bluuebunny/crossref_metadata_2025 huggingface dataset:
2383. Immunogenicity and reactogenicity of a first booster with BNT162b2 or full-dose mRNA-1273: a randomised trial in adults ≥75 years (EU-COVAT-1) from the VACCELERATE consortium
Authors: Salmanton-Garcia Jon , Neuhann Julia M , Stemler Jannik , Carcas Antonio , Frías-Iniesta Jesús , Bethe Ullrich , Heringer Sarah , Tischmann Lea , Zarrouk Marouan , Cuepers Arnd , Koehler Philipp , Grothe Jan H , Singh Samir Kumar , García-León Alejandro , Loens Katherine , Lammens Christine , Koenig Franz , Yeghiazaryan Lusine , Posch Martin , Cornely Oliver A
Published: November 2023

Background

Vaccination remains crucial for protection against severe SARS-CoV-2 infection, especially in aged population.

Methods

We evaluated, with a randomised controlled, adaptive, multicentre phase II study, the safety and immunogenicity of a 3rd vaccination dose (1st booster) in individuals ≥75 years (ClinicalTrials.gov Identifier: NCT05160766, EudraCT Number: 2021-004526-29). Participants were randomized to either a full-dose (100µg) of mRNA-1273 (Spikevax®) or 30 µg of BNT162b2 (Comirnaty®). The primary endpoint was the rate of 2-fold antibody titre increase 14 days post-vaccination measured by quantitative enzyme-linked immunosorbent assay (Anti-RBD-ELISA). Secondary endpoints included changes in neutralising capacity (ACE2 Virus Neutralisation Assay) against wild-type and 25 variants at 14 days and up to 12 months.

Results

Fifty-three volunteers were randomised between 8 November 2021 and 4 January 2022, with 52 receiving a COVID-19 vaccine as 1st booster. Fifty subjects (BNT162b2 n=25/mRNA-1273 n=25) were included in the analyses for immunogenicity after day 14. The primary endpoint of a 2-fold anti-RBD IgG titre increase 14 days post-vaccination was reached in all subjects. A 3rd full-dose mRNA-1273 vaccination provided higher anti-RBD IgG titres (GMT D14 7090 [95% CI 5688 – 8837] BNT162b2 vs. 10711 [95% CI 8003 – 14336] mRNA-1273). A pattern showing higher neutralising capacity of full-dose mRNA-1273 against Wuhan wild-type so as for 23/25 tested variants was observed.

Conclusion

Third doses of either BNT162b2 or mRNA-1273 provide substantial antibody increase 14 days post-vaccination, with full-dose mRNA providing higher antibody levels and an overall similar safety profile for ≥75 subjects. Additional booster doses should be prioritised, particularly in aged people and others at high-risk. In-depth data on waning of immune response is needed to assess duration of protection, and evaluation of vaccine-dosage for individuals at risk may be reconsidered. With the data on full-dose (100µg) mRNA-1273evaluation of vaccine-dosage for individuals at risk may be reconsidered, despite the small sample size.

Disclosures

Jannik Stemler, -, Ministry of Education and Research (BMBF): Grant/Research Support Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds
2386. Examining Ways to Increase COVID-19 Vaccine Uptake through Motivational Interviewing
Authors: Reyes Summer M , Reyes Sydney A , Walsh Tyler , SHELLEY Jamee T , Agha Humza , Torres Ana V , Prater Jasmine , Smith Gabrielle D , Barksdale Nicholas , Lindsay Ryan R , Malone Sara , Newland Jason
Published: November 2023

Background

COVID-19 vaccine uptake in the U.S. has been poor especially among children. We are conducting a study evaluating 2 theoretically informed strategies to increase COVID-19 vaccine uptake.

Methods

A sequential multiple assignment randomized trail (SMART) design is being conducted where participants are randomized into receiving a text message with a link to COVID-19 vaccine resources or a motivational interview (MI). After 2 weeks, if the person is still not vaccinated, they are re-randomized to one of the same two strategies. Participants were eligible if they were completely unvaccinated or not up to date with their COVID-19 vaccines AND were a resident of St. Louis City or St. Louis County OR a school community member in one of our partnering school districts.

Results

171 individuals have participated in the trial. The median age was 28 (IQR 12-42) Of these, 107 were Black (63%), 44 White (26%), and 114 (67%) female (Table 1). 130 (76%) participants had received the flu vaccination before while only 42 (25%) had received at least one COVID-19 vaccine. A majority (65%) had private insurance; however, 3% had no insurance. Of those who received MI, the average response for importance (1= least, 10=most) of general vaccines and COVID-19 vaccines to one’s health was 7.86 and 4.06, respectively (Table 2). Ten was the most common response of participants for importance of general vaccines and 0 for importance of COVID-19 vaccines and readiness overall. Compared to COVID-19 vaccines, general vaccines had a higher importance overall and at intervention 1 and 2 time points (Figure 1a, b, & c). The four individuals received a COVID-19 vaccine during the study all received a MI call (3 had call as their only intervention while 1 had call then text).Table 1:Participant DemographicsTable 2:Motivational Interviewing Calls-Overall NumbersFigure 1:Average Numbers for MI Calls-Overall, First Intervention Only, and Second Intervention Only

Conclusion

General vaccines were regarded more highly than COVID-19 vaccines. With the continuation of this study as well as further analysis in participants’ reasons for their numerical responses, we can further understand why participants view these vaccines differently, what can be done to improve thoughts on COVID-19 vaccines, and increase COVID-19 vaccine uptake.

