bluuebunny/crossref_metadata_2025 huggingface dataset:
2267. Evaluation of Antibiotic Prescribing Trends from a Dental Clinic After Implementation of a Dental Antimicrobial Stewardship Initiative
Authors: Njeim Noor M , Stilwell Allison , Horowitz Harold , Brandwein Aaron , Sconzo James , Droumbakis Claire
Published: November 2023

Background

Inappropriate antibiotic prescribing by dentists is as high as 80% and in the U.S., dentists rank third for writing the most antibiotic prescriptions. At NewYork-Presbyterian Brooklyn Methodist (NYP-BMH), the Antimicrobial Stewardship Program (ASP) and Division of Dental Medicine collaborated to create a clinical practice guideline regarding antibiotic use in dentistry that was implemented in May 2021 and is reinforced with annual education to dental prescribers. The purpose of this study is to compare outpatient antibiotic prescribing trends pre- and post-guideline implementation.

Methods

Patients presenting to NYP-BMH dental clinic for an emergent indication and prescribed an antibiotic from January-April of 2019-2021 (pre) and January-April of 2022 (post) were included. The primary outcome was appropriateness of antibiotic therapy. Secondary outcomes included a comparison of antibiotic selection, dosing and duration of therapy. A subgroup analysis of patients with reported penicillin allergies was conducted to compare alternative agents prescribed.

Results

A total of 119 patients in the pre and 100 patients in the post-guideline period were included. The primary outcome of appropriate antibiotic prescriptions significantly improved after guideline implementation (pre 45% vs post 64%, p< 0.01). The majority of antibiotic indications were treatment-related and the most common dental diagnosis was caries. The most common antibiotic prescribed in the study was amoxicillin. Compared to pre-guideline, there was significant decreased utilization of penicillin VK (pre 3.4% vs post 0%, p=0.05) and amoxicillin-clavulanate post-guideline (pre 16% vs post 8%, p=0.02). A wide variety of dosing regimens were utilized with more guideline-concordant regimens utilized post-guideline (pre 59% vs post 72%, p=0.04). On average, shorter durations of therapy were prescribed post-guideline (pre 6.8 days vs post 5.7 days, p< 0.02). Penicillin-allergic patients were prescribed less clindamycin after guideline implementation.

Conclusion

ASP initiatives and collaboration with outpatient dental clinics can improve appropriate antibiotic prescribing. As ASPs look to expand into ambulatory care settings, dental clinics should be prioritized.

Disclosures

All Authors: No reported disclosures
2272. Leftover antibiotics are a major barrier to antibiotic stewardship: results from a survey in over 500 patients in ambulatory care settings
Authors: Shah Jesal R , Trautner Barbara , Olmeda Kiara , Salinas Juanita , Laytner Lindsey , Faustinella Fabrizia , Raphael Jean , Paasche-Orlow Michael , Grigoryan Larissa
Published: November 2023

Background

Taking leftover previously prescribed antibiotics without consulting a healthcare professional is problematic in terms of efficacy, safety, and antibiotic stewardship. We sought to quantify and describe this practice in outpatient populations in a major urban area.

Methods

The cross-sectional survey was conducted in English or Spanish between January 2020 and June 2021 in six publicly funded primary care clinics and two private emergency departments around Houston. We assessed the rates and reasons for stopping prescribed antibiotics early and what was done with these leftover antibiotics. We compared the reasons for stopping antibiotics early between private and public clinic patients. Additionally, we determined the prevalence of prior leftover antibiotic use and the intention to use leftover antibiotics in the future.

Results

A total of 564 respondents (median age of 51 years) completed the survey, of whom 72% were female, 47% were Hispanic, 33% non-Hispanic black, and 16% non-Hispanic white (Table 1). 251 (45%) respondents reported stopping prescribed antibiotics early (Figure 1), including 171 (42%) who received care in the public and 80 (52%) in the private healthcare system. The most common rationale for stopping early was “because they felt better” (77%), followed by “forgot to finish all of the antibiotics” (18%). Respondents from the private system were more likely to stop early due to healthcare provider recommendations or side effects (Figure 2). Of all the respondents who stopped early, 74% kept the leftover antibiotics and 24% threw them away. Notably, 51% reported they intended to take leftover antibiotics without contacting a healthcare provider in the future. Over 26% (149) said they had previously taken leftover prescription antibiotics.

Conclusion

Stopping prescribed antibiotics early and saving residual supplies for future use are common. As patients mostly ascribed early discontinuation to feeling better, providers may have dispensed scripts for overly long durations or inappropriate indications. To curb nonprescription antibiotic use and antimicrobial resistance, we must tackle all facets of the leftover antibiotic use continuum, from over prescribing to hoarding.

Disclosures

Barbara Trautner, MD, PhD, Genentech: Grant/Research Support|Peptilogics: Grant/Research Support
2307. Respiratory Virus Testing Strategy on Admission to Hospital in a Season where SARS-CoV-2 is Co-circulating with Seasonal Respiratory Viruses
Authors: Reason Paige , Williams Victoria R , Mieusement Lorraine Maze Dit , Candon Heather , Li Xena , Kozak Robert , Leis Jerome A
Published: November 2023

Background

Syndromic multiplex testing is the mainstay of viral respiratory surveillance, yet some evidence supports the use of asymptomatic testing for SARS-CoV-2 on patient admission. We conducted a prospective quality improvement study to determine the adherence and outcomes associated with a hybrid surveillance strategy for patients being admitted to an acute care hospital who underwent testing on admission.

