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Abstract Background Bacterial blood stream infection (BSI) is a leading cause for mortality and morbidity in the pediatric solid organ transplant recipient population. This systematic review aims at pooling global data from the leading transplant institutions to identify the overall prevalence and risk factors associated with bacterial BSI and the most common causative organisms. Methods A systematic review of PubMed and OVID databases was conducted for the past 20 years. Initial search from both databases had a yield of 252 unique articles which were reviewed independently by two authors. Data related to demographics, prevalence, organisms and risk factors were extracted from the articles and subsequently analysed. The systematic review was registered on PROSPERO (ID: CRD42023403206). The PRISMA flow diagram visually summarises the screening process Results A total of 14 articles were included from the United States of America, France, Italy, Thailand, Japan, Spain and Korea. A total of 4215 liver transplants were included in the final analysis. The overall prevalence of BSI in pediatric liver transplant patients was 23.5% with the highest prevalence reported in Japan (39.5%) and lowest in the USA (18.7%). Mean age of the patients was 25 months and 54% were females. The most common organisms reported were Staphylococcus epidermidis at 22.8% followed by Enterococcus species (16.6%), Klebsiella species (11.9%) and Escherichia coli (11.4%). Among the risk factors studied, postoperative biliary complications, past medical history of biliary atresia and younger age were the risk factors most associated with BSI. Prevalence of bloodstream infections (BSI) post pediatric liver transplant in included countries. Bacterial organisms isolated in blood cultures in pediatric post liver transplant patient with a bloodstream infection. Conclusion Bacterial BSI post pediatric liver transplantation occurs with high prevalence. Further studies need to be conducted to better define risk factors for BSI and determine the best empirical antibiotic management for BSI in this population as the distribution of organisms varies greatly from otherwise healthy pediatric patients. Disclosures All Authors: No reported disclosures

Abstract Background Definition of the microbiology of pleural space infection has been challenging due to the poor yield of conventional culture, a challenge that has led to recommendations for broad spectrum antimicrobial therapy for these infections. Since August 2019, we have offered a 16S ribosomal RNA gene PCR assay followed by Sanger or next generation sequencing, or reported as negative, depending on the PCR signal strength (e.g., crossing point) in clinical practice at Mayo Clinic. Methods Here, we describe the microbiologic and clinical findings of 57 pleural fluids testing positive by 16S rRNA gene PCR/sequencing from August 2020 to January 2023. Demographic data and clinical features, and results of pleural fluid and blood cultures were recorded. Analysis was performed using SAS software version 9.4 (SAS Inc). Results Median patient age was 63 years (range 5-83 years) and 75% were men. Pleural space infection was community-acquired in 84%. The most frequent symptom was dyspnea (80%), followed by chest pain (52%). 89% of patients had received antibiotics in the two weeks preceding specimen collection. Radiological consolidation was observed in 63% and pleural fluid was loculated in 58%. Pleural fluid and blood cultures were positive in 32 and 11%, respectively. The microbiology found with the sequencing assay is shown in the table. 23/57 (40%) detections were polymicrobial. Fusobacterium nucleatum group and/or Streptococcus intermedius were detected in 31/57 (54%) cases [including 28/48 (58%) in the subset with community-acquired infection], with additional facultative and/or anaerobic species in various combinations also found in 17/31 (55%) of these cases. Conclusion Based on analysis of pleural fluid using a targeted metagenomic sequencing assay in clinical practice, the most frequent organism profile involved in community-acquired pleural space infection is a combination of Fusobacterium nucleatum group and/or Streptococcus intermedius, with or without other normal microbiota, a grouping for which we propose the term FuSion (Fusobacterium nucleatum group, Streptococcus intermedius and oral normal microbiota). Disclosures Eva Carmona, MD, boehringer ingelheim: Advisor/Consultant Øyvind Kommedal, n/a, Pathogenomix inc.: Advisor/Consultant|Pathogenomix inc.: Stocks/Bonds Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant

Abstract Background Native joint septic arthritis (NJSA) is diagnosed by synovial fluid analysis to evaluate for evidence of infection but may be definitively established by a positive gram stain or culture. Antibiotics given prior to synovial fluid sampling have been described to alter cell count, gram stain, and culture results and are conventionally deferred until after arthrocentesis to optimize diagnostic yield. However, there is limited data on the impact of preoperative antibiotic therapy on operative culture yield in the diagnosis of NJSA. Methods Following IRB approval, we reviewed medical records of adults diagnosed with NJSA who underwent surgical intervention at Mayo Clinic facilities from January 2012 to December 2021. The effect of preoperative antibiotic therapy on operative culture yield was evaluated through a paired analysis of preoperative and operative cultures results utilizing logistic regression along with generalized estimating equations (GEE) to account for correlations of multiple measurements on the same subject. Results A total of 299 patients with NJSA of 321 joints with the accompanying characteristics who underwent surgery met study criteria (Table 1). Joint distribution, microbiology, and antibiotic administration are outlined in Table 2. Among those treated with preoperative antibiotics, there was a significant decrease in yield between preoperative and operative cultures (68.0% to 57.1%, p < .0001), whereas in patients without preoperative antibiotic exposure, there was an increase in yield (60.9% to 67.4%, p = 0.244; Figure 1). Logistic regression analysis revealed that preoperative antibiotic exposure was more likely to decrease operative culture yield as compared to non-exposure (change, -10.9% vs. +6.5%; p = .006). Secondary analyses restricted to individuals who received preoperative antibiotics revealed that an increasing number of doses and earlier administration of initial antibiotic therapy were associated with lower rates of operative culture yield (Figure 2). Joint distribution, diagnostic/microbiologic, and antibiotic administration characteristics of 321 joints in 299 patients with native joint septic arthritis Composite Image 1: Figure 1, 2a/2b Figure 1: Change in Preoperative and Operative Culture Yield with Antibiotic Exposure Figure 2: Effect of Antibiotic Doses and Timing of Therapy on Predicted Probability of Operative Culture Positivity Conclusion In patients with NJSA, preoperative antibiotic exposure resulted in a significant decrease in microbiologic yield of operative cultures as compared to patients in which antibiotic therapy was held prior to obtaining operative cultures. Disclosures Brandon J. Yuan, M.D., American Association of Orthopaedic Surgeons: Board Member|DePuy, A Johnson & Johnson Company: Advisor/Consultant|Mid America Orthopaedic Association: Board Member|Stryker: Advisor/Consultant Gina A. Suh, M.D., Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: IP royalties|Phagelux: Grant/Research Support Aaron J. Tande, M.D., Musculoskeletal Infection Society: Board Member|Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support

Abstract Background Periprosthetic joint infection (PJI) is a devastating complication following joint replacement, associated with morbidity and mortality. Here, we established a clinically representative murine model of knee arthroplasty and determined the ideal bacterial inoculum that would result in PJI without causing significant limb compromise.Figure 1.An example of an uninfected titanium prosthesis osseointegrated into the tibia of a mouse. Methods A titanium tibial prosthesis designed for the murine knee was 3D printed and surgically implanted into the proximal tibia (Figure 1) of 38 C57BL/6 mice. The prosthesis is designed to osseointegrate into the tibia and has a smooth articular surface to allow for immediate weight bearing and range of motion. At the time of surgery, the arthroplasty was inoculated with five inocula of Staphylococcus aureus Xen36, ranging from 29 to 14,000 colony forming units (CFU) (Table 1). Mice were sacrificed at 3 weeks, or earlier if necessary due to infectious sequelae, and the joint tissue, tibia, femur, and prosthesis quantitatively cultured. Results All mice inoculated with 181 to 14,000 CFU developed PJI as did 90% inoculated with 29 CFU. Bacterial loads from joint tissues and tibial prostheses are shown in Table 1. All mice inoculated with 14,000 and 760 CFU had overt findings of infection (abscesses, sinus tracts, significant limb dysfunction) requiring early euthanasia (Table 2). Mice inoculated with 640 CFU had swelling, redness, and small sores in first 3 days, and 1 death, but otherwise appeared well; only 2/9 had a visible abscess at 3-week sacrifice. 2/10 mice receiving 181 CFU had small sores that resolved in the first week; all limbs functioned well prior to sacrifice. Mice receiving 29 CFU had no external evidence of infection, however 9/10 had purulence within the joint at sacrifice. Conclusion This study demonstrates that inoculum size directly impacts clinical manifestations of infection in a murine model of S. aureus PJI. An inoculum of 181 CFU resulted in universal infection without significantly compromising the limb. The ability of this model to create PJI without overt infectious sequela will allow for evaluation of therapeutics, including those locally delivered. Disclosures Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant Nicholas Bedard, MD, Stryker: Advisor/Consultant