Disclosures

Jason Newland, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support
2391. Evaluation and Adjudication of Case Reports of Myocarditis After mRNA-1273 Vaccination
Authors: Urdaneta Veronica , Dharia Priyadarshani , Akangbe Oketoun , Laurent Samantha St , Esposito Daina , Emile-Backer Magalie , Straus Walter
Published: November 2023

Background

Myocarditis and/or pericarditis have been identified as very rare adverse events (AEs) associated with administration of COVID-19 vaccines, particularly mRNA vaccines. Cases were disproportionately reported in young men aged 18-24 years, within a few days after vaccination, mostly following a second dose. This analysis describes findings of the evaluation and adjudication of myocarditis/pericarditis AE reports (18 Dec 2020 – 17 Dec 2022) in the Moderna Global Safety Database (GSDB) following mRNA-1273 vaccination.

Methods

Two different case definitions were used to characterize level of diagnostic certainty and identify strength of evidence supporting a diagnosis of myocarditis/pericarditis: the Brighton Collaboration (BC) Case Definition (1-5 categories) and the Centers for Disease Control and Prevention (CDC) definition (probable/confirmed). Causality assessment was conducted using the standard WHO-UMC criteria. Based on epidemiological criteria, analysis was concentrated on reported cases involving individuals aged <40 years, including < 18 years, after >2 doses of mRNA-1273 and bivalent vaccines, regardless of the time-to-onset of AEs after vaccination.

Results

There were 6702 myocarditis/pericarditis cases after an estimated 773 million doses of mRNA-1273 (monovalent) or bivalent vaccine administered during the analysis period. There were no significant temporal changes in the demographic distribution of reported cases; 66.2% of these cases occurred in men aged 18-39 years (Figure 1) and after the second dose (28.3%). In individuals < 40 years of age, according to the BC, 38.1% of the cases were confirmed/probable; according to CDC definition 37% of the cases were confirmed/probable. WHO causality assessment indicated that 39.8% of the cases were probable/possible.

Figure 1

Percentage of mRNA-1273, mRNA-1273.214 (Original/BA.1) and mRNA-1273.222 (Original/ BA.4/5) Reported Cases of Myocarditis and Pericarditis by Age and Sex (18 December 2022 to 17 December 2022)

Conclusion

Adjudication of myocarditis/pericarditis cases following mRNA-1273 indicated that where information was available, most reports were Probable Cases, for both BC and CDC case definitions. According to WHO-UMC causality assessment most cases were considered possibly related to mRNA-1273.

Disclosures

Veronica Urdaneta, MD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Priyadarshani Dharia, PhD, MD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Oketoun Akangbe, PharmD, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Samantha St Laurent, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Daina Esposito, PhD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Magalie Emile-Backer, PharmD, CCRP, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds Walter Straus, MD, MPH, Moderna, Inc.: Salary|Moderna, Inc.: Stocks/Bonds
2401. The Role of Quantitative Microbial Cell-free DNA (mcfDNA) Sequencing (Seq) from Plasma in the Diagnosis (Dx) of Staphylococcal Cardiac Implantable Electronic Device Infective Endocarditis (CIED IE)
Authors: Karchmer Adolf W , Jenifer Kaufman M , Azim Ahmed Abdul , van den Berg Polly , Matos Jason D , Kramer Daniel B , Degner Nicholas R , Zimetbaum Peter
Published: November 2023

Background

Optimal treatment (rx) of staphylococcal CIED IE requires removing the entire CIED. Difficulty of dx plus cost and potential morbidity of rx make treatment challenging. Complicated staphylococcal bacteremia is associated with prolonged detection of plasma mcfDNA during antibiotic rx. To assess for IE, we studied plasma mcfDNA kinetics in CIED patients (pts) with staphylococcal bacteremia undergoing CIED removal.

Methods

With written consent, CIED pts (no persistent confounding infection) with bacteremia in the prior ≤ 7 days (d) and planned CIED removal had serial plasma specimens collected [Figure]. Quantitative mcfDNA-Seq was done using the Karius Test® at Karius CLIA certified Laboratory (Redwood City,CA) on batched pt specimens. Clinical data were obtained from the electronic medical record. CIEDs were removed through sterile pockets or surgically except in pt 012. Definite CIED IE was defined by multiple d of bacteremia plus a definite lead / tricuspid vegetation per echocardiogram, direct inspection or lead tip culture; multiple d bacteremia or a definite vegetation defined possible CIED IE.

Results

Nine pts with definite CIED IE had bacteremia 3-13 d (median 6 d) with Staphylococcus aureus (7 pts) or S. epidermidis (2 pts: 012 who due to retained lead fragment relapsed after rx 021) [Table 1]. At consent, after 2-11 d rx (median 6 d) mcfDNA was detected in 8 of 9 pts; in all 9, on CIED extraction mcfDNA increased significantly from consent and pre-extraction levels [Table3]. Five pts with possible S.aureus CIED IE had 1-3 d (median1 d) bacteremia [Table 2]. None had plasma mcfDNA after 5 d rx and 4 of 5 had no mcfDNA detectable on device extraction [Table3]. McfDNA patterns in definite CIED IE (8 of 9 pos on consent / pre-extraction and had an increase on extraction) differed from those in possible CIED IE (4 of 5 neg at 5 d of rx and none detected on extraction) [p=0.023 Fisher Exact].

Conclusion

Quantitative mcfDNA patterns can help distinguish definite from possible CIED IE and absence of mcfDNA in plasma of possible CIED IE on device extraction suggests that the CIED may not be infected. After 5 days of rx, plasma mcfDNA-Seq in CIED pts with staphylococcal bacteremia coupled with clinical features may identify patients that can be effectively treated without device removal - a testable hypothesis.