Methods

In November, 2022, corporate education recommended that patients with compatible viral respiratory symptoms undergo respiratory multiplex testing for 15 viral pathogens, while those without viral respiratory symptoms (considered asymptomatic) undergo SARS-CoV-2 PCR testing alone. Between December 1, 2022 to March 30, 2023, we measured the testing strategy using positivity rate, rate of omission (i.e., SARS-CoV-2 testing for symptomatic patients, defined as needing a repeat swab for multiplex within 24-hours of admission), and rate of commission (i.e., multiplex testing for asymptomatic patients). Those with detection of non-SARS-CoV-2 respiratory viruses in absence of symptoms were prospectively assessed for 24 hours for development of symptoms and roommate contacts underwent syndromic surveillance for 72-hours.

Results

Among 5659 patients tested on admission, 2868(50.6%) underwent multiplex testing while 2791(49.3%) were tested only for SARS-CoV-2. The positivity rate for multiplex testing, positivity rate for COVID SARS-CoV-2 testing, omission rate and commission rate were 249/2868(8.7%), 81/2791 (2.9%), 259/1403(17.8%), 1618/4091(39.6%), respectively. Symptom status for 165 patients was not available. Asymptomatic non-SARS-CoV-2 positive patients made up 0.6% of all admissions, of whom none developed symptoms within 24 hours, and the attack rate among roommate contacts was zero (0/20). There were only 31 additional days of precautions for asymptomatic non-SARS-CoV-2 respiratory virus detection that made up 4.4% of overall precaution-days for respiratory virus infection.

Conclusion

A hybrid surveillance strategy for patients admitted to hospital based on presence of symptoms was implemented with relatively low rates of repeat testing and asymptomatic non-SARS-CoV-2 virus detection.

Disclosures

Jerome A. Leis, MD MSc FRCPC, Ontario Hospital Association, Ministry of Attorney General of Ontario, Seneca College: Expert Testimony
2338. Robust and Persistent B Cell Responses Following Third Dose SARS-CoV-2 Vaccine Determine Protection from COVID-19
Authors: Byrne Joanne , Gu Lili , García-León Alejandro , Gaillard Colette Marie , Tomás-Cortázar Julen , Negi Riya , Alalwan Dana , Saini Gurvin , Donohue Sean , Reynolds Bearach , Kenny Grace , Leamy Kelly , O’Gorman Tessa , O’Broin Cathal , Savinelli Stefano , Feeney Eoin R , Yousif Obada , Cotter Aoife , de Barra Eoghan , Sadlier Corinna , Landay Alan , Doran Peter , Cox Rebecca J , Olesen Ole , Lelièvre Jean-Daniel , Cornely Oliver A , Gautier Virginie , Mallon Patrick
Published: November 2023

Background

The immunological memory to SARS-CoV-2 (SCV-2) vaccination has multiple components, with robust antibody (Ab) and B cell responses demonstrated post vaccination. The extent and persistence of T cell responses to vaccination remains unclear. We explored SCV-2 specific Ab, B cell and T cell responses to 3rd dose vaccine and their relationship to incident COVID-19.

Methods

In plasma from adults enrolled in a multicentre prospective cohort, sampled before, 14 days and 10 months post 3rd dose vaccine (BNT162b2) we measured anti-SCV-2 receptor binding domain (RBD) Ab by electrochemiluminescence assays. Subjects reported incident COVID-19 that occurred post vaccination. In a subanalysis, we assessed SCV-2-specific plasma cell, memory B cell and T cell responses in peripheral blood mononuclear cells after stimulation with wild type (WT) RBD, WT full Spike antigen, Omicron RBD and Omicron S1 antigens by ELISpot (Mabtech ELISpot, Sweden, Fig 1). We compared between-group differences in immunological outcomes by incident infection by Wilcoxon signed rank or Mann–Whitney U tests. Data are median (IQR) unless specified.

Results

Of 132 subjects (age 43 [32-50], 81% female (Table 1), 47 (36%) reported incident SCV-2 infection at 18 (16-21) weeks post 3rd vaccine. 76 subjects contributed to the cellular immunity subanalysis [23 of whom provided additional samples 10 months post vaccine (Table 1)]. RBD titres and B cell responses increased significantly 2 weeks post 3rd vaccine (Fig 2, p< 0.001), with RBD titres and WT-specific memory B cell responses remaining significantly higher than pre-booster vaccine levels at 10 months (Fig 2, p< 0.001). In contrast, there was no significant difference in T cell responses at two weeks or 10 months post 3rd dose vaccine (Fig 2). There was no difference in 2-week post vaccine RBD or T cell responses in those with and without incident SCV-2 infection. However, those with incident infection had significantly lower WT RBD-specific plasma and memory B cell levels (Table 2, all p< 0.05).

Conclusion

3rd dose vaccination induced robust antibody and B cell responses which persist at 10 months, but not T cell responses. Higher memory B cell responses post vaccination, rather than circulating antibody titres or T cells, are associated with protection from subsequent infection.

Disclosures

Oliver A. Cornely, MD PhD, DZIF: Advisor/Consultant|DZIF: Board Member|DZIF: Grant/Research Support|DZIF: Honoraria|DZIF: Stocks/Bonds
2340. COVID-19 Vaccine Hesitancy among Faculty Members, College Students and Health Care Workers in Lebanon
Authors: Doumat George , Tfaily Mohamad Ali , Wazzi-Mkahal Rayyan , Kanafani Zeina
Published: November 2023

Background

The COVID-19 pandemic has caused significant morbidity, mortality, and economic losses worldwide. Despite the efficacy of several vaccines in reducing SARS-CoV-2 infections, vaccination hesitancy remains a challenge. This study aimed to examine COVID-19 vaccination perceptions, beliefs, attitudes, and knowledge in Lebanon and identify unique predictors of vaccine hesitancy.

Methods

We conducted a cross-sectional online survey between March and June 2021 at the American University of Beirut and its Medical Center targeting faculty members, students, and healthcare workers. The survey included four sections, covering socio-demographics, COVID-19 perceptions, attitudes, and knowledge, with a primary focus on vaccination intent. We used a multivariate logistic regression model to investigate potential determinants of vaccine hesitancy.

