bluuebunny/crossref_metadata_2025 huggingface dataset:
298. A Novel Murine Model of Neonatal Staphylococcus aureus Colonization Induces Changes in the CD4 T cell Compartment and Protects from Lethal Bacteremia
Authors: Olson Patrick D , Bubeck-Wardenburg Juliane
Published: November 2023

Background

Staphylococcus aureus is a leading infectious cause of invasive bacterial infection in the United States. The pathogen’s capacity to cause disease is due, in part, to its ability to asymptomatically colonize the human host. Classically, the nose has been presumed to be the primary colonization site, but there is increasing evidence that the gastrointestinal tract may be a fundamental niche occupied during S. aureus colonization. There remain significant deficits in preclinical modeling of invasive S. aureus infection; Laboratory mice are commonly employed for modeling of S. aureus infection, but are rarely colonized by or pre-exposed to S. aureus. This contrasts with the human interaction with the pathogen, where a vast majority of humans demonstrate a specific adaptive response to S. aureus and a plurality of patients have lifelong colonization. To overcome this deficit, we designed a novel neonatal mouse model of asymptomatic intestinal S. aureus colonization.

Methods

Neonatal mice were subjected to oral gavage with S. aureus at day 10 of life; colonization was followed by fecal S. aureus titer. Infection outcomes were compared between mock- and S. aureus colonized mice.

Results

Mice from internal breeding and external vendors had no detectable S. aureus in the nasopharynx or feces at all time points tested. We found that adult mice are unable to be durably colonized by S. aureus despite multiple methods of inoculation. We identified that neonatal mice have a narrow, early window of susceptibility when they can be durably colonized, demonstrating robust fecal titers of S. aureus sustained through adulthood. Intestinal exposure to S. aureus shifted the nature of the colonic T cell compartment to encompass a greater proportion of CD4 T regulatory cells and a decreased frequency of GATA3+ CD4 cells. Finally, colonized mice demonstrated protection from severe infection, mimicking what is seen in humans.

Conclusion

Our findings support the hypothesis that gastrointestinal colonization influences the development of systemic immunity against S. aureus. This model will allow exploration into the mechanism of protective immunity against S. aureus and may inform the development of novel therapeutic and vaccination approaches to mitigate staphylococcal disease.

Disclosures

All Authors: No reported disclosures
299. Distinct TGF-β1 Patterns in Patients with Sepsis and Non-alcoholic Fatty Liver Disease
Authors: Papic Neven , Vrsaljko Nina , Radmanic Leona , Simicic Petra , Krznaric Juraj , Gjurasin Branimir , Zidovec Lepej Snjezana , Vince Adriana
Published: November 2023

Background

There is growing evidence that non-alcoholic fatty liver disease (NAFLD) might impact infection course and outcomes. However, the immune responses in patients with NAFLD and sepsis have not been described. TGF-β1 is a key biological regulator that exhibits broad immunosuppressive and healing effects in sepsis. Although TGF-β pathway dysregulation is described in patients with NAFLD, TGF-β responses in patients with sepsis and NAFLD are still unknown. The aim was to determine whether patients with NAFLD and sepsis have distinct circulating TGF-β1 patterns.

Methods

A prospective cohort study included 80 patients with community-acquired sepsis (SOFA > 2); 40 patients with NAFLD and 40 without NAFLD. TGF-β1 serum concentrations were analyzed at admission and on day 5 of hospitalization. Routine demographic, laboratory, microbiological, and clinical data were collected. Data are presented as frequencies and medians with interquartile ranges.

Results

The main sources of sepsis were respiratory (25, 31.2%), urinary (18, 22.5%), and skin and soft tissue infection (16, 20%). Groups were matched regarding age (65 [53-74] years), sex (39 males), and comorbidities, except for obesity which was more frequent in the NAFLD group (BMI of 35 [28-40] vs 26 [22-28] kg/m2). There were no differences in routine laboratory findings including CRP, procalcitonin, lactate, and WBC, except for GGT which was higher in the NAFLD group (60 [31-115] vs 33 [21-69] IU/L). Upon admission, patients with NAFLD had higher TGF-β1 concentrations than patients without NAFLD (207 [87-350] vs 65 [13-172] pg/mL). However, distinct temporal changes were observed on day 5; while TGF-β1 decreased in most patients with NAFLD (in 24, 60%, median of 140 [43-305] pg/mL), in the non-NAFLD group TGF-β1 concentrations increased in 34 (85%) patients to 151 [82-367] pg/mL), as shown in Figure 1.

Conclusion

Patients with NAFLD have higher baseline TGF-β1 serum concentrations that fail to further increase, but rather decrease in a compensatory anti-inflammatory phase of sepsis. A better understanding of these TGF-β1 changes could potentially help elucidate the complex and aberrant immune responses in NAFLD patients during sepsis.

Disclosures

All Authors: No reported disclosures
300. Disturbance of Gut Microbial Diversity in ICU Patients from Colombia is Driven by Multi-Drug Resistant Organisms (MDRO) Colonization
Authors: Parada Torres Alexandra , Castro Betsy , Malavet Thomas , Forero Nicolas , Matiz Juan , Rodriguez Yordy , Zambrano Luis , Melissa Ordoñez Karen , Santamaria Alejandra , Ospina Fidel , Beltran Jaime , Guevara Fredy , Martinez Juliana , Porras Alexandra , Sarmiento Paola , Aroca Luisa , Mora Alejandra , Arias Cesar A , Paola Carvajal Lina , Rincon Sandra , Reyes Jinnethe
Published: November 2023

Background

Gut microbiota plays a critical role in health, with essential functions in physiology, metabolism, immunity, regulation, and protection against pathogens. Critically-ill patients admitted on the ICU experience perturbation in the microbiota, with reduction in the phylogenetic diversity and composition. Here, we aimed to investigate the rectal microbiota in patients admitted on the ICU from Colombia, focused on MDRO colonization.