Disclosures

Adolf W. Karchmer, MD, DeBiopharma: Advisor/Consultant|DeBiopharma: Honoraria|Karius: Grant to Institution for this study Jason D. Matos, MD, Merck: Wife is an employee Nicholas R. Degner, MD, MPH, MS, Karius: Employer
2404. Widespread emergence of infective endocarditis due to Serratia spp.: Results of a large multicenter cohort
Authors: Madeline McCrary L , Shah Sunish , Slain Douglas , Stoner Bobbi Jo , Marx Ashley H , Schranz Asher J
Published: November 2023

Background

Infective endocarditis (IE) due to Serratia spp. (S-IE) has historically been considered a rare entity and limited to case series. Typically linked to injection drug use (IDU), S-IE appears to be growing amidst the opioid crisis. Guidance on therapy of non-HACEK gram negative IE remains limited. Our goal was to assess trends in S-IE and evaluate management strategies.

Methods

We retrospectively assessed adults treated for S-IE at 4 academic health systems in 4 US states from 2015-2021. Each site utilized different methods of identifying S-IE cases. Chart review was performed to assess management of cases. Multivariable logistic regression analyzed the association between antibiotic regimens and/or procedural management (defined as valve surgery or transcatheter aspiration of vegetation) with inpatient mortality (defined as inpatient death or hospice discharge) and was adjusted for select demographic and clinical factors (Table 2). Only the 3 sites with available antibiotic data were included in the adjusted model.

Results

169 cases of S-IE were identified with an overall increase from 2015 to 2021 and an apparent peak in 2019, although trends varied by site (Fig 1). 76% of cases were due to IDU, 56% involved a single left-sided valve and 40% were polymicrobial (Table 1). Inpatient mortality was 22%. 35% of patients had a procedural intervention, and 44% were treated with combination antibiotic therapy. Univariate analyses (Table 2) revealed significant associations between mortality and site of care, single left-sided valve disease, procedural management and treatment with combined beta-lactam and fluoroquinolone (BL+FQ). In the adjusted analysis, including 117 cases from 3 sites, lower inpatient mortality was associated with procedural intervention (OR 0.17, 95% CI 0.04-0.77) and BL+FQ treatment (OR 0.06, 95% CI 0.00-0.88).

Conclusion

In this large multicenter study, we found that S-IE is not infrequent, has high inpatient mortality and is treated with varying strategies. Procedural intervention and combination BL+FQ treatment were associated with lower mortality. Our study is limited by varying methods of case identification and a lack of data on clinical severity and surgical indications. Further study is urgently needed to define best management practices.

Disclosures

Asher J. Schranz, MD, MPH, WoltersKluwer: Honoraria
130. Influencing Antibiotic Prescribing for Patients with Enterobacter cloacae or Klebsiella aerogenes by Use of Templated Comments
Authors: Landolt Anna , Bennett Nicholas , Aragon Laura , Boyd Sarah E , Essmyer Cindy , Humphrey Matthew
Published: November 2023

Background

Antimicrobial resistance poses a significant threat in treating bacterial infections. One such concern is the treatment of AmpC beta-lactamase producing Enterobacterales. In October 2019, Saint Luke’s Health System incorporated an automated microbiology comment advising the avoidance of third generation cephalosporins in patients with cultures positive for two bacteria which most frequently express AmpC resistance: Enterobacter cloacae and Klebsiella aerogenes. We assessed the comments effect on treatment decisions and microbiologic outcomes.

Methods

This is a retrospective, pre-post, cohort study in a single health system. Patients were included if they were inpatients 18 years of age or older and had urine or blood cultures positive for E. cloacae or K. aerogenes. Patients were excluded if cultures were determined to be colonizing pathogens. Pre- (May to December 2018) and post-comment (May to December 2020) cohorts were compared to assess the influence of the comment on therapy selection and subsequent development of resistance. The primary endpoint was escalation to targeted antimicrobial therapy within the first 24 hours after culture speciation. Secondary outcomes included escalation within 72 hours of culture speciation, time to escalation, length of hospital stay, and subsequent development of multi-drug resistant organism one year following admission.

Results

Escalation of targeted antimicrobial therapy within 24 hours of culture speciation occurred in 20 patients in the pre-implementation group and 46 patients in the post-implementation group (p< 0.001). Escalation within 72 hours occurred in 34 patients in the pre-implementation group and 57 patients in the post-implementation group (p=0.004). Median time to change in antimicrobial therapy was 23 hours in the pre-implementation group and 7 hours in the post-implementation group (p< 0.001). There was no difference between groups in development of MDR (5 vs. 5.7%, p=0.6).

Conclusion

Implementation of templated microbiology comments increased the rate of escalation to targeted antimicrobial therapy in hospitalized patients with blood or urine cultures positive for E. cloacae or K. aerogenes. Templated comments are an effective, minimally invasive strategy to promote antimicrobial stewardship.

Disclosures

All Authors: No reported disclosures
2410. Clinical outcomes and antimicrobial management strategies of Pseudomonas endocarditis
Authors: Shah Sunish , Clarke Lloyd , Shields Ryan K
Published: November 2023

Background

Infective endocarditis secondary to Pseudomonas is rare. Our objective was to investigate outcomes of patients with Pseudomonas endocarditis by treatment strategy and identify factors associated with treatment failure.

