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Abstract Background Nontuberculous mycobacterial pulmonary disease (NTMPD) is a chronic lung infection that is challenging to treat, especially refractory NTMPD. Data are limited on the natural history, risk profile, and burden of refractory NTMPD. The objective of this study was to evaluate the burden of illness (BOI) among patients with NTMPD who later develop refractory NTMPD vs those who do not. Methods This was a retrospective analysis using BRR data. Patients treated for NTMPD were included and stratified as refractory (received oral clofazimine/bedaquiline or inhaled amikacin/ALIS, or remained sputum culture positive despite ≥ 6 months of treatment) or nonrefractory. Modified bronchiectasis severity index (mBSI) at baseline visit and BOI including comorbid conditions and surgeries at the treatment visit were compared by cross-sectional analysis between the two groups. Longitudinal analysis of BOI focused on exacerbations and hospitalizations in the refractory group at their pre-refractory visit and refractory visit (first visit meeting the refractory definition). Results A total of 1,064 patients treated for NTMPD were included: 462 (43.4%) refractory and 602 (56.6%) nonrefractory. During the baseline period, the refractory group had more severe bronchiectasis (Table 1, mBSI, mean [SD], 7.3 [3.4] vs 6.7 [3.4]). At the time of treatment, bronchiectasis was more common in the refractory than nonrefractory (96.2% vs 89.7%) group, as were hemoptysis (26.6% vs 16.3%) and GERD (50.5% vs 39.9%). Except BMI, there were no statistically significant differences between the pre-refractory and nonrefractory treatment visits (Table 2). In the refractory group, exacerbations and hospitalizations remained high from the pre-refractory to refractory visit (45.6% vs 39.4% and 13.3% vs 12.8%, respectively). Oxygen and bronchial hygiene use increased from the pre-refractory to the refractory visit (5.2% vs 9.3% and 54.5% vs 61.7%, respectively) consistent with increased management of respiratory conditions when not responding to treatment (Table 2). Conclusion Refractory NTMPD imposes a high disease burden on patients in the BRR. This high burden was present at pre-refractory visits and through the development of refractory status. Disclosures Timothy R. Aksamit, MD, AstraZeneca: Advisor/Consultant|Baxter International, Hill-Rom: Advisor/Consultant|Insmed Incorporated: Advisor/Consultant|Johnson & Johnson: Advisor/Consultant|Redhill Biopharma: Advisor/Consultant|RespirTech: Advisor/Consultant|Spero Therapeutics: Advisor/Consultant|Zambon: Advisor/Consultant David M. Mannino, MD, AstraZeneca: Advisor/Consultant|GlaxoSmithKline: Advisor/Consultant|Up to Date: Advisor/Consultant Ping Wang, PhD, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds Mariam Hassan, PhD, B. Pharm, Insmed Incorporated: Salary|Insmed Incorporated: Stocks/Bonds

Abstract Background Febrile neutropenia (FN) is associated with a high risk for infections in patients receiving chemotherapy. Mortality estimates in pediatric patients with FN range from 0.4-3%. Extended infusion (EI) of beta-lactam antibiotics leads to improved pharmacodynamic parameters and is associated with enhanced antimicrobial activity. A recent study demonstrated significantly better overall treatment response in adult patients with documented infections and high-risk FN who received EI vs. standard infusion (SI) piperacillin-tazobactam. There are currently no studies evaluating clinical outcomes of EI beta-lactam use in pediatric patients with FN. Methods This study was a single-center retrospective cohort study with a time frame between September 2016-September 2022. The primary objective was to assess the time to fever resolution in patients with FN who received EI vs. SI of beta-lactam antibiotics. Secondary objectives included the difference in 30-day mortality and hospital length of stay (LOS) between the EI and SI groups. This study included patients admitted to pediatric hematology, oncology, or BMT services at Michigan Medicine who were (1) diagnosed with FN during hospital admission or admitted for FN following chemotherapy and (2) treated with EI or SI cefepime, piperacillin-tazobactam, or meropenem for at least 48 hours. Results A total of 87 patients were included in the study analysis (40 in the EI group and 47 in the SI group). Baseline characteristics were similar between the groups. There was no significant difference in the time to fever resolution for the cohort (48.5 vs 39.1 hours, p=0.373). There were numeric non-significant differences favoring EI for 30-day mortality (0% vs. 4%, p=0.496), and avoiding need to escalate antibiotic therapy due to treatment failure (7.5% vs. 17%, p=0.214). Conclusion The small sample size limited the ability to detect differences in time to fever resolution between EI and SI beta-lactams. Although not statistically significant, secondary endpoints showed numerically lower mortality and lower rates of therapy escalation in the EI group. Disclosures Madeleine King, PharmD, BCOP, Elsevier, Inc: Board Member