Results

We had 422 respondents with an overall response rate of 94%. A large proportion of the study population were females (69%) and individuals with at least undergraduate college education (93%). Healthcare workers comprised 29.4% of all survey respondents. Of the respondents, 368 (87%) were definitely willing to take the COVID-19 vaccine, and 13% expressed various forms of vaccine hesitancy (1% definitely not willing; 8% undecided likely; 4% undecided unlikely). The most important independent predictors of vaccine hesitancy were the perception that the COVID-19 vaccine is more dangerous that the COVID-19 infection, that the vaccine development was rushed, and being a healthcare worker. Knowledge about COVID-19 infection, level of education, age, and recommendation from the respondent’s healthcare provider were negatively correlated with vaccine hesitancy. The multivariable analysis is shown in the Table.

Conclusion

We found a high COVID-19 vaccine acceptance rate and some of the factors associated with hesitancy were modifiable, including knowledge and perceptions about the disease and the vaccine, and healthcare provider recommendation. Addressing these factors is crucial for successful vaccination programs, as combatting vaccine hesitancy may be as crucial as developing a safe and effective vaccine.

Disclosures

All Authors: No reported disclosures
2362. SARS-CoV-2 Omicron Variants Associated with Less Severe Disease in Hospitalized Patients Irrespective of Baseline Risk Factors and Immunity
Authors: Lee Austin , Kawaguchi Eric , Vu Christina , Ray Brianna , Suh Joy , Vojvodic Vanya , Smith Scotti , Torres Cesar , Stafylis Chrysovalantis , Wald-Dickler Noah , Holtom Paul , Klausner Jeffrey , Khan Saahir
Published: November 2023

Background

The Omicron variant of SARS-CoV-2 saw the highest incidence of cases during the COVID-19 pandemic, yet these cases had less severe outcomes compared to earlier variants. This could be due to increased immunity from vaccination, infection of healthier patients, increased identification of less severe cases, and decreased viral pathogenicity. We examine the relative contribution of these factors to outcomes among hospitalized COVID-19 patients by comparing a cohort from the early pandemic to a cohort from the Omicron wave, subdivided by baseline immunity.

Methods

We retrospectively reviewed electronic medical records of 456 patients hospitalized for COVID during the early pandemic (03/2020 - 05/2020) and 453 patients hospitalized for COVID during the Omicron wave (12/2021 - 01/2022) at a public safety net hospital in Los Angeles, CA. We recorded demographics, clinical data, infection and vaccination history, and hospital outcomes including severe disease, defined as need for supplemental oxygen.

Results

Patients hospitalized during the early pandemic were more likely to have severe disease than those during the Omicron wave (75.9% vs 35.1%, p < 0.001). Within the Omicron cohort, “non-immune” patients without vaccination or prior infection had more severe disease than “immune” patients with prior vaccination or infection (37.8% vs 33.3%, p < 0.001). Patients hospitalized during the early pandemic were older with more medical comorbidities than during the Omicron wave; within the Omicron cohort, immune patients were older with more medical comorbidities than non-immune patients. After controlling for age and medical comorbidities via logistic regression, non-immune Omicron patients were less likely to have severe disease than early pandemic patients (OR = 0.25 [0.17-0.38]); immune Omicron patients had even lower rates of severe disease compared to early pandemic patients (OR = 0.15 [0.10-0.23]).

Characteristics of Patient Cohorts divided by Pandemic Period and Immunity Status

Risk Factors associated with Severe Disease by Logistic Regression

Conclusion

We conclude that the Omicron variant of SARS-CoV-2 produced milder disease than earlier variants irrespective of baseline risk factors and immunity, but vaccination or prior infection further reduced disease severity in the Omicron cohort. The likely presence of undetected prior infection in the Omicron cohort would weaken the first but strengthen the second conclusion.

Disclosures

All Authors: No reported disclosures
128. Validation of a rapid diagnostics platform for detecting extended-spectrum beta-lactamase resistance in gram negative bacteremia
Authors: Andrews Sam , Timbrook Tristan , Fisher Mark , Tritle Brandon
Published: November 2023

Background

Extended-spectrum beta-lactamase-producing Enterobacterales (ESBL-E) bloodstream infections (BSI) are associated with increased cost, morbidity, and mortality compared with BSI by non-ESBL-producing bacteria. Phenotypic susceptibility data from blood cultures can take up to 72 hours to result, leading to delays in appropriate antimicrobial administration and unnecessary carbapenem usage. In April 2021, University of Utah (U of U) Health began utilizing the BIOFIRE® Blood Culture Identification (BCID2) Panel platform for rapid identification of organisms and resistance genes in blood cultures, including CTX-M, the most common ESBL gene in the United States. However, other genetic determinants can lead to third-generation cephalosporin resistance. Therefore, we sought to determine the positive predictive value (PPV), negative predictive value (NPV), sensitivity, and specificity of the BCID2 platform for predicting phenotypic ceftriaxone susceptibility at our institution. Additionally, we sought to determine susceptibility of ertapenem among our isolates as co-resistance has been reported amongst CTX-M containing isolates.

Methods

This was a retrospective observational cohort study evaluating adult patients with bacteremia by select Enterobacterales species (Escherichia coli, Klebsiella oxytoca, Klebsiella pneumoniae group, Proteus, Salmonella). Data collection was performed utilizing the Enterprise Data Warehouse, clinical lab data, and medical chart review.

Results

Between 4/1/2021 and 1/31/2023, 386 isolates (in 386 patients) of Enterobacterales were identified; the majority of isolates were E. coli (280, 72.5%). Ceftriaxone resistance was observed in 45 isolates (11.6%). We found that BCID2 is highly specific (100%) and sensitive (91.1%) for predicting ceftriaxone susceptibility with high NPV (98.8%) and PPV (100%) at the U of U Health. All ceftriaxone-resistant isolates were susceptible to ertapenem.