Methods

Adult patients with definitive Pseudomonas endocarditis at 8 hospitals were identified between July 2010 and December 2022. Unless the cultured valve yielded a Gram-negative pathogen, patients with blood cultures growing Gram-positive bacteria or yeast for >24 hours were excluded. Combination therapy was defined as receipt of ≥2 in vitro active agents for ≥72 hours. Failure was a defined as death or microbiologic failure by day 42; microbiologic failures included escalation of antimicrobial therapy following treatment-emergent resistance, increased vegetation size, or blood cultures positive for ≥14 days.

Results

34 patients met the inclusion criteria. 32% (11/34) were people who inject drugs and 12% (4/34) were organ transplant recipients. P. aeruginosa was the underlying pathogen in 97% (33/34) of patients. 65% (22/34) and 35% (12/34) received combination and monotherapy, respectively. Patients managed with combination therapy had comparable rates of prosthetic valve endocarditis (41% vs 17%, P=0.25), a vegetation size > 1cm (59% vs 42%, P=0.33) and no receipt of cardiac surgical intervention despite an indication (32% vs 17%, P=0.44) compared to those who received monotherapy. There was no significant difference in 42-day failure rates (32% vs 17%, P=0.44), 90-day mortality (18% vs 25%, P=0.68) or median hospital length of stay (22 days vs. 23, P=0.914) between patients who receivedcombination therapy and monotherapy. Patients who experienced 42-day failure were more likely to have multi-drug resistant (MDR) Pseudomonas on initial blood cultures (44% vs 4%, P=0.012) and were less likely to be initially managed with piperacillin/tazobactam or cefepime (44% vs 96%, P=0.004) compared to those who experienced clinical cure.

Combination therapy versus monotherapy

Factors associated with clinical failure

Conclusion

To our knowledge, this is the largest study of Pseudomonas endocarditis to date. We did Not identify a benefit to combination therapy; however, the overall sample size was small. Endocarditis due to MDR P. aeruginosa was associated with a higher risk of clinical failure.

Disclosures

Ryan K. Shields, PharmD, MS, Allergan: Advisor/Consultant|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|Melinta: Grant/Research Support|Menarini: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Roche: Grant/Research Support|Shionogi: Advisor/Consultant|Shionogi: Grant/Research Support|Utility: Advisor/Consultant|Venatorx: Advisor/Consultant|Venatorx: Grant/Research Support
2413. Drug Use Associated vs Non-Drug Use Associated Endocarditis in an Academic Center from 2012-2017
Authors: Sobhanie Mohammad Mahdee , Clark Meagan J , Hebert Courtney , Haden Michael
Published: November 2023

Background

Drug use associated Infective Endocarditis (DU-IE) has been noted to be increasing over the last decade(Clinical Infectious Diseases® 2020;71(7):1664–7). In this study we sought to assess the unique aspects of DU-IE compared to IE not associated with drug use. We undertook an in-depth descriptive study of patients who presented with IE over the course of 5 years at one large academic medical center.

Table 1

Methods

This was a retrospective chart review of patients with IE admitted to the Ohio State Wexner Medical center between 2013 and 2017. Prisoners, patients < 18 or > 89 years of age, and pregnant patients were excluded from the study. The first admission during the study period in those with definitive or probable endocarditis by Duke criteria, were included. Persons who inject drugs (PWID) with IE were compared with those with IE without documentation of drug use. DU was determined by both ICD coding and manual chart review. Given the discrepancy between the two, chart review was used for the analysis. Differences in proportion were compared using Fisher’s exact, and continuous variables using student’s t-test.

Results

Overall, 713 patients met inclusion criteria. Approximately half (45.6%) of the patients had DU-IE, this proportion generally increased over the 5 years, with 59.8% of the cases being DU-IE in 2017. DU-IE patients were more likely to be younger, female, and have a lower Charlson comorbidity score. DU-IE patients were significantly more likely to have MRSA, Gram Negatives and Candida species, whereas non DU-IE was more likely to have Coagulase negative staph species. DU-IE patients were less likely to have a transesophageal echocardiogram, and unsurprisingly were more likely to have tricuspid valve involvement, and pulmonary septic emboli.

Conclusion

The patient population with DU-IE compared to non-DU IE differ from one another, and further studies are required to better understand long-term clinical outcomes in the treatment between each group.

Disclosures

All Authors: No reported disclosures
2418. Incidence and Characteristics of Midline-Associated Bloodstream Infections in an Urban Healthcare System
Authors: Choudhury Rebecca , Ehni Jordan , Rabinovitz Itay , Ekhelikar Nikita , Javaid Waleed , Camins Bernard , Jangda Mateen
Published: November 2023

Background

Midline catheters may carry a lower infection risk than central venous catheters, but available data is limited. Central line-associated bloodstream infection (CLABSI) incidence has increased during the COVID-19 pandemic, but is unclear what influence the pandemic has had on midline-associated bloodstream infections (MABSI). The objective of this study was to determine the incidence of MABSI during the COVID-19 pandemic and which pathogens were involved.

Methods

A health system infection prevention database was used to identify adult patients admitted to 6 acute care hospitals in 2021 who had a midline during admission and a positive blood culture. Cases were reviewed by a hospital epidemiologist and 3 supervised trainees for demographic data, microbiology data, and MABSI attribution using National Healthcare Safety Network (NHSN) CLABSI definitions.