Abstract Background Native joint septic arthritis (NJSA) of the wrist is a rare condition, with published literature suggesting an incidence of approximately 1.5% among patients presenting with acute painful and swollen wrist. The aim of this study was to investigate the characteristics, management, and outcomes of wrist NJSA at our institution. Methods We conducted a retrospective study of all adults diagnosed with wrist NJSA who underwent surgical intervention at Mayo Clinic facilities from January 2012 to December 2021. The diagnosis was confirmed based on clinical presentation, synovial fluid white blood cell count, and aspiration or operative cultures. Results A total of 557 patients developed NJSA during the study period, of whom 55 (9.9%) were diagnosed with wrist NJSA, median age was 63, with the associated demographics (Table 1). 12 (21.8%) had a history of antecedent trauma or procedure, 11 (20%) had synchronous joint infections, and 22 (40%) had positive blood cultures. The median synovial white blood cell count was 94,050/mm3 (IQR 51,920 – 139,941 /mm3). Crystals were detected in 5 patients (8.8%). Additional diagnostic data are available in Table 2. Open debridement was performed in 35 (61.4%) patients, and the rest underwent arthroscopy. Positive Gram stain results were detected in the preoperative synovial fluid of 12 (21.8%) cases. The most common pathogen isolated was Staphylococcus aureus in 13 (24%) of cases. The median duration of antimicrobial therapy was 31 days (IQR 26 – 45 days). There was no statistically significant difference in the incidence of complications between patients who underwent open debridement and those who underwent arthroscopy (Table 3). The most common complication of both groups was compromised range of motion of the wrist joint. Conclusion Native wrist septic arthritis comprised 9.9 % of all NJSA during the study period. Concomitant bacteremia and synchronous joint infections were common, highlighting the importance of obtaining blood cultures and comprehensive joint exam in this setting. Crystals and Gram stains were detected in 10 % and 22% of cases, respectively. These findings should not rule out NJSA. Decreased range of motion was common complication, affecting 21% of all cases. Disclosures 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 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

Abstract Background Patent foramen ovale (PFO) can be identified in about 20-25% of the adult population and may result in variable degrees of left-to-right and right-to-left intracardiac shunting. The association between PFO and pyogenic brain abscess remains poorly understood. The current study aimed to compare the clinical characteristics and outcomes of pyogenic brain abscess in patients with and without PFO. Methods All adults with pyogenic brain abscess seen at Mayo Clinic from 1/1/2009-12/31/2021 who underwent either transesophageal echocardiography (TEE) or transthoracic echocardiography (TTE) with agitated saline shunt (bubble) study were included. Results A total of 222 patients developed pyogenic brain abscess during the study period; 148 (66.7%) patients were excluded due to unknown PFO status. Among 74 remaining patients, PFO was detected in 30 (40.5%) patients; 25 by TEE and 5 by TTE with bubble study (Figure 1). The prevalence of cryptogenic brain abscess (unable to identify the source of abscess) was significantly higher in patients with PFO as compared to those without PFO (53.3% versus 18.2%, p=0.002). Patients with PFO had a larger abscess size (25 mm [IQR 15.8-37.5] versus 15.5 mm [IQR 10.0-28.0], p=0.038). However, multiple abscesses were more common in the group without PFO (43.2% versus 20.0%, p=0.038). Additionally, patients with PFO had less documented bloodstream infection. There were no differences between other clinical characteristics and one-year, all-cause mortality between two groups. Conclusion These findings provide critical insights into the likely association between PFO and cryptogenic brain abscess; additional investigation is warranted. Disclosures Larry M. Baddour, MD, Boston Scientific: Advisor/Consultant|Roivant Sciences: Advisor/Consultant

Abstract Background Clostridioides difficile infection (CDI) is a common and potentially life-threatening infection. Transplant recipients are vulnerable to CDI due to immune suppression and frequent antibiotic exposure. CDI can lead to serious complications in these patients, including allograft failure. In a population of pancreas transplant recipients, we aimed to identify epidemiologic characteristics and risk factors associated with CDI within 90 days of transplant. Methods We performed a retrospective cohort study of adults who underwent pancreas transplantation between January 1, 2010, and December 31, 2020, at three centers in Arizona, Florida, and Minnesota. Patients were excluded if they developed pancreas allograft failure within 48 hours of transplantation. The primary outcome was diagnosis of CDI within 90 days of transplantation and the secondary outcome was pancreas allograft failure. The main analyses were performed by Cox regression. Results A total of 482 patients were included, of which 35 (7.3%) developed CDI within 90 days (Table 1). Within the subset of 35 CDI patients, the median time to CDI was 17.0 (IQR 13.0–28.5) days (Figure 1) with most (83%) diagnosed with non-severe CDI. Most patients with CDI were on current systemic antibiotics (94%), primarily for prophylaxis (73%). CDI treatment was vancomycin for the majority of patients (71%) and metronidazole for the rest (29%). One patient had a fecal transplant for recurrence, and none required surgery. In multivariable cox regression of associations with 90-day CDI, significant associations were anastomotic leak (HR 3.04, 95% CI 1.2-7.4; p=0.015) and simultaneous pancreas-kidney transplantation (HR 8.70, 95% CI 1.15-66.7; p=0.036); age (HR 0.97, 95% CI 0.94-1.01; p=0.110) was not significant. In a secondary analysis, CDI was not associated with pancreas allograft failure (p=0.719).Table 1.Characteristics of 482 patients who underwent pancreas transplantation. Conclusion This study identified preceding anastomotic leak as a risk factor for 90-day CDI after pancreas transplantation, likely due to subsequent intra-abdominal infection and antibiotic use. simultaneous pancreas-kidney transplantation is another risk factor due to additional comorbidity. Transplant providers should be cognizant of the risks of CDI and mitigate these risks as possible. Disclosures All Authors: No reported disclosures