Conclusion

The BCID2 platform is a highly sensitive and specific rapid diagnostic for determining ceftriaxone resistance at our institution. These findings should be confirmed at individual institutions to account for local resistance epidemiology.

Disclosures

Tristan Timbrook, PharmD, bioMerieux: Employee|bioMerieux: Stocks/Bonds Mark Fisher, PhD, Copan Diagnostics: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support
2428. Association of body mass index and bloodstream infections in patients on extracorporeal membrane oxygenation: A single-center retrospective cohort study
Authors: Lee Eun Hwa , Lee Jung Ah , Ahn Jin Young , Jeong Su Jin , Ku Nam Su , Choi Jun Yong , Yeom Joon-sup , Song Young Goo , Park Se Hee , Kim Jung Ho
Published: November 2023

Background

Obesity is associated with poor clinical outcomes in critically ill patients. However, under some clinical conditions, obesity has protective effects. Bloodstream infections (BSI) are one of the most common nosocomial infections associated with extracorporeal membrane oxygenation (ECMO) support. BSI during ECMO is associated with higher mortality rates and poorer clinical outcomes. This study analyzed whether body mass index (BMI) was associated with BSI during ECMO and in-hospital mortality.

Methods

All adult patients who had received ECMO support for >48 h were included in the analysis. The total duration of ECMO support, in-hospital mortality, and BSI were analyzed according to BMI categories. The Cox proportional hazards model was used to compare the risk of BSI according to different BMI categories.Figure 1.Study flow chart

Results

A total of 473 patients were enrolled in the study. The average age was 56.5 years old and 65.3% were men. The total ECMO duration was approximately 11.8 days with a mortality rate of 47.1 %. The incidence of bacteremia and candidemia were 20.5% and 5.5%, respectively. There was no significant difference in bloodstream infection rates (p=0.784) or mortality rate (p=0.253) among the five groups. The underweight group required ECMO for respiratory support, whereas the overweight and obese groups required cardiogenic support (p< 0.0001). However, there was no significant difference in the development of BSI during ECMO support or in-hospital mortality among any of the five groups.

Conclusion

Patients with higher or lower BMI did not show an increased risk of BSI or in-hospital mortality associated with ECMO support.Figure 2.Forest-plot for risk of bloodstream infection occurrence in different body-mass index categories.Figure 3.Kaplan-Meier analysis comparing the survival rate in different BMI groups.

Disclosures

All Authors: No reported disclosures
2452. Prevalence of Antimicrobial ReSistanCE iN BloodStream Infections in HOspitalized (BSI) PatieNts in BRazil (ASCENSION-BR): Preliminary Results of a Multicenter Study
Authors: Antochevis Laura C , Barth Afonso , Wilhelm Camila , Carrilho Cláudia , Arns Beatriz , Guimarães Luiz Felipe , Starling Carlos E , Coelho Andre , Mendes Elisa , Rocha Verônica , Martins Amanda , Girão Evelyne , Telles João , Sudbrack Letícia , Leão Robson , Zavascki Alexandre
Published: November 2023

Background

Carbapenem-resistant Enterobacterales (CRE), P. aeruginosa (CRPA), A. baumannii (CRAB), methicillin-resistant S. aureus (MRSA) and vancomycin-resistant E. faecium (VRE) are major multidrug-resistant (MDR) bacteria causing healthcare-associated infections. There is no multicenter study addressing the prevalence of these MDR bacteria in Brazil. We report the preliminary results of the ongoing ASCENSION-BR study evaluating the prevalence of these microorganisms in BSI in hospitalized patients in this country.

Methods

This prospective multicenter study has been conducted in 13 hospitals distributed in 4 of 5 Brazilian regions. From 15th August to 31st April (to be finished on 14th August 2023), each hospital recruited patients for a period of up to 6 months. Adult patients hospitalized for at least 48h, with positive blood cultures with Enterobacterales, P. aeruginosa, A. baumannii, S. aureus and Enterococcus spp. were eligible. More than one BSI of the same patients were included if caused by a distinct bacteria. MDR isolates were sent to a central laboratory where isolates were re-identified by MALDI-TOF-MS.

Results

A total of 10 hospitals recruited patients for 6 months(m), 1 for 5m, and 2 for 1m. 1231 bacterias were isolated from 1091 BSI episodes (118 were polymicrobial), and 442 (35.9%) were MDR. Enterobacterales were the most common isolates in BSIs (659, 75.3%), followed by S. aureus (221, 18.0%), A. baumannii (113, 12.9%), Enterococcus spp. (135, 11.0%: 48 [35.6%] E. faecium and 84 [62.2%] E. faecalis) and P. aeruginosa (103, 8.4%). Among Enterobacterales, the most frequent species were K. pneumoniae (275, 41.7%), E. coli (126, 19.1) and Enterobacter spp. (69, 10.5%). A total of 224 (34.0% of Enterobacterales) BSIs were caused by CRE (155 [69.2%] K. pneumoniae, 27 [12.1%] Serratia marcescens, 15 [6,7%] Enterobacter spp., and 27 [12.1%] other 11 species. A total of 100 (88.5% of A. baumannii) isolates recovered in BSIs were CRAB and 38 (36.9% of P. aeruginosa) were CRPA. Among Gram positives, 50 (22.6% of SA) were MRSA, and VRE represented 93.3% of E. faecium and 3.3% of E. faecalis isolates.

Conclusion

High prevalence of MDR in BSI, notably in A. baumannii, were found among hospitalized patients in Brazil.