Abstract Background Human granulocytic anaplasmosis (HGA) is an emerging tick-borne illness endemic to the northeastern and midwestern United States. Risk factors for the severity of infection, predictors for hospitalization, temporal trends, co-infections, and outcomes are poorly studied. Methods We conducted a retrospective review of HGA at Mayo Clinic, Rochester, between 2011-2021. Cases were identified by positive Anaplasma PCR at our reference laboratory. Variables included patients’ characteristics, symptoms, risk factors for tick-borne illness, laboratory parameters, co-infections, treatment, and clinical outcomes. Results We identified 471 cases with a positive Anaplasma PCR, and 146 cases were included in this interim analysis. Table 1 shows a summary of the baseline characteristics. An increasing annual trend in diagnosis of HGA was noted from 2014 to 2016 with lower rates observed during COVID-19 pandemic (2020 to 2022) (Figure 1). Of the 146 patients, 19 (13%) were immunocompromised secondary to hematologic malignancies, solid organ malignancies, and pharmacological immunosuppression. Frequently reported symptoms included fever (79.5%), malaise (68.5%), chills (51.4%), and myalgia (50%). Tick exposure was documented in 79.2 % of cases. Forty-seven (33%) patients were hospitalized; older patients were more likely to be hospitalized (Table 2). The most common complications among the hospitalized patients included respiratory failure (50%), encephalopathy (44.4%) and renal failure (37.5%). One patient required ICU admission. Twenty-five patients (17.5%) and one patient (0.7%) were co-infected with Lyme and Ehrlichiosis, respectively. Higher rates of leukopenia and thrombocytopenia were associated with mono-infection with Anaplasma (p < 0.001). Follow up data was available for 136 patients; all of them had favorable response to doxycycline.Table 1:Summary of baseline characteristics, labs and treatment.Table 2:Predictors of HospitalizationFigure 1:Annual Trends in Anaplasmosis from 2011-2021. Conclusion Our study demonstrated comprehensive clinical characteristics of patients with HGA. Interestingly, tick exposure history was common, yet most patients did not have other tick-borne co-infections. Furthermore, only a minority of patients developed severe diseases and required hospitalization. The recent decline in cases during the early part of the COVID-19 pandemic is worth further investigation. Disclosures All Authors: No reported disclosures

Abstract Background Twitter has become an invaluable resource for gaining insights into crucial developments in global healthcare communication. The hashtags (#) can be used to categorize tweets and gather conversations on a specific topic or to target a particular audience. Although the prevailing knowledge fund underlines the potential of digital networks to essentially influence the management of infectious diseases (ID), there has been no comprehensive analysis on the user information in the ID Twitter community, nor of the influence this hashtag has generated. The objective of our study was to evaluate the demographic data of #IDTwitter users, discern the most influential members and popular narratives in this realm, and ascertain the impact of the hashtag. Methods Using data from 28th June 2019 and 28th March 2023, an extensive analysis was conducted using the Symplur Signals research analytics tool. The analysis focused on the cumulative number of tweets, impressions, and unique users who shared tweets containing the hashtag #IDTwitter, with users categorized into specific healthcare stakeholder groups. The primary outcome measures were outreach and awareness measured by the number of tweets and impressions. Results The study observed the trends of #IDTwitter over a period of 45 months and found 441,650 tweets were shared by 92,734 users that generated a total of 1,833,037,732 impressions (views). Top five co-occurring hashtags were #IDtwitter, #MedTwitter, #MedEd, #COVID19, #TwitteRx. The top five countries reporting the greatest number of users of this hashtag were The United States of America (48326), Canada (4803), Mexico (3413), India (2759), Australia (2658). Various healthcare stakeholders’ categories were identified and three largest groups of contributors were Doctors (14.55%), Healthcare Providers (7.54%) and Researcher/Academic (3.70%). The top three influencers of this hashtag include two clinical pharmacists and one organization account. Country-wise distribution of Users of #IDTwitter The image shows the geographical distribution of the users who posted tweets containing #IDTwitter were shared (based on the locations at which the posting accounts were registered). Twitter is used worldwide for conversations regarding communicable diseases and their prevention, not only among the general public but also among students and professionals via online chat discussions and virtual rounds. Stakeholders of #IDTwitter Accounting for the percentage distribution of #IDTwitter-posting users in various healthcare stakeholders categories (data derived from Symplur Signals, with the classification being based on information provided in the Twitter biographies of the users- https://help.symplur.com/en/articles/103684-healthcare-stakeholder-segmentation). Twitter has become a quintessential tool for connecting people worldwide, and we can leverage this platform to our advantage by paying close attention to the topic and content of hashtag exchanges to combat misinformation related to matters like antibiotic usage or any epidemic infection on social media platforms. Top Co-occurring Hashtags The hashtags that generally appear alongside of #IDTwitter could provide an insight regarding the popular discussions involving #IDTwitter. Conclusion Our findings indicate that there is considerable interest in using #IDTwitter to promote relevant content and engage a geographically diverse audience. It underscores the vitality of professional voices in combating misinformation and we could definitely leverage this 'viral' hashtag for our advantage. Disclosures All Authors: No reported disclosures