Midline-Associated Bloodstream Infection Identification

Results

579 patients with possible MABSI were identified. 88 patients were determined to have a MABSI. 28 patients were excluded due to having a CLABSI-eligible central line at the time of the BSI. The remainder were excluded because the BSI did not fall within a MABSI eligibility period or because the BSI was secondary to another infection. MABSI and CLABSI rates for each hospital are shown in Table 1. MABSI occurred mostly in medicine patients (73, 82.95%). A slight majority of patients were male (48, 54.54%), and median age was 66 years (range 24-96). The most common organisms were Candida spp. (27), coagulase-negative Staphylococcus spp. (17), Enterococcus spp. (17), and Staphylococcus aureus (15). The 2021 yearly health system MABSI and CLABSI rates were similar (1.29 vs. 1.2), with variation between hospitals. Quarterly MABSI and CLABSI rates are shown in Figure 2. The health system MABSI rate appeared to increase during Winter 2021, while the CLABSI rate seemingly decreased.

MABSI and CLABSI Rates

MABSI and CLABSI rates by quarter of 2021. The blue line represents the MABSI rate, while the orange line represents the CLABSI rate.

Organisms isolated from blood cultures in MABSI patients. Gram positive bacteria were the most common isolates (57/123, 46.34%). More than 88 organisms were detected as many MABSI involved ≥2 possible pathogens (27/88, 30.68%).

Conclusion

In this study MABSI demographics were similar to those reported for CLABSI in other studies. While gram positive bacteria were common, as described in CLABSI, we also observed a high proportion of infections due to Candida spp. The health system MABSI rate was higher than the CLABSI rate, contrary to some studies. This was primarily driven by hospitals which were heavily impacted by the Omicron subvariant surge.

Disclosures

Bernard Camins, MD, MSc, Puro Lighting, LLC: Advisor/Consultant
2419. Increasing Misattribution of Bacteremia as CLABSIs by NHSN Definitions: A Tertiary Care Center Perspective
Authors: Ellsworth Misti G , Ausborn Valerie , Patel Bela , Chang Phillip , Ostrosky-Zeichner Luis
Published: November 2023

Background

The US has experienced a significant decrease in CLABSI rates over time but is stalling. NHSN has rigid definitions for secondary BSI attribution. We reviewed CLABSIs in a large tertiary acute care hospital to determine the frequency and trends of potential misattribution.

Methods

We reviewed 282 CLABSIs cases from 2019 to 2023 at a large tertiary hospital. A team of infection preventionists with high inter-rate reliability adjudicated each case strictly following NHSN methodology. A clinical review was performed by two hospital ID-trained epidemiologists to explore misattributed with an alternative primary infection.

Results

Of 282 CLABSI cases, 65% occurred in adults and 35% in children. 122 cases (43%) had a potential primary infection. The potential primary infections included: 33 (27%) pneumonia, 28 (23%) gastrointestinal infections, 6 (5%) urinary infections, 4 (3%) surgical infections, 13 (11%) skin and soft tissue infections, 11 (9%) vascular infections, 5 (4%) bacterial translocation, 8 (6.5%) infections that were present on admission, 4 (3%) CNS infections, 2 (1.6%) NEC infections, 2 (1.6%) musculoskeletal, 2 (1.6%) contaminates and 4 (3%) other non-NHSN specified sites. Pneumonia was the most frequent misattribution failing to meet imaging, laboratory, or documentation requirements within the infection window period (IWP). Intra-abdominal infection was the second most frequent cause of misattribution due to not meeting the imaging or matching site culture within the IWP. For the other categories, the most frequent reasons for not meeting the primary criteria included lack of matching culture, lack of clinical symptoms (often in intubated patients), or in the endocarditis category, the complexity of the criteria even with positive blood cultures and presence of vegetations. The graph shows an increasing proportion of misclassification over time.

Percent of Misattributed CLABSI by Fiscal Year

Conclusion

NHSN definitions and rules are becoming too prescriptive and may no longer be applicable to the complexity of cases, overestimating CLABSIs. As hospitals commit to CLABSI reduction, accurate and specific definitions are key in focusing efforts and attention and avoiding unfair penalties.

Disclosures

Luis Ostrosky-Zeichner, MD, FACP, FIDSA, FSHEA, FECMM, CMQ, Astellas: Grant/Research Support|Cidara: Advisor/Consultant|Cidara: Advisor/Consultant|F2G: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|GSK: Advisor/Consultant|Melinta: Advisor/Consultant|NIH: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Pulmocide: Grant/Research Support|Scynexis: Grant/Research Support|T2 Biosystems: Grant/Research Support|Viracor: Advisor/Consultant
131. Impact of an Algorithm to Triage Patients Discharged from the Emergency Department with Blood Cultures Positive for Staphylococcus aureus or Coagulase-negative Staphylococci
Authors: Brenneman Ethan , Theophanous Rebecca , Mando-Vandrick Jennifer , Toler Rachel , Jones Justin , Keil Elizabeth , Zhou Grace , Lee Hui-Jie , Moehring Rebekah W , Wrenn Rebekah
Published: November 2023

Background

Patients may be discharged from the emergency department (ED) prior to final data from blood cultures. When positive, the ED provider must evaluate to determine next steps in caring for the patient. Up to 55% of positive blood cultures can be contaminants, and calling patients back to the ED may cause undue burden to the ED if no treatment or further evaluation is needed. We developed a toolkit to assist provider response to positive blood cultures for Staphylococcus aureus and Coagulase-negative staphylococci (CoNS) in patients discharged from the ED. It identifies which patients need to return to the ED (callback) and which do not (likely contaminant).