Disclosures

João Telles, MD, PhD, MSD: Advisor/Consultant|MSD: Speaker|Pfizer: Advisor/Consultant|Pfizer: Speaker|União Química: Advisor/Consultant|União Química: Speaker Alexandre Zavascki, MD, PhD, Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support
2468. The Genomic Epidemiology of Carbapenemase-Producing Enterobacterales (CPE) in Ontario, Canada, 2016
Authors: Jamal Alainna J , Tijet Nathalie , McGeer Allison , Baqi Mahin , Borgia Sergio , Ciccotelli William , Farshait Nataly , Katz Kevin , Mehta Mamta , Goneau Lee , Mertz Dominik , Small Lorne N , Melano Roberto
Published: November 2023

Background

Carbapenemase-producing Enterobacterales (CPE) are among the most urgent of antimicrobial resistance threats. In south-central Ontario, Canada, over one-third of CPE cases are associated with local healthcare and the incidence of such CPE cases is rising steadily. We integrated whole-genome sequencing (WGS) and CPE population-based surveillance data to gain insights into CPE transmission dynamics in Ontario, Canada.

Methods

We included all incident CPE isolates received at the Public Health Ontario Laboratory as part of a voluntary surveillance program from Jan. 1 to Dec. 31, 2016 in Ontario, Canada (population ∼13.5 million). All isolates underwent Illumina WGS. MLST was determined for all isolates, and single nucleotide variant (SNV) analysis was performed by species. SNV analyses were combined with epidemiological data from the Toronto Invasive Bacterial Diseases Network to identify transmission clusters.

Results

There were 206 incident CPE isolates from 176 patients. Most common species were Escherichia coli (95, 46%) and Klebsiella pneumoniae (76, 37%), and most common carbapenemases produced were NDM (77, 37%), OXA-48-like (68, 33%), and KPC (45, 22%). There was variability in MLST, with ST167 being most common among E. coli (10, 11%), and ST147 being most common among K. pneumoniae (13, 17%). There were 14 clusters with 34 (17%) CPE isolates belonging to 33 (20%) unique patients total (Table). Cluster size range was 2-5 patients. Time from first to last identified case in clusters ranged from 0 to 258 days. In 8 clusters, the index case likely acquired CPE during prior hospitalization abroad, with subsequent direct or indirect transmission to other patients in the cluster. In 5 clusters, all patients likely acquired CPE at the Ontario hospital where their CPE was detected.

Conclusion

There was variability in CPE species and MLST as well as carbapenemase produced. Almost one fifth of patients belonged to a transmission cluster, with transmission lasting many months in some clusters. These data highlight challenges with CPE local transmission and a need to intensify control measures.

Disclosures

All Authors: No reported disclosures
2498. An evaluation of a mandatory Hepatitis C Virus screening bill in perinatally exposed infants in Kentucky
Authors: Guy Laura , Yarber-Cambron Lisa , Herring Nicholas , Jennings Hunter , O’Connell Katherine , Scott Traci
Published: November 2023

Background

In the last decade, Hepatitis C virus (HCV) rates have dramatically increased in women of child-bearing age nationally and in Kentucky. Correspondingly, there has been a documented increase in the percentage of infants born with HCV. In response to this alarming increase in HCV cases, Kentucky became the first state nationwide to implement a mandatory universal HCV screening of pregnant women in July of 2018. This study evaluates the efficacy of the mandatory universal HCV screening bill KRS 214.160 SB 250.

Methods

Using laboratory data, a retrospective cohort of HCV-positive women who sought obstetric care at Norton Healthcare between January 1, 2017, and December 31, 2019, and subsequently delivered live infants were identified. Mother-infant dyads were grouped into pre- (before July 1st, 2018) or post-implementation (after July 1st, 2018) groups based on the infant’s date of birth. Manual chart reviews were utilized to identify screenings for HCV in both mothers and infants. Adequate testing was defined by the current CDC recommendations.

Results

1.8% of infants in the study were diagnosed with congenital HCV infection. A modest increase of testing per CDC guidelines occurred during the post-implementation study period. Only 190 infants had at least one HCV laboratory result during the study period (68.1%). Only 55 children in the cohort were adequately tested for HCV during the study period. Fifteen infants (14.71%) born during the pre-implementation period were adequately tested per the guidelines. Only 55 (24.4%) of the infants born during the post-implementation period were tested per CDC guidelines (Fig. 1).

Conclusion

Overall, HCV screening is still inadequate in Kentucky. However, there was a modest increase in the number of adequate HCV infant screenings. 11% of the infants in the cohort had no observable follow-up for HCV although almost all children had documented perinatal exposure to HCV. The documented vertical transmission rate in this cohort is lower than the frequently cited 5.8%. More research is required to evaluate the efficacy of the mandatory HCV screening bill in Kentucky.

Disclosures

Laura Guy, BS, CRCC, Gilead Sciences, Inc: Grant/Research Support Lisa Yarber-Cambron, MSN, RN, AMB-BC, Gilead Sciences, Inc: Grant/Research Support Nicholas Herring, BS, MPH, Gilead Sciences, Inc: Grant/Research Support Hunter Jennings, BS, Gilead Sciences, Inc: Grant/Research Support Katherine O'Connell, BS, MPH, Gilead Sciences, Inc: Grant/Research Support Traci Scott, MD, Gilead Sciences, Inc: Grant/Research Support
2556. A Phase 1, Open-Label, Single Dose Study to Evaluate the Pharmacokinetics (PK), Safety, and Tolerability of Epetraborole Tablets and the Impact of Alcohol Dehydrogenase (ADH) Genotype on the PK of Epetraborole and Metabolite M3 in Healthy Japanese Adult Subjects
Authors: Patel Gina , Castañeda-Ruiz Bibiana , Yoshihara Tatsuya , Krause Kevin M , O’Shea Kevin , Kammerer Linda , Maier Gary , Long Jennifer , Smith Alex , Chanda Sanjay , Moore Stephanie , Eckburg Paul B
Published: November 2023

Background

Epetraborole (EBO), an orally available bacterial leucyl transfer RNA synthetase inhibitor with potent activity against nontuberculous mycobacteria, is under clinical development for treatment-refractory MAC lung disease. Nonclinical studies suggest that metabolism of EBO to metabolite M3 may involve oxidation by ADH. The goal of this study was to evaluate the impact of ADH genotype on the PK of EBO and M3 in healthy Japanese subjects.