Abstract Background Non-diphtheriae Corynebacterium spp. are important human pathogens responsible for a broad spectrum of clinical syndromes. Data on species-specific susceptibility patterns is limited. In this study we aim to study these susceptibility patterns over time and summarize the species-specific resistance profile that could be used by clinicians to guide therapeutic decisions. Methods We conducted a retrospective review of all the Non-diphtheriae Corynebacterium isolates that were submitted for antimicrobial susceptibility testing (AST) between January-2012 and February of 2023 to our reference lab. Results A total of 1925 Corynebacterium isolates were submitted for susceptibility testing over the study period. The most commonly identified species was C. striatum (35.6%) followed by C. amycolatum (24.4%). Figure-1 outlines the species distribution. Temporal analysis showed decreasing susceptibility rates over the study period from 47.5% to 20.6% for penicillin & from 50% to 7.6% for clindamycin. Linezolid and vancomycin were universally active against all species (Table-1). Daptomycin non-susceptibility was reported in 25% of C. jeikeium isolates (MIC=2). High level resistance to daptomycin with MIC >256 were noted in seven C. striatum and single C. amycolatum isolate. Doxycycline has the highest susceptibility rates among the tested oral agents after linezolid for the non-striatum species. Significant variation in species-specific susceptibility pattern was noted and summarized in Table 1. C. striatum was associated with concerning resistance rates to beta-lactams, tetracyclines, trimethoprim-sulfamethoxazole & fluoroquinolones with limited reliable oral treatment options beside linezolid. C. kroppenstedtii (associated with granulomatous mastitis) showed high susceptibility rate to tetracyclines and trimethoprim-sulfamethoxazole despite prevalent penicillin resistance. Conclusion Non-diphtheriae Corynebacterium spp are commonly isolated from clinical specimens and are associated with various clinical syndromes. Significant variation in resistance profile exists between different species. Prevalent resistance among the most common species such as C. Striatum is associated with therapeutic challenges. Disclosures Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria Audrey N. Schuetz, MD, Merck: Advisor/Consultant

Abstract Background Vaccine preventable infections (VPIs) are a significant cause of hospitalizations and morbidity and mortality for pediatric solid organ transplant (SOT) recipients. In this single-center study, we assessed up-to-date (UTD) status of routine childhood immunizations among our institution’s pediatric SOT recipients. Methods We collected immunization data on all pediatric patients who underwent liver, kidney, or heart transplants between January 1, 2011 and December 31, 2021 at Mayo Clinic, Rochester, MN by retrospectively reviewing electronic medical record data. We also assessed whether patients were evaluated by a pediatric infectious diseases (PID) specialist within 1 year of transplant. Immunization status was determined using the CDC child and adolescent immunization schedule, excluding seasonal influenza and SARS-CoV-2 immunizations. Results A total of 143 patients were included in our study (n = 45 liver, 54 kidney, 44 heart recipients); 49.7% were male. At the time of transplant, 39 patients were considered UTD (27.3% [Figure 1]). There was no difference by organ type (p = 0.59) and whether patients had seen PID prior to transplant (p = 0.17). Excluding live viral vaccinations, 45 patients were UTD (31.5%). Human papillomavirus was the least UTD vaccine series (Figure 2). Most patients were not UTD in just one or two series (Figure 1). A significant difference in UTD status was found based on age at transplant (p = 0.03), with younger patients having higher rates of UTD status (mean age 7.1 [SD 5.75] vs 9.9 [SD 5.92] years).Figure 1.Vaccination status of pediatric SOT recipients at time of transplant and number of incomplete series.Figure 2.Vaccination status by series for eligible pediatric SOT recipients. Conclusion To date, this study is the largest cohort of pediatric SOT recipients of three organ types assessing routine childhood vaccination status. In this single-center cohort spanning 11 years, we found that less than a third of patients were UTD on routine childhood immunizations at the time of transplant. While some immunizations can be given post-transplant, every effort should be made to update vaccines among transplant candidates to optimize efficacy and protection, thereby reducing the consequences of VPIs within this vulnerable population. Further studies are needed to address reasons for under-immunization and develop strategies to improve vaccination rates. Disclosures All Authors: No reported disclosures

