untreated contaminated cultures. Time to organism identification, receipt of optimal therapy, and vancomycin duration were also evaluated, in addition to subgroup analysis of contaminated cultures (identified by microbiology comment or physician note).

Results

Of the 232 patients, median age was 70 years and 54.3% were male. Coagulase-negative staphylococci was most commonly isolated (n=104, 45%) and contamination rate was 53.4%. Median TTOT improved from 53.3 vs 28 hours, p< 0.001 in pre- vs post-groups, respectively, and optimal therapy selection increased from 83% to 93%, p=0.028. Median time to organism identification was 60.2 vs 23.5 hours, p< 0.001. Median duration for vancomycin (35.1 vs 25.2 hours, p=0.231) and overall antimicrobial duration did not differ between groups. Among contaminated blood cultures, TTOT improved (54 vs 27.3 hours, p< 0.001) and vancomycin median duration decreased (27.5 vs 16.6 hours, p=0.253).

Conclusion

Rapid BCID significantly improved TTOT, resulting in improved rates of optimal therapy and an observed reduced vancomycin duration. High rates of contaminated blood cultures identified opportunities for coordination with antimicrobial stewardship to reduce contamination rates and improve antimicrobial use.

Disclosures

All Authors: No reported disclosures.
192. Predictors of Actionable Results on Gastrointestinal Panel Testing for Children Hospitalized with Acute Diarrheal Illnesses
Authors: Ho Erin , Dominguez Samuel R , Cotter Jillian , Thomas Jacob
Published: December 2022

Background

Among hospitalized children with acute diarrheal illnesses, multiplex PCR gastrointestinal panels (GIP) are commonly overused. GIPs are most likely to impact management and outcomes if an actionable (bacterial or parasitic) result is obtained. To inform future diagnostic stewardship, we evaluated which clinical factors, including provider-reported test indications and stool frequency, were associated with actionable results.

Methods

This is a multicenter cross-sectional study of children ≤ 18 years old hospitalized at any Children’s Hospital Colorado site between 2015-2018 with a diarrheal illness and at least one GIP performed. We used multivariable logistic regression to determine associations between actionable GIP results and testing indication, stool frequency, and demographics. We evaluated these findings in two subgroups - patients with at least one complex chronic condition (CCC) and non-CCC patients.

Results

There were 1,124 GIPs performed for 967 encounters. Yield of actionable results was higher for non-CCC than CCC patients (30% vs. 21%, p < .001) (Image 1), and test indications differed between the two groups (Table 1). For non-CCC patients, we found positive associations between actionable results and “Diarrhea with blood or pus” test indication (relative risk (RR) 1.5, confidence limits (CL) 1.09-2.07, p = .01), summer season (RR 1.69, CL 1.14-2.5, p =.01), and age ≥1 yr (RR 2.88, CL 1.82-4.54, p< .001). Male gender was negatively associated (RR 0.75, CL 0.58-0.96, p=.02). For CCC patients, age ≥1 yr was positively associated with actionable results (RR 3.17, CL 1.59-6.32, p = .001). ≥4 stools per day (RR 0.73, CL 0.54-.99, p=0.04) and ICU admission (RR 0.69, CL 0.5-0.95, p=0.2) were negatively associated with actionable results (Table 2).

Conclusion

For both cohorts, age ≥1 was positively associated with actionable GIP results. For otherwise healthy children, bloody diarrhea and summertime were positively associated with actionable results. CCC patients had less frequent actionable results, and no GIP indications were predictive of actionable results. A higher stool burden did not statistically increase the probability of an actionable result in either cohort. These results may guide diagnostic stewardships efforts for GIP ordering in pediatric patients.