Methods

Microbiome analysis and microbiological screening for MDRO and WGS were performed in rectal swabs taken on admission day from 180 patients from 5 ICUs. Microbiome analysis was determined by 16S rRNA sequencing using Illumina Miseq platform. alpha-diversity metrics were calculated by Richness, Simpson, and Shannon indexes, and beta-diversity was determined using Similarity Percentages (SIMPER) analysis. Patients were grouped into 2 cohorts: MDRO-colonized and non-colonized. Clinical data was collected using REDCap.

Results

MDRO colonization was detected in 13 patients (7%), and Enterobacter cloacae complex was the most prevalent microorganism (38%), followed by K. pneumoniae (23%), and P. aeruginosa (15%). Of these MDRO, 23% and 15% harbored KPC-2 and KPC-3/OXA-9 combination, respectively. Prevotella and Bacteroides were the most abundant genus in the microbiota of all patients. Interestingly, microbiota of MDRO-colonized patients showed lower diversity (Shannon p:0.0025, Simpson p: 0.0031 and richness 0.012) and had less bacterial taxa than the observed in the non-colonized group (n=167), in which Bacteroides, Porphyromonas, Campylobacter, and Oscillospiraceae genus were exclusively detected. Moreover, Parabacteroides was a genus exclusively identified in the MDRO colonized group. Further, 14 genus including Oscillospiraceae, Lactobacillus, and Faecalibacterium related to beneficial functions were lower in abundance from MDRO-colonized patients, whereas some pathobionts were present in high abundance in this group. Most of patients were men (58%); median age was 59 y/o. Charlson comorbidity index 4 (IQR=1-6).

Conclusion

Loss in microbial diversity, with low abundance of beneficial microorganisms were associated with MDRO gut colonization in ICU patients from Colombia.

Disclosures

Karen Melissa Ordoñez, n/a, Pfizer: Advisor/Consultant|Pfizer: Honoraria
302. Investigating NAI Titer as a Neutralizing IAV Correlate of Protection
Authors: Rumfelt Kalee E , Lauring Adam S , Martin Emily T , Monto Arnold , Petrie Joshua
Published: November 2023

Background

Influenza vaccines are updated each year to maximize protection against circulating strains. This process relies on Correlates of Protection (CoPs) that compare an assay’s measure of an immune response with the level of protection. Three common CoPs for Influenza A Virus (IAV) are Hemagglutinin (HA) Inhibition (HAI), Neuraminidase (NA) Inhibition (NAI), and microneutralization (MN) titers. These capture different aspects of the immune response, and the degree to which NA antibodies provide protection is not well understood. Determining how these assays are related has implications for understanding the contribution of multiple antibody-based mechanisms of protection against infection.

Methods

Pre-/ post-season sera were collected from individuals enrolled in the HIVE study for the 2016-17 and 2017-18 seasons. HAI and NAI assays were performed on 216 samples from 139 individuals for A/Hong Kong/4801/2014 and A/Singapore/INFIM-16-0019/2016. MN assays were performed on 179 samples from 81 individuals using A/Hong Kong. Linear regression was used to assess the association between the NAI and MN titers, controlling for HAI titers. Descriptive statistics were used to determine the level of antibody cross-reactivity of the subsequently-circulating A/Singapore NA, with a 4-fold difference in titer indicating discordance.

Results

After adjusting for age, the regression model produced beta estimates of 0.16 for HAI and 0.54 for NAI titers, but neither were significant (HAI p= 0.09 NAI p= 0.08). The percentage of individuals with NAI titers that were discordant for A/Hong Kong was 14.8% in 2016-17 and 20.8% in 2017-18. No individuals had A/Singapore titers that were discordant compared to A/Hong Kong titers.

Conclusion

Although not significant, we found NAI assay titers were more strongly associated with LMN titers, suggesting that NA antibodies provide some degree of neutralizing activity. A small proportion of individuals had discordant NAI results, which indicate limited cross-reactivity across strains. This raises questions regarding differences in antibody production toward differing NAs. The findings of this study suggest that NA antibodies are capable of neutralizing IAV and this activity differs across strains and individuals.

Disclosures

Adam S. Lauring, MD, PhD, Roche: Advisor/Consultant|Sanofi: Advisor/Consultant Emily T. Martin, PhD, MPH, Merck: Grant/Research Support Arnold Monto, MD, Roche: Advisor/Consultant|Roche: Honoraria Joshua Petrie, PhD, CSL Seqirus: Grant/Research Support
303. Tissue-compartment specific differences in T-cell response found in 44 fatal COVID-19 cases
Authors: Stantliff Trevor M , Platt Andrew , Stein Syndey R , Oguz Cihan , Vannella Kevin M , Ramelli Sabrina , Hewitt Stephen , Chertow Daniel S
Published: November 2023

Background

T-cells play an essential role in recognizing and clearing viruses from infected tissues. While the peripheral blood T-cell responses among patients with coronavirus disease 2019 (COVID-19) has been well characterized in the recent literature, little is known about the overall repertoire diversity of T-cell responses and SARS-CoV-2-specific T-cell breadth and depth across tissues in patients with severe COVID-19. To fill this knowledge gap, we evaluated the T-cell immune repertoires using bulk sequencing of multiple tissue samples from a cohort of fatal COVID-19 cases.