Methods

In this open-label trial, a single 500 mg EBO dose was administered to subjects in 3 cohorts defined by ADH1B genotype (*1/*1, *1/*2, or *2/*2). EBO and M3 plasma concentrations were measured by a validated LC-MS/MS method, and plasma EBO and M3 PK were determined using non-compartmental methods. Standard clinical and laboratory evaluations and treatment-emergent adverse events (TEAEs) were assessed.

Results

18 subjects were enrolled (6/cohort). EBO was rapidly absorbed, with M3 subsequently appearing in plasma. After reaching Cmax, EBO and M3 concentrations declined with a geometric mean t1/2 of 10.7 to 11.4 h and 26.7 to 33.1 h, respectively. EBO exposures (Cmax and AUC) were similar between Cohort 1 and Cohort 2, while exposures were 1.2- to 1.4-fold higher in Cohort 3 (Table); however, exposure of M3 was similar across all cohorts. Compared to Cohort 1, M3:EBO ratios for Cohort 3 were generally similar for Cmax and were approximately 26% lower for AUC. No apparent differences in t1/2 were observed across cohorts for either EBO or M3. No TEAEs or clinically significant changes in clinical laboratory parameters, vital signs, physical examinations, or ECGs were reported in this study.

Conclusion

Administration of EBO in Japanese subjects with varying ADH1B genotypes had no meaningful effect on EBO or M3 plasma exposure. The slightly increased EBO exposures associated with the 500 mg dosage in subjects with ADH1B *2/*2 genotype were within the range of tolerable exposures. Oral EBO was well tolerated in this study; no TEAEs were reported. This Phase 1 study did not identify any risk that would preclude evaluation of oral EBO administered 500 mg daily in patients with different ADH1B genotypes, including Japanese patients.

Disclosures

All Authors: No reported disclosures
2565. In vitro synergistic bacterial killing of imipenem and ceftaroline against Mycobacterium abscessus; a static concentration time-kill analysis
Authors: Shin Eunjeong , Nantongo Mary , Holland Steven M , Kreiswirth Barry N , Dousa Khalid M , bonomo Robert A
Published: November 2023

Background

Mycobacterium abscessus (Mab) represents a significant clinical challenge, with a rising incidence in recent times. The current therapeutic approach, which involves prolonged IV administration of amikacin, is associated with notable toxicities. Consequently, there is a pressing need to explore safe alternatives in antibiotic therapy. This study aimed to evaluate the in-vitro synergistic effect of a double β-lactam (DBL) combination which is safe for all ages.

Methods

We conducted static concentration time-kill (SCTK) studies utilizing Mab strain ATCC19977 over 10 days in duplicate. SCTK evaluated the impact of imipenem (IPM) and ceftaroline (CFT) in both monotherapy and combination therapy on bacterial killing (inoculum: 6 log10 CFU/mL). To counteract the recognized extent of thermal degradation of β-lactams, predetermined quantities of IPM and CFT were added every 24 hours. Synergistic killing was estimated in the S-ADAPT software. In addition, the post-antibiotic effect (PAE) was measured following a 2-hour exposure to β-lactams. The β-lactams were removed by exchange with drug-free broth after centrifugation.

Results

DBL of IPM+CFT exhibited synergistic bactericidal activity, surpassing that of monotherapy with rapid regrowth observed in 1-3 days. Monotherapy demonstrated up to ∼1.5 log10 killing followed by near-complete regrowth over a period of 10 days. DBL demonstrated significant synergistic killing, resulting in rapid and the most extensive reduction (∼3.5 Log10 CFU/mL) and suppression of regrowth over 10 days. The addition of a β-lactamase inhibitor reduced the CFT concentration required for bacterial killing, resulting in synergistic bacterial killing at an achievable concentrations in-vivo mouse studies and clinical trials in the future. Furthermore, PAE were 4 minutes for IPM and 2 hours for CFT. Strikingly, the DBL at a concentration of 1xMIC demonstrated noteworthy bacteriostatic activity, with the suppression of bacterial growth lasting up to 14 h.

Conclusion

DBL therapy yielded the most rapid and extensive killing of Mab with limited regrowth. The β-lactamase inhibitor was efficacious in inhibiting a broad-spectrum β-lactamase (blaMab). The prolonged PAE observed in the DBL of IPM plus CFT may prove beneficial for intermittent dosing regimen.

Disclosures

Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support
2574. Serotype Distribution of Streptococcus pneumoniae and Pneumococcal Vaccine Coverage in Adults in Turkey between 2019 and 2022
Authors: Hasçelik Gülşen , Hasdemir Gökboğa Münevver U , Hazırolan Gülşen , Ay Altıntop Yasemin , Öksüz Lütfiye , Telli Murat , Özakın Cüneyt , Aydemir Sabire Ş , Baysan Betil Özhak , Birinci Asuman , Yaman Akgün , DURMAZ Gül , Gövde Özkaya Esra , Çizmeci Zeynep , Mete Mahmut , Özbek Özgen A , Uslu Hakan , Öztürk Candan , Güdücüoğlu Hüseyin , Duman Yücel , Zer Yasemin , Karadağ Öncel Eda , Karbuz Adem , Ceyhan Mehmet
Published: November 2023

Background

Streptococcus pneumoniae infections are challenging due to pneumococci having more than 100 serotypes. This ongoing study is aimed to evaluate serotype distribution of S. pneumoniae causing pneumococcal infections in adults ( >18 years) and to provide a perspective regarding serotype coverage of both current and future pneumococcal vaccines.