Methods

We conducted a multi-center, retrospective cohort study of patients with positive blood cultures with staphylococci from January 2019 through October 2022 resulting after discharge from 3 EDs. The objective was to compare the rate of callback to the ED in a retrospective cohort to the rate guided by adhering to a newly developed callback algorithm. The rate of actual callback to ED and the rate of callback to ED based on adhering to the algorithm was calculated with 95% Wilson score binomial confidence intervals (CIs). Asymptotic McNemar’s test was used to compare the paired binomial proportions, and the difference in the rates was estimated with 95% CI using the Newcombe square-and-add approach.

Results

Out of 188 patients discharged from the ED with the growth of staphylococci in the blood cultures, the rate of patient callback was 61.2% (115/188, 95% CI 55.2% to 66.8%), compared to the algorithm advised callback rate of 45.7% (86/188, 95% CI 39.9% to 51.7%). The difference between the actual callback and the algorithm-based callback rates was 15.4% (95% CI 9.8% to 20.9%, p< 0.001).

Conclusion

Implementation of an algorithm-based response to blood cultures can reduce unnecessary callbacks to the ED without compromising patient safety.

Disclosures

Rebekah W. Moehring, MD, MPH, FIDSA, FSHEA, UpToDate, Inc.: Author Royalties
2422. Relative Risk of Patients Having a Catheter-Associated Urinary Tract Infection Within 7 days of Having an Indwelling Urinary Catheter Reinserted Within 24 Hours of Indwelling Urinary Catheter Removal
Authors: Hadhazy Eric , Shepard John , Graf Angela , Goor Joy , Buchake Bilwa , Lee Yohan , McIntyre Karen
Published: November 2023

Background

Indwelling urinary catheters (IUC) are reinserted in patients who should initially be managed with intermittent straight catheterization for urinary retention. We hypothesize patients who have an IUC reinserted within 24 hours will be at higher risk of catheter-associated urinary tract infections (CAUTI) within 7 days compared to patients who were straight catheterized or did not have an IUC reinserted.

Methods

A retrospective review of electronic health records (EHR) using Epic Systems (Verona, Wisconsin) was conducted for all inpatients at Stanford Hospital, Palo Alto, CA who had an IUC removed and a CAUTI defined by the National Healthcare Safety Network (NHSN) between January 1, 2020 to March 31, 2023. Patients with an IUC reinserted within 24 hours from initial removal of an IUC were compared to patients who had an IUC removed and did not have a reinsertion of an IUC within 24 hours. Relative risk of a CAUTI was the primary outcome metric.

Results

Between January 1, 2020 and March 31, 2023 there were 30,161 IUCs removed and 204 NHSN defined CAUTI identified within 7 days of removal that were included in the study. Patients who had an IUC reinserted within 24 hours had significant risk (RR: 7.96, p< 0.05) of having a CAUTI within 7 days post IUC removal compared to patients who did not have an IUC reinserted within 24 hours.Figure 1.Relative Risk of CAUTI with Indwelling Catheter Reinsertion

Conclusion

Reinsertion of IUCs in patients with urinary retention following IUC removal should be managed with intermitted straight catheterization or more conversative methods if possible. Patients who are re-catheterized with an IUC within 24 hours of removal are at significantly higher risk of developing a CAUTI within 7 days compared to patients who are straight catheterized or do not have a Foley catheter reinserted. Healthcare providers should use alternative methods of bladder management to improve patient outcomes.

Disclosures

All Authors: No reported disclosures
2423. Central venous catheter tip colonization and associated bloodstream infection in severe burn patients
Authors: Jeon Kibum , Han Seung Beom
Published: November 2023

Background

Because severe burn patients are at higher risk for catheter-related infections, routine changes of central venous catheters (CVCs) are commonly performed for them. However, there are limited information on pathogen colonization of the CVC tip and associated bloodstream infections (BSI) in burn patients.

Methods

In this study, medical records of severe burn patients, in whom routine CVC changes were performed every 7 days, were retrospectively reviewed. The results of CVC tip cultures and concurrently performed blood cultures were investigated.

Results

A total of 686 CVCs in 214 severe burn patients admitted to the burn intensive care unit were analyzed. A median of 2 CVCs (range: 1–15 CVCs) were inserted in each patient, and each CVC was maintained for a median of 8 days (range: 2–24 days). The median duration of catheterization was 17 days (range: 4–117 days). Of the 686 CVCs, 138 (20.1%) CVC tips were colonized by 150 pathogens (two pathogens in 12 CVCs), and 82 (59.4%) of them accompanied BSIs caused by the same pathogen. Non-flame burn (p < 0.001), higher total body surface area burn (p < 0.001), renal replacement therapy (p < 0.001), and femoral catheter (p < 0.001) were significantly associated with the development of catheter-related BSI in a multivariate analysis. Most cases of tip colonization (81.3%) and BSI (82.9%) were caused by Gram-negative bacteria: Acinetobacter baumannii and Klebsiella pneumoniae were most frequently identified.

Conclusion

Catheter-related BSI was accompanied in 12.0% of the changed CVCs: nine of ten CVCs might not require routine changing. Therefore, selective CVC changing at higher risk for catheter-related BSI seems to be appropriate rather than routine CVC changing in severe burn patients. Also, source control for burn wounds should be emphasized because most common pathogens of burn wound infection caused CVC tip colonization and BSI.

Disclosures

All Authors: No reported disclosures
2432. Antibiotic Lock Therapy as a Line Salvage Strategy for Catheter-Related Bloodstream Infections: A Retrospective analysis
Authors: Ranganath Nischal , Dumais Mitchell , Nair Vaisak , Tabaja Hussam , Stevens Ryan W W , O’Horo John C , Shah Aditya
Published: November 2023

Background

Catheter-related bloodstream infection (CRBSI) is an important complication of long-term central venous catheters (CVCs) and is associated with high morbidity and cost. While line removal is optimal, it is not always feasible and is not without complications. Antibiotic lock therapy (ALT) may be an alternative strategy for line salvage, but the efficacy of this approach particularly among immunocompromised hosts is unknown.