Methods

Lungs, thoracic lymph nodes and spleens were collected at autopsy from a cohort of 44 patients who died with or from COVID-19. DNA was isolated from paraffin embedded tissues fixed with an ethanol buffer and from peripheral blood mononuclear cells (PBMCs) collected perimortem. T-cell receptor beta (TCRb) sequencing was performed using the Adaptive ImmunoSeq platform and the SARS-CoV-2-specific T-cell response was quantified by exact matching of the TCRb sequences with those reported in the ImmuneCODE and VDJdb databases.

Results

Significantly lower T-cell clonality and higher numbers of unique T-cell rearrangements were observed in lymph nodes compared to the lung tissues and PBMCs across all patients, indicating higher T-cell diversity in the lymph nodes. Clonal expansion was greatest in the PBMCs and least in the lymph node tissues. Pearson correlations between age and SARS-CoV-2 specific T-cell depth, which were controlled for gender and the number of days between onset and death, varied significantly across tissue compartments in both magnitude and directionality. We observed a strong positive correlation (0.35, p< 0.05) between the SARS-CoV-2 specific T-cell depth and older age in the lymph node samples, that was in contrast with an opposite trend in the PBMCs (-0.52, p< 0.001).Figure 1:Lymph node tissues had increased T-cell counts (clone_count: color scale) and increased unique T-cells (clonotype_count: circle size) when compared to PBMCs and lung tissues.Figure 2.PBMC and lung samples have increased clonality (sample_clonality: circle size) and max frequency for the immunodominant clonotype (max_frequency: color scale) when compared to lymph node tissues.

Conclusion

The higher depth of SARS-CoV-2 specific T-cells within lymph nodes of older patients that was not observed within circulating PBMCs suggest a deficit of translocation of virus-specific T cells from the site of antigen presentation to circulation and the site of infection, with implications for the increased severity of disease observed in older patients with COVID-19.

Disclosures

All Authors: No reported disclosures
319. Infectious disease healthcare utilization and outcomes of patients discharged to skilled nursing facilities on parenteral antibiotic therapy
Authors: Bailey Rosemary C , Crnich Christopher J , Jolles Sally , Furuno Jon P , Noble Brie , Langenstroer Madeline C
Published: November 2023

Background

Hospitalized patients are frequently discharged to a skilled nursing facility (SNF) for parenteral antibiotic therapy (PAT). While there are studies describing the healthcare utilization and outcomes of individuals receiving post-hospital PAT in non-institutional settings, characterization of the PAT experience among SNF patients remains limited. To address this gap in knowledge, we conducted a retrospective cohort study of hospitalized patients discharged to a SNF on antimicrobial therapy.

Methods

Health records of patients (age ≥18 years) hospitalized in a single hospital who were discharged on systemic antibiotics to a SNF from 1/1/2016 - 12/31/2018 were reviewed. Subjects who received an inpatient ID consultation and were discharged on PAT were included. Information captured included patient demographics, diagnoses, discharge antibiotic regimen and timing, post-discharge encounters, 90-day hospital readmissions, and losses to follow-up. This study was approved by the Institutional Review Board with a waiver for informed consent.

Results

155 patients meeting the inclusion criteria were identified. Post-discharge follow-up with the ID Service was not recommended for 19 patients (12.3%). Patients who followed-up post-discharge had a total of 264 sub-specialty provider (mean: 2.8/patient; range: 0-13) and 170 ID provider (mean: 1.7/patient; range: 0-5) face-to-face encounters within 90 days of discharge. Average time to ID clinic follow-up was 3.2 weeks (range: 1-6 weeks). ID clinic nursing staff conducted 1373 telephone encounters (mean: 13.9/patient; range, 3-40) with SNF nursing staff within 90 days of discharge. The 90-day hospital readmission rate was 37% (36/101 patients) and 47% of readmissions were ID-related. The 90-day mortality rate was 9%; 2 patients died before and 7 after outpatient follow-up was established.

Conclusion

ID clinic follow-up of patients discharged to a SNF on PAT was infrequent, but their care entailed a higher volume of telephone care coordination, and they experienced higher readmission rates relative to patients receiving PAT in ambulatory settings. Further studies to better understand if these findings are driven by patient factors or issues related to SNF care practices are needed.

Disclosures

All Authors: No reported disclosures
320. Heterogeneity in Clinical Presentations of Sepsis
Authors: Biebelberg Brett , Rhee Chanu , McKenna Caroline S , Klompas Michael
Published: November 2023

Background

Sepsis treatment protocols stipulate a uniform care plan for all patients with possible sepsis. Sepsis clinical criteria, however, may capture a wide spectrum of illnesses. We sought to elucidate the heterogeneity of sepsis by characterizing the breadth of infection types, organ dysfunctions, and their differential outcomes in a large cohort of sepsis patients.

Methods

We identified all adults admitted via the ED to 5 Massachusetts hospitals from 2015-2022 with possible sepsis, defined as suspected infection (blood culture orders and intravenous antibiotics) and organ dysfunction using CMS SEP-1 thresholds (drop in systolic blood pressure [SBP] ≥ 40mmHg or hypotension, elevated lactate, invasive or noninvasive ventilation, elevated creatinine or bilirubin, low platelets, or elevated INR/PTT). We identified infection sources using present-on-admission ICD-10 diagnosis codes and analyzed the frequency and mortality of each combination of infection site and organ dysfunction.