Abstract Background Current approaches to diagnosing suspected native vertebral osteomyelitis (NVO) rely on imaging and microbiological workup, including blood and CT-guided biopsy cultures. These existing diagnostic methods often result in ambiguity, necessitating additional tests to distinguish NVO from its mimics. Our study aims to validate pilot findings demonstrating that an elevated neutrophil differential (PMN) in vertebral bone biopsy/ disc space fluid aspirate is associated with NVO. This may allow stratification of patients with suspected NVO into those who can be monitored closely versus those who may benefit from further invasive testing or empiric antibiotic therapy (Fig 1). Figure 1: Proposed workup of patients with suspected native vertebral osteomyelitis guided by disc space/ vertebral body neutrophil (PMN) differential. Methods This analysis examines a subset of patients from a prospective cohort study, enrolling adults referred to Mayo Clinic's neuroradiology department for spine biopsy. After collecting routine clinical specimens, the needle is rinsed with saline into an EDTA tube for automated cell count and differential analysis. To evaluate the predictive capacity of neutrophil (PMN) differential for NVO, logistic regression models were employed, and receiver operating characteristic (ROC) curve analyses were conducted for various PMN percentage cutoff points. Results In this preliminary analysis, 39 patients were included, comprising 7 patients with NVO and 32 patients with alternative diagnoses. Baseline characteristics are presented in Table 1. All NVO patients received antibiotics within two weeks of the spine biopsy. The median biopsy sample PMN percentage for NVO patients was 83.0 (77.5-88.0), compared to 65.0 (56.5-69.5) for those without NVO (p=0.005) (Fig 2A). The estimated relationship between the probability of NVO and each measure across the full range of percentages is illustrated in Fig 2B. The optimal ROC curve point corresponds to a PMN differential of 72.5% (sensitivity=0.86, specificity=0.81) (Fig 3).Table 1:Baseline Characteristics of Patients Included in the Preliminary AnalysisFigure 2:A) Distribution of spine biopsy neutrophil percent by native vertebral osteomyelitis (NVO) status, B) Loess nonparametric smoother showing the relationship between the probability of NVO and biopsy sample neutrophil percentage.Figure 3:ROC curve analysis of neutrophil percent and NVO Conclusion This preliminary analysis indicates that an elevated PMN differential in spine biopsy samples may serve as a valuable diagnostic tool for NVO, with results seemingly unaffected by recent antibiotic intake. The PMN differential cutoff of 72.5% exhibited notable sensitivity and specificity. Investigations are ongoing to further validate these findings Disclosures Brett Freedman, MD, Clear Choice Therapeutics: Stocks/Bonds|Medtronic: Grant/Research Support|Neuroinnovations: Stocks/Bonds Aaron J. Tande, M.D., Musculoskeletal Infection Society: Board Member|Wolters Kluwer Health - Lippincott Williams & Wilkins: Publishing royalties, financial or material support

Abstract Background Urinary tract infections (UTIs) caused by multidrug-resistant Gram-negative bacilli (MDR-GNB) have become increasingly challenging to manage due to the limited number of available effective oral agents. Minocycline, a second-generation tetracycline with a broad antimicrobial spectrum and reasonable urinary concentration, has recently gained attention as a potential treatment option for MDR-GNB UTIs. In this study, we aim to review the in vitro minocycline susceptibility against a wide spectrum of urinary GNB isolates performed at our reference lab. Methods We conducted a retrospective review of all minocycline susceptibility testing performed on urinary GNB isolates performed at the Mayo Clinic reference lab between 2013-2022. We stratified our results for different species based on phenotypic resistance profiles as well as known species-specific resistance association. Results During the study timeframe, we identified 28,388 GNB isolates that underwent minocycline susceptibility testing. Among the Escherichia coli (E.Coli) isolates resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibility was noted to be 78%, 46%, 76%, respectively (Fig 1). Among the Klebsiella pneumonia (KP) isolate resistant to ceftriaxone, ciprofloxacin, or meropenem, minocycline susceptibilities were 47%, 40%, and 53% respectively (Fig 1). Among the high risk Amp-C group Citrobacter freundii, Enterobacter Cloacae and Klebsiella aerogenes, minocycline susceptibility rate was noted to be 87%, 77%, and 89%, respectively (Fig 2). Finally, among the isolate group of non-fermenters including Achromobacter spp, Acinetobacter spp & Stenotrophomonas spp, susceptibility rates were noted to be 65%, 94%, and 100%, respectively (Fig 3). Conclusion Minocycline showed in vitro activity against many hard to treat GNB urinary isolates, including ceftriaxone and meropenem resistant E.coli & KP isolates. High-risk Amp-C producing GN species & some of the less common GN including Stenotrophomonas, Acinetobacter, and Achromobacter. Disclosures All Authors: No reported disclosures