Abstract Background Critically ill patients, particularly those treated with extracorporeal devices or at extremes of weight, experience pharmacokinetic variability which can compromise beta-lactam (BL) antibiotic target attainment and treatment response. Therapeutic drug monitoring (TDM) for BL antibiotics can improve precision pharmacotherapy but has had limited implementation. The objective of this study was to evaluate the frequency of BL target attainment among adult intensive care unit (ICU) patients who underwent TDM. Methods This observational study evaluated adults treated with cefepime, piperacillin/tazobactam or meropenem in ICUs at the Mayo Clinic in Rochester, Minnesota who underwent TDM from June-September 2022. During the study timeframe, multidisciplinary teams were encouraged to perform BL TDM on patients requiring extracorporeal membrane oxygenation, continuous kidney replacement therapy, or at an extreme of body weight (weight < 40 kg or >120 kg or BMI < 18 kg/m2 or > 40 kg/m2). Percentage of patients with initial serum trough concentrations within the therapeutic range was calculated (Table 1). Results During the study timeframe, 59 trough concentrations were performed on critically ill patients, of which 5 were excluded due to uninterpretable results. Of the remaining 54 BL trough concentrations analyzed, 49 (91%) were initial troughs during the antibiotic course, and 5 (9%) were repeat troughs. Thirty-six (73%) of the initial trough concentrations were within the therapeutic range. Among the trough concentrations outside the therapeutic range, 10 (77%) were too high, and 3 (23%) were too low (Table 2). Dose adjustment occurred in 19 (39%) of initial trough evaluations, including 6 which were adjusted despite a level within the therapeutic range. All of the repeat trough concentrations drawn during the same antibiotic course were within the therapeutic range (n = 5/5; 100%). Conclusion One-fourth of initial BL trough concentrations were outside of the therapeutic range. BL levels outside the therapeutic range prompted dose adjustment to improve the potential for effectiveness or limit the potential for toxicity. BL TDM appears to be a promising strategy to enhance precision pharmacotherapy in the critically ill. Disclosures Sara Ausman, PharmD, Gilead: Honoraria Christina G. Rivera (O'Connor), Pharm.D, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Board Member|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria

Abstract Background Achromobacter spp. are important pathogens that are most frequently implicated in opportunistic infections, especially in patients with chronic lung disease, malignancy, and solid organ or hematopoietic stem cell transplantations. They commonly cause pneumonia, bacteremia, and device-associated infections. Intrinsic and acquired resistance mechanisms usually complicate treatment. Further characterization of the changing antibiotic susceptibilities and clinical manifestations of Achromobacter spp. are needed to improve clinical practice. Methods We performed a retrospective review of Achromobacter isolates from 2013 to 2023 in the Mayo Clinic Enterprise with available antimicrobial susceptibility testing (AST) data. Variables included sample source, collection date, and AST by agar dilution with susceptibility defined according to Clinical and Laboratory Standards Institute (CLSI) breakpoints. Samples were categorized into quartiles based on collection date and grouped into source types (respiratory, genitourinary, etc.) and AST. Results A total of 1,506 patients were identified with a total of 1,546 unique Achromobacter spp. isolates from 2013 - 2023. The most common species was A. xylosoxidans, encompassing 40.1% of all isolates (Table 1). Respiratory samples (sputum, bronchoalveolar lavage) were the most common source (57.5%), followed by musculoskeletal and soft tissue (16.4%), genitourinary (12.2%), and oropharyngeal sources (10.3%). AST from 2013 to 2023 showed persistent high levels of resistance to aztreonam and tetracycline, with stable susceptibility to piperacillin-tazobactam, trimethoprim-sulfamethoxazole, and carbapenems (Table 2). Over our 10-year analysis, there was increased resistance to aminoglycosides, fluoroquinolones, ceftazidime, and cefepime.Table 1.Achromobacter Species Identification and Isolate Percentage (%) Stratified by Year Table 1 lists the Achromobacter species identified stratified by the year each sample was collected. Each value represents the number of isolates that were identified as the listed Achromobacter species, with "Achromobacter sp." indicating an isolate without species identification. Percentages of species are listed in parentheses (%). Sample totals are listed in the right column.Table 2.Antibiotic Susceptibility of All Tested Achromobacter Isolates (Percentage of Susceptible Isolates) Table 2 lists antibiotics by class, stratified by year that Achromobacter isolates were tested. Each value is the total number of isolates tested for antimicrobial susceptibility, followed by the percentage of susceptible isolates in parentheses (%). Total isolates tested and overall susceptibility percentage is also listed over the 10-year period. Conclusion Achomobacter continues to be a clinically significant organism with a complex resistance profile. Our dataset shows a significant prevalence of non-respiratory and non-genitourinary samples, in addition to increasing resistance over many antibiotic classes. Our data suggests that piperacillin-tazobactam, imipenem, and minocycline are appropriate empiric regiments for Achromobacter. Disclosures All Authors: No reported disclosures