Results

The cohort included 74,609 patients with suspected sepsis: median age 67 [IQR 55-79], 47% female, 24% non-white, 36% hypertension, 33% liver disease, and 28% chronic pulmonary disease. The overall in-hospital mortality rate was 9%. Patients varied widely in sources of infection (e.g. 33% pulmonary, 23% genitourinary, 13% intra-abdominal, and 1% obstetric/gynecologic) and organ dysfunctions (e.g. 57% drop in SBP ≥ 40mmHg, 9% hyperbilirubinemia, and 6% thrombocytopenia). Similarly, mortality rates varied from 3-13% across infection types (Figure 1) and from 3% (drop in SBP alone) to 27% (invasive ventilation) across organ dysfunctions (Figure 2). Combining infection types and organ dysfunctions further extended the spectrum of mortality from 0% for obstetric/gynecologic infections with thrombocytopenia to 35% for bacteremia with elevated INR or PTT (Figure 3).Figure 1:Scatter plot of frequency vs mortality of infectious sources in patients presenting with suspected sepsisFigure 2:Scatter plot of frequency vs mortality of organ dysfunction patterns in patients presenting with suspected sepsisFigure 3:Heat map describing mortality rates for each combination of infectious source and organ dysfunction in patients with suspected sepsis

Conclusion

Sepsis encompasses a wide spectrum of illnesses including multiple infection sites and organ dysfunctions that vary in crude mortality rates from 0-35%. The heterogeneity of sepsis begs the question whether “one-size-fits-all” bundles are suitable. Care tailored to each patient’s presentation may be more appropriate.

Disclosures

Chanu Rhee, MD, MPH, Cytovale: Advisor/Consultant|Pfizer: Advisor/Consultant|UpToDate, Inc.: Honoraria Michael Klompas, MD, MPH, UpToDate, Inc.: Royalties for chapters on pneumonia
322. Improving Assessment of Beta-Lactam Allergies by Embedding a Questionnaire in Best Practice Advisory Alerts Across a Large Health System
Authors: Boger Michael S , Boger Michael S , Jaffa Rupal K , Kiliany Rebecca , Shah Ekta , Morris Lee , Davidson Lisa
Published: November 2023

Background

Penicillin (PCN) allergy is commonly reported. Yet most patients labeled allergic can tolerate beta-lactams (BLs), the antibiotics of choice for many infections. Documentation of reaction details is important to identify low risk patients who can safely receive BLs, but it is often incomplete. A May 2018 point prevalence study from the electronic medical record (EMR) using a one-week sample of Atrium Health Greater Charlotte Market (AH) PCN allergy patients showed that 52% had no reaction documented.

Methods

This was a retrospective, observational study in thirteen hospitals in the AH system. To improve BL allergy assessment, a BL allergy questionnaire was developed during the launch of a new AH wide EMR. During the initial roll-out, a best practice advisory (BPA) fired for nursing when entering a BL allergy, prompting a link to a separate BL allergy questionnaire for nursing completion. After all sites were live, we assessed questionnaire completion rates. During the optimization phase, the questionnaire was incorporated directly in the BPA and simplified from ten to three questions, allowing completion in one step (Fig 1). The answers are then automatically sent to flowsheets where they are available for reference and feed into assessment algorithms that provide the allergy level of risk and clinician treatment guidance upon antibiotic order entry (Fig 2). The BPA fires daily as a reminder until questionnaire completion.Figure 1.Beta-Lactam Allergy Questionnaire Best Practice Advisory (BPA).Figure 2.Beta-Lactam Allergy Assessment Algorithm.

Results

Pre-optimization: Over a ten month period from December 2021 through October 2022, 4118 inpatient questionnaires were completed. Beginning in August 2022, when all facilities were live on the new EMR, the average monthly questionnaire completion was 833 (Fig 3). Post-optimization: In November 2022, completion increased 38.9%, resulting in an additional 4743 questionnaires over four months (average of 1186 per month). The number of questionnaires completed thereafter decreased as the number of patients with previously completed questionnaires increased.

Conclusion

The creation of a targeted BL allergy questionnaire in the EMR improved BL allergy documentation across a large, diverse health system. The effect was enhanced through workflow optimization incorporating the questionnaire into a one-step BPA.

Disclosures

All Authors: No reported disclosures
326. Meeting an unmet need - impact of a Complex Fungal Infection Clinic in the UK
Authors: Dominic Catherine , Houston Hamish , Das Abhishek , RH Stone Neil
Published: November 2023

Background

The WHO recently set out priority fungal pathogens of global importance which were previously neglected in terms of awareness & funding(1). Accurate diagnosis of fungal infection is a challenge & mortality remains high(2) as expertise and dedicated mycology services are lacking globally. Our centre provides one of the UK’s first complex fungal infection clinics, established in 2019. We sought to describe the patients attending this clinic, as a step towards understanding the landscape of clinical mycology in the UK.