Methods

Pneumococcal strains were collected from 22 centers between January 2019 and December 2022. Serogrouping was performed using latex particle agglutination, and serotyping was performed by the conventional Quellung reaction using commercial type-specific antisera (Statens Serum Institut, Copenhagen, Denmark).

Results

During the study period, 212 pneumococcal strains (156 males [73.6%] and 56 females [26.4%]) were collected from adults over 18 years of age. Of the isolates, 114 (53.8%) were from patients < 65 years old and 98 (46.2%) were from patients ≥65 years old. The majority of isolates were obtained from blood (n=123, 58%) followed by bronchoalveolar lavage [BAL] (n=38, 17.9%) and cerebrospinal fluid (CSF) (n=25, 11.7%). The most frequently isolated serotypes were 3, 9N and 8. The vaccine coverage for PCV13, PCV15, PCV20, and PPV23 was 36.3%, 36.7%, 50.9%, and 56. 1%, respectively, in all isolates. The vaccine serotype coverage rates in the study group are shown in Table-1.

Conclusion

It has been observed in time that while vaccine serotypes are decreasing, serotypes not covered by vaccines are increasing. Accordingly, surveillance is essential to determine vaccination policy.

Disclosures

Mehmet Ceyhan, n/a, Pfizer Pharmaceuticals, Istanbul, Turkey: Advisor/Consultant|Pfizer Pharmaceuticals, Istanbul, Turkey: Grant/Research Support
2576. Piperacillin-Tazobactam or Cefepime for Treatment of Third Generation Cephalosporin Resistant Pneumonia in Intensive Care Unit Patients
Authors: DeLaurentis Clare , Hokunson Todd W , Nelson Brian , Annavajhala Medini K , Uhlemann Anne-Catrin , Gomez-Simmonds Angela
Published: November 2023

Background

Infections caused by Enterobacterales resistant to third generation cephalosporins (Ceph-RE) are rising in incidence. Carbapenems are frequently used to treat Ceph-RE infections based largely on studies of patients with bacteremia. Data evaluating alternative antibiotic options in pneumonia are limited. We assessed outcomes in intensive care unit (ICU) patients with Ceph-RE pneumonia treated with piperacillin-tazobactam (TZP) and cefepime (FEP) versus carbapenems.

Methods

Adult ICU patients with pneumonia and positive respiratory culture for Ceph-RE between 1/2015-7/2022 were identified from electronic records. The antibiotic given after sensitivity test results and for > 72 hours (h) was termed the definitive agent. Patients who had polymicrobial pneumonia, severe infection at another body site, or were treated for < 72h or with an agent other than a carbapenem, TZP, or FEP were excluded. Nanopore sequencing was used to identify β-lactamase genes (n=68), and TZP and FEP minimum inhibitory concentrations (MIC) were determined by broth microdilution (n=64). The primary outcome was survival to 30 days or hospital discharge. Outcomes were compared in univariable and multivariable analyses.

Results

Of 81 included patients, 56% were treated with a carbapenem and 44% received TZP or FEP. Patients receiving carbapenems had numerically higher Pitt Bacteremia Scores (PBS) and rates of severe sepsis (Figure 1). 52/68 isolates harbored an extended-spectrum β-lactamase gene; AmpCs were identified in 13 isolates and OXA-1 in 12. The majority of isolates were susceptible to TZP (91%) and FEP (64%). 73% and 92% of patients treated with TZP and FEP, respectively, met the primary outcome versus 67% of carbapenem recipients. In a multivariable model, only severe sepsis/septic shock was an independent predictor of poor outcome (OR 3.1, 95% CI 1.1-9.7, p=0.04); TZP or FEP use trended toward improved survival (OR 0.3, 95% CI 0.1-1.05, p=0.07). Survival did not differ based on the underlying resistance mechanism.

Conclusion

While ICU patients receiving carbapenems had more severe illness and worse outcomes, TZP and FEP appeared to be effective agents for patients with less severe pneumonia. Alternative therapies are essential to curb ongoing increases in carbapenem resistance.

Disclosures

Anne-Catrin Uhlemann, MD, PhD, Merck: Grant/Research Support
2591. Anxiety and depression among patients with non-tuberculous mycobacterial disease in Shanghai: A cross-sectional study
Authors: yuan zheng , Hu Bijie , ni sikang
Published: November 2023

Background

To understand the mental health status and its influencing factors among patients with non-tuberculous mycobacterial disease and to provide a reference for medical staff to formulate scientific and feasible intervention strategies.

Methods

A total of 114 patients diagnosed with non-tuberculous mycobacillosis during hospitalization in the Department of Infection from September 2020 to April 2021 were selected as the research participants. Participants’ mental health status and related factors were evaluated using a self-made general patient information questionnaire, self-rating Anxiety Scale (SAS), and self-rating Depression Scale (SDS).

Results

Among 114 patients with non-tuberculous mycosis, 61 (53.51%) exhibited depressive symptoms, and the SDS score was 51.15 ± 13.04, which was higher than the national norm of 41.88 ± 10.57 (P < 0.05); further, 39 patients (34.21%) showed anxiety symptoms, and the SAS score was 45.75 ± 10.81, which was significantly higher than the national norm of 29.78 ± 10.07 (P < 0.05). Body mass index and monthly household income had significant effects on depression in patients with non-tuberculous mycobacterial disease (P < 0.05). Educational level had a significant effect on the anxiety state of patients with non-tuberculous mycobacterial disease (P < 0.05).

Conclusion

Patients with non-tuberculous mycobacterial disease are prone to depression and anxiety. Nurses should pay attention to it in clinical work for the timely identification of and intervention for anxiety and depression and intervene.