Methods

We retrospectively reviewed adult patients with CRBSI managed with ALT between 2018 and 2022 at our tertiary medical center. We reviewed patient comorbidities, type and indications for CVC use, microbiology of CRBSI, ALT, and use of systemic antibiotics. Outcomes included 30-day mortality, 90-day microbiologic relapse (with same bacteria as index case), 90-day recurrent BSI (with different bacteria from index case), and adverse events.

Results

86 patients were reviewed, a majority of whom were immunocompromised (91%) due to hematopoietic stem cell transplantation (85%) and thrombocytopenic (platelet count 36; IQR 17-112). 78% had tunneled CVC for indications including peri-transplant therapy (72%), chemotherapy (15%), and TPN (6%) (Table 1). The median time to CRBSI following CVC insertion was 45 days (IQR 19-86). Infections were frequently monomicrobial (80%) due to Gram-positive organisms (n=75) including coagulase-negative staphylococci and Enterococcus spp. The minority of Gram-negative (n=17) infections were due to E coli and Enterobacter spp. 94% of patients received systemic antibiotics and all patients received ALT for a median of 11 days [IQR 6-15] and 11.5 days [IQR 6-14], respectively (Table 2). The 30-day attributable mortality rate was low at 1%. Rates of 90-day microbiologic relapse (20%) and recurrent BSI (16%) were high, occurring at a median of 42 days (IQR 12-55) and 35 days (IQR 25-50) following completion of ALT, respectively (Table 3).

Conclusion

Despite high rates of microbiologic relapse and recurrent BSI, ALT may be an effective line salvage strategy extending the use of CVC by up to 30 days with minimal impact on mortality even among immunocompromised patients.

Disclosures

John C. O'Horo, Sr., MD, MPH, Janssen Pharmaceuticals.: Grant/Research Support|nference: Grant/Research Support
2433. Implementation of Midline Vascular Access Program and Reduction of Central Line-Associated Bloodstream Infections (CLABSI) in an Intensive Care Unit at a Community-Based Hospital
Authors: SAAD E L T A I B A , Meng Qingqing , Faris Mohammed , Stake Jonathan
Published: November 2023

Background

Central venous catheter (CVC) placement is the most frequently performed procedure in acute care hospitals for various indications in multiple clinical settings. CVCs are the main source of hospital-acquired bloodstream infections in the United States (US). Central line-associated bloodstream infections (CLABSIs) constitute a significant contributor to gross healthcare expenditure in the US health system. Reduction of the duration of the CVCs is a key factor to decrease the risk of CLABSI.

Methods

A retrospective study was conducted to compare the annual incidence of CLABSI rate, total CVC days, and device utilization ratio before and after the implementation of a midline vascular access program as an institutional-based intervention to reduce the CLABSI rate in the intensive care unit (ICU).

Results

The midline vascular access program was started in June 2021. Two study groups were compared (Group 1 includes the study period from January 2019 to June 2021 and Group 2 from July 2021 to December 2022). CLABSI number decreased from 22 to nine. The CLABSI rate (measured as CLABSI number per 1000 CVC days) decreased by 52% (6.8% o 3.3%) (P < 0.05) . There was a reduction in the total CVC days (3198 days in Group 1 vs 2731 days in Group 2) but it was not significantly associated with the decline in the CLABSI rate (P=0.0702). A 60% significant reduction rate was observed in the device utilization ratio (measured as total CVS days/ total patients’ days) (0.6 to 0.3) (P < 0.001), which was significantly associated with the decrease in the CLABSI rate (P< 0.001).Table 1.Results of study variables between the two study groupsFigure 1.The monthly number of CLABSI infections during the study period.

Conclusion

The midline vascular access program was associated with a reduction in the CLABSI rate per 1000 CVC days and the device utilization ratio in our ICU. The authors of this project are currently conducting a larger prospective case-control study to ascertain our preliminary study’s results which have some limitations attributed to its retrospective nature and sample size.

Disclosures

All Authors: No reported disclosures
2437. The Impact of Healthcare Associated Infections on Costs and Lengths of Stay 2019-2023
Authors: Sentiff Jennifer L , Yenugadhati Vamsi , Spitz Courtney , Glassman Shannon , Phillips Matthew , Frey Stephany , Lesho Emil P
Published: November 2023

Background

As 85% of hospitals in the U.S. face unsustainable operating margins, extraordinary labor costs (LC) from nursing shortages, and have under resourced infection prevention departments, updated assessments of the costs of healthcare associated infections (HAI) are needed. However, most published cost analyses are either more than a decade old, or did not adjust for timing of infection. We sought to determine excess lengths of stay (LOS) and LC associated with HAI during the COVID-19 era, while adjusting for timing of infection.

Timing of Infection Onset In Patients with an HAI

Legend: dark orange = days before infection; light orange = days after infection; yellow bar = geometric mean national average length of stay of uninfected patients with the same diagnosis code; green circle = mean length of stay of local uninfected controls

Methods

All inpatients in an academic tertiary care center and 4 community hospitals in Western NY from 01-01-19 to 12-31-22 were included. Using nationally standardized definitions of catheter-associated urinary tract (CAUTI), central line associated bloodstream (CLABSI), and surgical site infections (SSI), 728 HAIs were identified and compared to patients during the same encounter with the same diagnosis codes (DRG) without an HAI (n= 90,046). Only days after infection onset were used to calculate excess LOS and cost.