Methods

Electronic health record systems were searched for all patients attending our clinic over 4 years from 01/04/19-01/04/23. Patients referred for consideration of a fungal diagnosis were included in the analysis. Invasive fungal infections (IFIs) were classified as per EORTC/MSGERC guidance.(3)

Results

80/407 patients attending our clinic were referred for consideration of a fungal diagnosis. 31 (39%) were male. Median age was 53 (IQR 38-62). Most referrals (59/80; 74%) were received from within our institution. 41 (51%) had a fungal diagnosis confirmed prior to review. 28 were treated for invasive fungal infections (IFIs), 9 for chronic mycoses (including 5 chronic pulmonary aspergillosis & 2 mycetoma), 28 for superficial mycoses (20 recurrent mucocutaneous infections & 8 onychomycoses) & 15 had no evidence of fungal infection. Of the IFI: 16 were proven; 8 probable; 2 possible IFI & 2 did not meet diagnostic criteria. 7 IFI were caused by Aspergillus, 8 by Cryptococcus & 2 each by Coccidiodes, Candida & Histoplasma. The IFIs mainly affected the upper & lower respiratory tract (17/28). 20/80 (25%) were immunosuppressed (commonest causes: diabetes; HIV; steroids; malignancy & chemotherapy). On average (median), patients visited clinic 4 times (IQR 2-7) & received 2 different antifungal drugs (IQR 1-3). The most common side-effects prompting a change in therapy were visual changes, rash & diarrhoea.

Conclusion

Our data illustrate the need for dedicated follow-up for patients with complex fungal infections. With several new antifungal drugs currently undergoing clinical trials, complexity in therapeutic decision-making will only increase.(4) Establishing centralised complex fungal infection clinics helps to build diagnostic & clinical capacity in mycology.

Disclosures

Hamish Houston, BA MBBCh, Gilead Sciences: Grant/Research Support Neil RH Stone, MD PhD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Pfizer: Honoraria|Shionogi: Honoraria
328. One-Day Holiday: An Approach to Managing Daptomycin-Induced CK Elevations in OPAT
Authors: Fabricio Julia B , Swartwood Michael , Oosterwyk Teresa M , Schranz Asher J , Farel Claire E , Mavrogiorgos Nikolaos , Bowman M C , Kinlaw Alan C , Boerneke Renae
Published: November 2023

Background

Daptomycin can be ideal for outpatient parenteral antimicrobial therapy (OPAT) due to its once-daily dosing, tolerability, and lack of nephrotoxicity compared to vancomycin. Though infrequent, skeletal myopathy with associated elevation of serum creatinine kinase (CK) is a clinically significant adverse effect associated with daptomycin. Risk factors associated with CK elevations include initial dose, obesity, chronic kidney disease, and statin use.

Based on a case series by Burdette et. al, the UNC OPAT Program manages asymptomatic mild-to-moderate CK elevations by either a one-day dose holiday with continuation of the same dose or one-day daptomycin holiday followed by dose reduction. We assessed the effectiveness of this strategy for allowing continuation of daptomycin in our patient population.Figure 1:Daptomycin and CK Elevations FlowchartTable 1:Baseline Demographics

Methods

A total of 396 patients received daptomycin in the OPAT Program from March 2015 to January 2023. We analyzed associated baseline risk factors for patients with CK elevations above 500 U/L and management strategies (e.g., one-day holiday, dose reduction, and/or drug discontinuation). CK elevations were defined as mild (500-999 U/L), moderate (1000-1999 U/L), or severe (≥ 2000 U/L).

Results

Of the 396 patients on daptomycin, 36 (9%) experienced a CK elevation > 500 U/L. 34 (94%) patients required further management. 58% of patients were asymptomatic, with 55% having mild CK elevation. Most reported symptoms were muscle/joint pain. On average, CK elevations occurred 18 days (± 9) into therapy, with a shorter time to CK elevation for severe (11 days ± 2) and moderate elevation (14 days ± 6). Lab abnormalities were managed within one day. Of the 7 patients that had a one-day holiday only, 5 experienced CK improvement. Of the 8 patients with a one-day holiday + dose reduction, 6 showed CK improvement. No patient with dose reductions had readmission during treatment course and one had infection recurrence within 90 days.

Conclusion

The one-day holiday +/- dose reduction adjustment strategy for management of CK elevations allowed for continuation of daptomycin without compromising treatment or leading to hospital readmission. Timely evaluation of safety labs and dose adjustment strategies are key in managing CK elevations for OPAT patients receiving daptomycin.

Disclosures

Asher J. Schranz, MD, MPH, WoltersKluwer: Honoraria Alan C. Kinlaw, PhD, Genentech: Grant/Research Support
331. Emphasizing the O in OPAT: A Pathway for Ambulatory Outpatient Parenteral Antimicrobial Therapy (OPAT) Initiation from an Academic Infectious Diseases Clinic
Authors: Hillenbrand Molly , Yarrington Michael E , Funaro Jason , Shroba Jenny , Dicks Kristen
Published: November 2023

Background

In response to rising inpatient costs, health care systems are investigating mechanisms to avoid unnecessary admissions and reduce inpatient length of stay. Outpatient parenteral antimicrobial therapy (OPAT) provides a pathway for patients to receive intravenous antimicrobials at home or in a skilled nursing facility (SNF); however, admission is often required for OPAT initiation. Our interdisciplinary OPAT team developed a process to initiate OPAT directly from our infectious diseases (ID) clinic (Figure 1). We report our single-center experience and patient outcomes.

Figure 1. Process map for ambulatory outpatient parenteral antimicrobial therapy (OPAT) initiation. ID, Infectious diseases; PICC, peripherally inserted central catheter.

Methods

We conducted a consecutive case series review of patients who completed OPAT episodes started directly from our ID clinic between July 1, 2022, and March 31, 2023. Patients with a history of solid organ transplant, hematologic malignancy, or end stage renal disease on hemodialysis are not managed by our formal OPAT team and were thus excluded. We reviewed patient demographics, clinical characteristics, and adverse events while receiving OPAT. Admission rates for inpatient and outpatient cohorts were compared using Pearson Chi Square analysis.