Disclosures

All Authors: No reported disclosures
2596. Title: The Dynamics Of Invasive Pneumococcal Disease (IPD) due to Streptococcus pneumoniae and Impact Of Pneumococcal Conjugate Vaccines (PCVs) In Canada From 2000-2019
Authors: Ramos Bernice N , Khatri Vadlamudi Nirma , Martin Irene , Tyrrell Greg , Brousseau Nicholas , Griffith Averil M , Sadarangani Manish
Published: November 2023

Background

IPD remains a major cause of morbidity and mortality globally despite the implementation of PCVs in childhood immunization programs, due to the emergence of non-vaccine serotypes (NVTs) and persisting vaccine types. Newly approved vaccines such as PCV15 and PCV20 may address some of these issues. This study aimed to describe the epidemiology of IPD in Canada from 2000-2019 after PCV7 and PCV13 approval in 2001 and 2010, respectively, and evaluate the potential future impact of PCV15 and PCV20.

Methods

Data were collected from IPD cases in children and adults captured by the Pneumococcal Reference Laboratory in Alberta and the National Microbiology Lab during 2000-2019; this includes the majority of isolates from IPD across Canada, excluding Quebec. We calculated annual age-, and serotype-specific incidence rates and serotype distribution using population estimates from Statistics Canada.

Results

A total of 37,921 isolates from IPD cases were included in the analyses. After PCV7 introduction, IPD due to PCV7 serotypes decreased by 64% (2.2 to 0.8 cases per 100,000 population per year) from 2001 to 2010, while PCV13/non-PCV7 serotypes increased between 2004 and 2010 from 1.0 to 3.8 per 100,000 per year. After PCV13 introduction, IPD due to PCV13/non-PCV7 serotypes decreased by 53% (3.8 to 1.8 per 100,000 per year) between 2010 and 2019. The overall rate initially decreased from 8.7 to 7.6 per 100,000 between 2010-2014 but increased to 9.6 per 100,000 in 2019. From 2010 to 2019, IPD incidence increased by 63% (0.8 to 1.3 per 100,000 per year) for PCV15/non-PCV13 serotypes and by 33% (1.2 to 1.6 per 100,000) for PCV20/non-PCV15 serotypes. The proportion of serotypes in 2019 covered by PCV15 and PCV20 was 32% and 45% in infants aged < 2 years and 43% and 56% in adults aged ≥65 years, respectively. There was an increased IPD burden observed for some PCV13 serotypes: serotype 3 increased from 0.7 to 1.1 per 100,000 per year between 2010 and 2019 and serotype 4 increased from 0.2 to 0.8 per 100,000 per year between 2014 and 2019.

Conclusion

IPD rates in Canada continue to increase despite the widespread use of PCV13. While PCV15 and PCV20 hold promise in addressing prevalent recently circulating serotypes, there remains a need to develop vaccines with broader coverage considering the constant emergence of NVTs.

Disclosures

Nirma Khatri Vadlamudi, PhD, MPH, Pfizer Canada: Grant/Research Support Greg Tyrrell, PhD, Merck Canada: Advisor/Consultant|Merck Canada: Grant/Research Support Manish Sadarangani, BM BCh, FRCPC, DPhil, GlaxoSmithKline: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support|Symvivo: Grant/Research Support|VBI Vaccines: Grant/Research Support
2605. Etiology of Community Acquired Lower Respiratory Tract Infection (LRTI) in Children
Authors: Yoo Byungsun , Yune Ilha , Kim Eu Suk , Lim Sungyoon , Yoo Sooyoung , Jung Seyoung , Kim Miyoung , Kim Junesung , Kim Daehwan , Lee Hyunju
Published: November 2023

Background

Community acquired lower respiratory tract infection (LRTI) is a leading cause for hospitalization in children and an important cause for antibiotics. Despite the large burden of LRTI, in many cases it is difficult to determine the pathogen. In this study, we aimed to describe the etiology of LRTI in children and analyze factors associated with bacterial or viral infection.

Methods

Electronic medical records of children < 19 years of age diagnosed with LRTI (including pneumonia, bronchiolitis or bronchitis) at Seoul National University Bundang Hospital from January 2005 to June 2019 were retrospectively reviewed.

Results

A total of 5,954 cases of LRTI were identified. Among them 74.3% were pneumonia and 25.7% were bronchiolitis or bronchitis. Mean age was 22 (IQR 38) months. 52.6% were < 2 years of age and 29.7% were 2-4 years of age. Among all LRTI, 48% had a proven pathogen; 55.1% were viral, 46.3% were Mycoplasma pneumoniae and 1.3% were bacterial. Among viruses, respiratory syncytial virus (41.9%) was most common followed by influenza (7.8%), parainfluenza (7.1%) and adenovirus (4.1%). Among bacteria pneumonia, Streptococcus pneumonaie was most common which accounted for 58.1%. Among physical findings, wheezing, stridor, chest retraction and coarse breathing sounds were seen more commonly in viral infections (P< 0.05, respectively), whereas decreased breathing sound was commonly found in both M. pneumoniae and bacterial infections (P< 0.05, respectively). For treatment, 26.5% were treated with supportive care, 72.0% received antibiotics, 1.0% received antiviral agents and 5.6% were prescribed with steroids. Among patients 16.4% needed oxygen supply, 1.7% were admitted to the intensive care unit and 1.4% required respiratory support. There was one case of mortality (0.02%).

Conclusion

In children with LRTI, among cases where the pathogen was detected, more than half were due to viral infections, followed by M. pneumoniae, and a few cases of bacteria. In this study, we found a relatively large portion of children may have been treated with unnecessary antibiotics. LRTIs in children are a significant clinical burden and calls for a need for antibiotic stewardship.

Disclosures

All Authors: No reported disclosures