Results

The mean yearly standardized infection ratios (SIRs), as defined by the National Healthcare Safety Network, were 0.89, 0.98, and 1.14 for CLABSI, CAUTI and SSI, respectively. Patients with an HAI had significantly higher LC and longer post-infection LOS (all p-values < 0.005) compared to a national benchmark and their DRG-matched HAI-negative counterparts. Per admission, the average excess labor cost and excess LOS were $43,975, 13.4 days for CLABSI; $31,253, 8.9 days for CAUTI; and $5,985, 1.4 days for SSI (Table). The 4-year total was $23.4 M, and 4810 excess days. 100% of CLABSI and CAUTI occurred after the 13th day, and the pre and post-infection LOS were similar. SSI occurred early in admission, and the post-infection LOS was longer than the pre-infection LOS (Figure). Re-admission occurred for 83% of SSI. For CLABSI and CAUTI excess LOS and costs increased 178% over the study period.

Conclusion

These findings suggest that for CLABSI and CAUTI, minimizing pre-infection LOS can provide a greater economic and safety impact than focusing entirely on preventing the infection. However, for SSI, focusing on preventing the infection may provide the greatest benefit. Other hospitals can adjust these data based on their individual SIRs.

Disclosures

All Authors: No reported disclosures
2439. Excess Length of Stay and Mortality among the Critically Ill Adult Patients with Catheter-Associated Urinary Tract Infections in a Tertiary Care Teaching Hospital in Nepal
Authors: Shrestha Sailesh K
Published: November 2023

Background

Patients in the Intensive Care Units (ICU) with Catheter-associated Urinary tract infections (CAUTI) stay longer in the hospital and have excess mortality. Conventional techniques like matching designs or regression analyses to obtain these estimates are prone to time-dependent bias and bias due to competing events. Instead, a survival analysis technique called multistate modeling that describes the occurrence of events as transitions between multiple states over time, has been recommended. Reliable estimates of excess length of stay and mortality among patients with CAUTIs, using appropriate methodologies, have not been reported from Nepal. In this study, we examined the mortality and length of stay that could be attributed to CAUTIs in the ICU of our center.

Methods

We conducted this prospective cohort study in the 8-bedded medical ICU of a 458 bedded tertiary care teaching hospital in Kathmandu, Nepal. We included all the patients aged ≥ 16 years admitted to the medical ICU and with an indwelling urinary catheter for more than two calendar days during the one-year study period from June 2021 to July 2022. We diagnosed CAUTI using US CDC definitions and determined the antibiotic susceptibility of the bacteria when isolated. We summarized the categorical variables with frequency and numerical variables with median (interquartile range [IQR]). With the assumption of a constant hazard model, we used multistate models to calculate the transitional probabilities and estimate the excess length of stay and mortality.

Results

Of the 209 patients receiving urinary catheterization, more than half of them (120, 57.42%) were males and the median age was 50 (IQR 38 – 67.25) years. There were 32 (15.3%) CAUTI events identified. The urine samples of 25 patients yielded 27 microorganisms; 20 isolates among them were multi-drug resistant isolates. Escherichia coli was the most common microorganism. Overall, the patients with CAUTI stayed 2.5 days longer in the ICU and had 13% higher mortality than those without CAUTI.

Conclusion

The high burden of CAUTIs and the associated excess length of stay and mortality provide an approximation of the number of lives that could be saved and the number of bed days that could be gained by the appropriate CAUTI preventive and management strategies and should be reinforced.

Disclosures

All Authors: No reported disclosures
2440. Central Line-Associated Bloodstream Infection Incidence Reduction Accompanies Initial-Specimen Diversion Device Adoption
Authors: Stroupe Cody G
Published: November 2023

Background

Established lines are poor sites for sampling blood (frequently host to enterococci and Candida species) but peripheral venipuncture is an imperfect alternative as antiseptics struggle to eliminate deeply embedded microorganisms. State-of-the-art initial-specimen diversion device (ISDD) use can facilitate near-zero blood culture contamination rates, but impact on central line-associated bloodstream infection (CLABSI) incidence is unclear.

Methods

Intervention took place within a Joint Commission-accredited, 200-bed, acute-care community hospital serving nine Southeastern United States counties toward the objective of reduced CLABSI reporting. From September 2021 through March 2023, ISDD use augmented all peripheral venipuncture sample collection for adult patient blood culture. CLABSI reporting and the associated National Healthcare Safety Network (NHSN) standardized infection ratio (SIR) data for the 18-month intervention period was compared to the preceding 18-month period.

Results

For the 18 months prior to ISDD use, 6.5 CLABSIs were predicted and 17 CLABSIs were reported. For the 18 months during which ISDD use augmented standard procedure, 5.5 CLABSIs were predicted and 3 CLABSIs were reported. ISDD use accompanied an 80% reduction in SIR, from 2.6 to 0.5.

Conclusion

The study period coincided with the COVID-19 pandemic, a nationwide struggle with considerable quality control shortcomings observed in this space that, by juxtaposition, reinforce the strengths of the intervention. SIRs are the primary means of tracking healthcare-associated infection trends, and financial penalties follow performances failing to meet predictions. As CLABSI reporting throughout the intervention period was dramatically below NHSN prediction, the author concludes that ISDDs have standard-of-care potential and encourages further study in the interest of antimicrobial stewardship and quality control.

Disclosures

All Authors: No reported disclosures