Results

Thirty-seven patients were started on OPAT directly from our ID clinic during the study period (Table 1, Figure 2). Most patients had intravenous access placed by a vascular access nurse in our clinic, and all received OPAT at home. The 30-day admission rate for this cohort was significantly less than OPAT patients who were discharged from the hospital during the study period (157/684 vs 1/36, p=0.004). One patient in this series was admitted to the hospital for persistent prosthetic joint infection requiring repeat surgical intervention. Serious OPAT-related adverse events in this cohort were less than previously published rates (Table 2), and line complications were addressed in our clinic in 3/6 cases, avoiding emergency department visits.Table 1.Demographic and clinical characteristics of 37 patients started on OPAT directly from ID clinic. IQR, interquartile range; PICC, peripherally inserted central catheter.Figure 2.Indications for OPAT in 37 patients started on OPAT directly from ID clinic. CNS, central nervous system; SSTI, skin and soft tissue infection.Table 2.OPAT-related adverse events in 37 patients started on OPAT directly from ID clinic.

Conclusion

This case series demonstrates that OPAT initiation directly from an ID clinic is feasible and safe, with lower admission and complication rates than patients discharged from acute care settings on OPAT. A robust ambulatory OPAT program with an interdisciplinary OPAT team can result in substantial cost savings for healthcare systems.

Disclosures

Kristen Dicks, MD, UpToDate: Advisor/Consultant
336. A 6-Sigma Approach for Follow-up Evaluation of Outpatient Parenteral Antimicrobial Therapy (Project SAFE-OPAT) To Improve Documentation and Post-Discharge Care
Authors: Keri Vishakh C , Ali Sajjad , Elattma Ahmed , Monday Lea M
Published: November 2023

Background

Outpatient Parenteral Antimicrobial Therapy (OPAT) is challenging to implement safely and difficult for infectious diseases (ID) physicians to monitor in centers without a dedicated OPAT staff. We utilized a 6-Sigma framework to evaluate our OPAT process and define opportunities for improvement.

Methods

In a retrospective cohort study, we screened 5 months of ID consult data for patients who left on OPAT from an urban hospital system (Fig 1). Primary outcome was incidence of adverse event (AE), a composite of either emergency department (ED) visit or all-cause 30-day readmission. Clinical characteristics and completeness of ID documentation were compared between patients with and without an AE. Complete documentation included antibiotic dose, duration, stop date, and a scheduled ID appointment. We simultaneously conducted a 6-sigma analysis involving stakeholders (physicians, case managers, nurses) in focus groups, to generate a process map, Ishikawa diagram, 5-Why’s analysis, and identify heterogeneity in our OPAT process (Fig 2).

Results

Fifty of 441 patients (11.3%) were discharged on OPAT and incidence AE was 30%. Neither type of infection (Fig 3), nor demographics, clinical characteristics, or discharge location differed between groups (Table 1). Only half (50%) of the patients had complete documentation. Median time from discharge to clinic was 21 days, however, AE’s occurred in a median time of 12 days. Patients without an AE were more likely to have been seen in the clinic post-discharge (51% versus 20%, p=0.039). ID clinic appointments were made for 60% of patients, with a show rate of 63%. (Fig 4). Two additional unscheduled patients initiated their own visit (Fig 4). The 6-Sigma analysis identified process heterogeneity at discharge location and over-reliance on human memory for complete documentation. Interestingly, focus groups revealed numerous assumptions not supported by the objective data (Fig 5 in conclusion).

Conclusion

Almost 1 in 3 patients leaving on OPAT experienced an adverse event. A 6 Sigma analysis identified heterogeneity in our process and incorrect assumptions among stakeholders (Fig 5). Next steps should focus on improving ID documentation and ensuring all patients leaving on OPAT have an ID clinic visit scheduled within 14 days after discharge.

Disclosures

All Authors: No reported disclosures
338. ChatGPT Conveys Incorrect Information about the FDA’s Antibiotic Boxed Warnings
Authors: Linfield Rebecca , Parsonnet Julie
Published: November 2023

Background

Chat Generative Pre-training Transformer (ChatGPT) is a popular artificial intelligence-based chatbot that rapidly provides responses to online inquiries. As a language-processing – rather than a scientific – tool, ChatGPT does not guarantee accuracy. The United States Food and Drug Administration (FDA) labels medications with significant risk of serious or life-threatening adverse effects with boxed warnings (BW). We sought to assess the accuracy of ChatGPT regarding FDA BW for antibiotics.

Methods

FDA labels for commonly-used antibiotics were categorized through the DailyMed database of the National Library of Medicine (Table 1). ChatGPT-3.5 was then queried regarding FDA BWs using the following query: “Are there any boxed warnings on the FDA label for XX [medication] and if so, what are they?” Responses were sorted into 3 categories:(1) “Matching”: ChatGPT accurately reported both existence and content of BW or its absence;(2) “Inaccurate”: ChatGPT accurately reported a BW but erred on some aspects of the content; and(3) “Incorrect”: ChatGPT misidentified existence of BW, or listed incorrect adverse effects (AE)Table 1:FDA Boxed Warnings for Commonly Used Antibiotics

Results

Of the 41 antibiotics queried, 9 have FDA BWs and ChatGPT correctly identified the existence of all 9. However, ChatGPT correctly matched the AE of the FDA BW in only 3 instances (33%); in five instances (56%), ChatGPT listed inaccurate AEs (either under- or overinclusive) and in one (11%), ChatGPT listed an incorrect AE. For the 32 antibiotics without an FDA BW, ChatGPT reported that 23 (72%) had a BW (Figure 1). Figure 2 provides some examples of incorrect ChatGPT claims regarding AEs.Figure 1:ChatGPT Responses about FDA Boxed WarningsFigure 2:Examples of Incorrect ChatGPT claims

Conclusion

ChatGPT reported inaccurate and incorrect information about FDA BW for antibiotics. Clinicians should be aware of this new source of information for patients.