Disclosures

Samuel R. Dominguez, MD PhD, Biofire DIagnostics: Advisor/Consultant|Biofire DIagnostics: Grant/Research Support|DiaSorin Molecular: Advisor/Consultant|Karius: Advisor/Consultant|Pfizer: Grant/Research Support.
205. IL-1 β gene (+3954C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms associate with early aseptic loosening of hip and knee arthroplasties but not with implants infection
Authors: Lopez-Anglada Esteban , Collazos Julio , Montes Angel Hugo , Perez-Is Laura , Perez-Hevia Imanol , Jimenez-Tostado Sergio , Suarez-Zarracina Tomas , Alvarez Victoria , Valle-Garay Eulalia , Asensi Victor
Published: December 2022

Background

Aseptic prosthetic loosening (APL) and prosthetic joint infections (PJI) are frequent complications of hip and knee implants. Polymorphisms of cytokines and nitric oxide (NO), key inflammatory molecules in APL and PJI pathogenesis, could explain individual susceptibility to these complications.

Methods

Three cytokines (IL-1-a, IL-1-β, TNF-α) and two nitric oxide synthase (NOS2, NOS3) genes polymorphisms were genotyped in 77 APL and 117 PJI patients and 145 controls with aseptic hip or knee implants lasting > 16 years. Plasma cytokines and nitrate-nitrite (NOx) levels were measured.

Results

The TT genotype and T allele of the (+3954C/T, exon 5, rs1143634) IL-1β polymorphism were more frequent in APL patients compared to controls (p=0.03 and p=0.02, respectively). No genotypic associations in PJI patients were observed. S. epidermidis was their most frequently isolated microorganism (39.3%). Plasma IL-6, TNF-α and NOx were significantly different between APL and controls (p< 0.0001). Plasma IL-1β and IL-6 were significantly higher in APL T allele carriers vs. non-carriers (p< 0.03). Knee implant (HR 2.488, 95% CI 1.307-4.739, p=0.005), male gender (HR 2.252, 95% CI 1.121-4.525, p=0.023), carriages of the TT genotype of the (+3954C/T) IL-1β polymorphism (HR 3.704, 95% CI 1.274-10.753, p=0.016) and AA genotype of the (exon 22) NOS2 polymorphism (HR 3.509, 95% CI 1.266-9.709, p=0.016) were independently associated with a shorter implant survival by Cox regression.

Conclusion

Genotyping of IL-1β (+3954C/T, exon 5, rs1143634) and NOS2 (exon 22) polymorphisms could be useful as predictors of early hip or knee APL.

Disclosures

All Authors: No reported disclosures.
228. Infection Control Cluster Randomized Control Trials and Healthcare Facility Participation: A Need for Readiness Assessment
Authors: Ray Cara E , McKinley Linda , Keating Julie , Baubie Kelsey , Safdar Nasia
Published: December 2022

Background

Validated tools to evaluate organizational readiness exist within the implementation science literature, but readiness assessments for healthcare organization participation in cluster randomized control trials (CRCTs) have not been developed. CRCTs have been important for increasing the evidence base for infection control. This study describes complex contextual factors that can impact participation in a multi-site infection control CRCTs within the VA healthcare system.

Methods

To assess study participation eligibility and feasibility, a survey of ten inpatient acute care patient units within five VA healthcare facilities was conducted to evaluate standard eligibility criteria such as facility and patient unit demographics, infection rates, and letters of support from leadership. With study delays we began conducting readiness evaluations through email communications and conference calls. We identified several metrics of readiness including competing priorities, identification of champions/ stakeholder engagement, and research infrastructure.

Results

Our Initial survey metrics received from facilities interested in study participation were efficient in detecting study eligibility but lacked efficiency to detect study feasibility. Later metrics identified barriers to feasible study implementation (i.e., readiness), primarily competing priorities, specifically due to the pandemic. Other barriers included the lack of research infrastructure and lack of champion identification/stakeholder engagement. These contextual factors were generally elicited through ongoing communication rather than from the initial survey assessment.

Conclusion

Organizational readiness can delay or impede important infection control CRCTs. This study exemplifies the complexity of healthcare organizations participation in clinical studies that may not be addressed in existing readiness tools or assessments. The emergence of the covid pandemic amplified the importance of identifying a wide range of contextual factors that need to be captured in ongoing assessments for readiness. An essential first step in developing organizational readiness tools and assessments is to identify and define readiness constructs in complex changing healthcare settings.

Disclosures

All Authors: No reported disclosures.