Disclosures

All Authors: No reported disclosures
346. Evaluation of the Safety Profile of Cefazolin Monotherapy in Outpatient Parenteral Antibiotic Antimicrobial Therapy at a Large Academic Medical Center
Authors: Poux Nicolas , Gillett Eric M , Franklin Catherine , Estano Mark J , Dewan Charles , Sheedy Kate , Dionne Brandon , Kubiak David W , Pearson Jeffrey C , Chan Brian T
Published: November 2023

Background

The Infectious Diseases Society of America recommends serial safety lab monitoring during outpatient parenteral antimicrobial therapy (OPAT) to assess treatment response and prevent adverse events. However, these recommendations do not address the safety profile of specific antimicrobial agents or the ideal frequency of monitoring. Previous studies, using cohorts of fewer than 300 patients, report adverse event rates of less than 5% with outpatient cefazolin. It is possible that serial lab monitoring for patients on cefazolin monotherapy may represent unnecessary work and increase costs with minimal patient benefit.

Methods

A retrospective chart review was performed on patients treated with cefazolin monotherapy in the OPAT program of Brigham and Women’s Hospital (Boston, MA, USA) from February 2018 to February 2023. Data from weekly safety labs were examined during OPAT for the following abnormalities: change in creatinine (absolute increase of 0.5 mg/dL or relative increase ≥50%), ALT > 100 units/L, neutropenia (absolute neutrophil count < 1000 cells/mm3), eosinophilia ( >500 cells/mm3), and thrombocytopenia (< 100K/uL or relative decrease ≥50%). Other treatment complications adjudicated from chart review included antibiotic treatment changes, readmission, or mortality during OPAT.

Results

Among the 420 patients receiving cefazolin in OPAT, the median age was 62 (IQR: 49-71) years; 168 patients (40%) were women, and 62 (15%) were referred from oncology or transplant services. Twenty-four (6%) patients had at least one lab abnormality. Of these, 13 (3%) required a treatment change or had readmission or death. Eight (2%) cases were related to a lab abnormality, while five were due to other factors either unrelated to antibiotic therapy or apparent on clinical examination (e.g., rash).

Conclusion

In an OPAT program at a large academic medical center, weekly lab monitoring altered clinical decision-making for 2% of patients on cefazolin monotherapy. It may be reasonable to reduce the frequency of or eliminate routine lab monitoring for these patients to reduce the cost of healthcare services. Future studies are indicated to evaluate the clinical impact of less frequent lab monitoring for OPAT patients on cefazolin monotherapy.

Disclosures

David W. Kubiak, PharmD, BCPS, BCIDP, FIDSA, Astellas Pharma, Inc.: Advisor/Consultant|AVIR Pharma Inc: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant|Shionogi Inc: Grant/Research Support
349. The impact of Vancomycin dosing by area under the curve over minimal inhibitory concentration (AUC/MIC) versus Trough levels on cumulative Vancomycin dosage and incidence of Acute Kidney Injury (AKI) in patients admitted to intensive care units (ICU)
Authors: Sahu Aniruddha , Wang Kevin K , Jurasinski Philip , Kulkarni Salil , Weihs Sayo , Mizusawa Masako , Bamberger David
Published: November 2023

Background

Higher Vancomycin trough levels (15-20 mcg/ml) are associated with increased risk of AKI. IDSA recommends dosing Vancomycin as per AUC/MIC reduces the risk of nephrotoxicity. The aim of this study was to determine if AUC/MIC dosing could reduce the incidence of nephrotoxicity patients in admitted to intensive care unit (ICU). This has not been previously studied.

Methods

This was a retrospective pre and post chart review study including all admitted patients to ICU at Truman Medical Center Hospital Hill, Kansas City, Missouri from 10/1/2020 to 10/1/2021. The pre intervention period (trough monitoring) was 10/1/2020-3/29/2021.The post intervention period was 4/1/2021-10/1/2021, included patients who received Vancomycin dosing via using a Bayesian derived AUC monitoring software program targeting AUC of 400-600 mg*hour/L (Insight Rx). All patients who were admitted to ICU and received Vancomycin for >48 hours were included. Exclusion criteria includes Vancomycin use for < 48 hours, end stage renal disease and who received continuous renal replacement therapy within 48 hours of starting Vancomycin.

Results

119 patients received Vancomycin dosing by AUC/MIC and 122 patients by Vancomycin trough. Patients received 23.51 ± 2.13 mg/kg/day(mean ± standard error) Vancomycin in AUC/MIC and 25.28 ± 1.71 mg/kg/day in trough group (p = 0.18). The incidence of AKI was 25.21%(n=30) in AUC/MIC group and 17.21%(n=21) in trough group (p = 0.13). Vancomycin was used for 5.61 ± 0.68 days in AUC/MIC group and 4.92 ± 0.48 days in trough group (p = 0.10). The incidence of AKI in patients who received concomitant intravenous contrast was 26.22%(n=16) in AUC/MIC group and 10.90%(n=6) in trough group (p = 0.04*). Average length of stay (LOS) in ICU was 11.56 ± 2.65 days in AUC/MIC group and 8.66 ± 1.61 days in trough group (p = 0.06). All-cause mortality during hospitalization was 29.41%(n=35) in AUC/MIC group and 22.13%(n=27) in trough group (p = 0.20). AKI was noted in 19.82% patients receiving Piperacillin tazobactam and Vancomycin versus 22.4% receiving Vancomycin without Piperacillin tazobactam(p = 0.63).

Conclusion

There was no difference in cumulative vancomycin dose, incidence of AKI, LOS and All-cause mortality during the hospitalization while using Vancomycin dosing by AUC/MIC vs trough in ICU patients.

Disclosures

All Authors: No reported disclosures
350. Unnecessary viral blood tests reduction and costs saving by using an automated test request blocking system
Authors: Rahamim-Cohen Daniella , Valinsky Lea , Beit Or Anat , Shamai-Lubovitz Orna , Fisher Moshe , Azuri Josef , Ben David Shirley Shapiro
Published: November 2023

Background

As demands and costs rise across all aspects of healthcare, blood tests form a significant part of existing health expenses. Laboratory analysis provides a vital tool for the evaluation and monitoring of patients with suspected infectious diseases in the community, but are occasionally ordered without accurate clinical indications, resulting in unnecessary expense, workload and patient distress. Here we examined the economic utility of integrating a rule engine system, used in this context to block unnecessary infectious disease laboratory tests.

Methods

An automated blocking system for blood tests, including tests for viral diseases, was designed and implemented within the electronic medical record (EMR) by Maccabi Healthcare Services, a health maintenance organization in Israel, serving over 2.5 million members, nationwide. The system blocks requests for tests identified as unnecessary, usually based on a previous result. Specifically, the system blocks blood tests for the following viral diseases: Hepatitis C viral load and serology for: EBV, CMV, Rubella, Varicella Zoster and Hepatitis B. Upon provider request, a non- authorized test can be re-evaluated by an infectious diseases specialist (Figure 1). Test costs were assessed using the standard Israel Ministry of Health price list in Israeli currency (New Israeli Shekel-NIS) and are expressed in 2023 USD (1$=3.62 NIS, according to the currency exchange rate on May 2, 2023).Figure 1:Automated test request blocking system workflow. EMR Electronic Medical Record, ID Infectious Disease

Results

During 2022, 407,403 requested viral blood tests were recoded (Table 1). Of them, 302,322 (74.2%) were automatically approved. Of those blocked, only a small proportion were requested for further authorization (between 0.15-1.1%). The calculated savings for declined tests is approximately 5.8 million USD.

Conclusion

This automated authorization system for certain viral blood tests resulted in an improved clinical decision process by blocking unnecessary tests and led to substantial monetary saving without sacrificing physician autonomy.

Disclosures

All Authors: No reported disclosures
353. Outpatient parenteral antimicrobial therapy (OPAT) in managing vertebral osteomyelitis
Authors: Villacorta Cari Evelyn , Young Michael , Clemons Alisha , Logan Ashley , Mynatt Ryan , Soria Jaime
Published: November 2023

Background

The outpatient parenteral antimicrobial therapy (OPAT) program was formally established at the University of Kentucky in 2019 to coordinate and monitor home-delivered antimicrobial treatment. This analysis describes the epidemiologic, microbiologic features, and outcomes of subjects diagnosed with vertebral osteomyelitis referred to the OPAT program.

Methods

A cross-sectional study was conducted; we analyzed the data collected during the OPAT program evaluation from July 2019 to October 2022. The data were collected and managed using REDCap electronic data capture tools hosted at the University of Kentucky.

Results

The analysis included 411 subjects diagnosed with vertebral osteomyelitis. referred to the OPAT program. The median age was 51 years old (range: 22-91), and 254 (61.8%) were male. Active or previous history of intravenous drug use (IVDU) was reported in 193 (47.1%), being the most recent use within the last 30 days reported in 142 (74.0%). Admission to the intensive care unit (ICU) was documented in 110 (27.0%) subjects; mainly due to infection related to the OPAT indication; the median Charlson Comorbidity Index score was 2 (IQR: 0-4). The median duration in the OPAT program was 18 (IQR: 11-34) days. The distribution by spinal segment was as follows 115 (28.0%) in the lumbar spine, 75 (18.2%) in the thoracic spine, 58 (14.1%) in the cervical spine, 57 (13.9%) in the sacral and sacrococcygeal spine, more than two segments in 12 (2.0%) subjects, and unspecified in 94 (22.9%) subjects. The most common pathogen isolated was Staphylococcus aureus in 182 (44.3%) subjects, followed by Streptococcus spp in 19 (4.6%). Among gram-negative bacterium, Serratia spp and Pseudomonas aeruginosa were the more prevalent pathogens, 18 (4.4%) and 15 (3.6%), respectively, mainly when the sacrococcygeal spinal segment was compromised. Fungal infection was documented in 13 (3.1%) subjects. The most common antimicrobial used was daptomycin, followed by vancomycin in 97 (23.6%) and 78 (19.0%) subjects, respectively. In this cohort, , the overall mortality rate was 2.2%.

Conclusion

The OPAT program is a convenient and safe alternative for treating vertebral osteomyelitis that requires a prolonged course of intravenous antimicrobial treatment.

Disclosures

All Authors: No reported disclosures