Abstract Background Hospital-acquired and ventilator-associated pneumonia (HAP/VAP) remain significant causes of morbidity and mortality among patients admitted to a medical facility. Consensus guidelines for the treatment of HAP/VAP recommend patients with certain risk factors be empirically treated with an anti-methicillin resistant Staphylococcus aureus (MRSA) and anti-pseudomonal antibiotic. The most commonly utilized anti-pseudomonal agents at BJC hospitals include cefepime, followed by piperacillin/tazobactam and meropenem. The purpose of this study is to determine if there is a difference in clinical outcomes between cefepime and the other most commonly used anti-pseudomonal antibiotics, piperacillin/tazobactam or meropenem, at these institutions for the treatment of HAP/VAP. Methods This retrospective, multicenter cohort study included adult patients with HAP/VAP who received cefepime, meropenem, or piperacillin/tazobactam. Major exclusion criteria included patients that received antibiotics within 48 hours of hospital admission or less than 48 hours of empiric antibiotics. The primary outcome was in-hospital mortality. Secondary outcomes included change in initial antibiotic, mechanical ventilation-free days, ICU length of stay, hospital length of stay, hospital readmission, and new C. difficile infection. Results Of 1,117 included patients, 1,008 patients received cefepime and 109 received meropenem or piperacillin/tazobactam. Incidence of in-hospital mortality was not observed to be significantly different among empiric Gram-negative regimens (cefepime group 19.4% vs. meropenem or piperacillin/tazobactam 22%, p=0.521. Change in initial antibiotic, ICU length of stay, and hospital length of stay were observed to be significantly higher in the cefepime group. Conclusion We observed no difference in in-hospital mortality between cefepime and piperacillin/tazobactam or meropenem. However, there was a significantly higher incidence of change in initial antibiotic, ICU length of stay, and hospital length of stay observed in the cefepime group, though additional research is needed to corroborate these observations. Disclosures Kevin Betthauser, PharmD, La Jolla Pharmaceutical Company: Advisor/Consultant|La Jolla Pharmaceutical Company: Grant/Research Support Paul Juang, Pharm.D., Merck & Co: Grant/Research Support

Abstract Background Eosinopenia has previously been studied as a predictor of bacteremia and sepsis, and has been identified as a marker of increased mortality in critically ill patients. To date, one study has examined changes in eosinophil count during bacterial infection, noting quicker normalization of eosinophil count versus traditional markers of inflammation, whereas no studies have examined eosinophil count recovery as a predictor of blood stream clearance. Methods We conducted a multicenter, retrospective cohort study of adult patients diagnosed with Staphylococcus aureus bacteremia (SAB) between January 2018 and December 2019 at Mayo Clinic campuses. Patients with eosinopenia on the date of the first positive blood culture were selected for further analysis. Eosinopenia was defined as an eosinophil count < 0.03 x10(9)/L. Eosinophil count recovery was defined as the first subsequent date where an eosinophil count ≥0.03 x10(9)/L was recorded. Clearance of SAB was defined as negative blood cultures at 48 hours on two consecutive days, and the date of clearance was defined as the date of first negative blood culture. Results A total of 213 cases of SAB were identified where an eosinophil count was obtained on date of first positive blood culture. Of these cases, 132 (62.0%) had eosinopenia at time of diagnosis. Data related to count recovery was available for 90 patients, with associated characteristics for this cohort detailed in Table 1. S. aureus isolates were oxacillin susceptible in 91.1% (82/90) of cases. The median time to clearance of bacteremia was 2.7 days (IQR 1.8-4.7 days), and the median time to eosinophil count recovery was 2.0 days (IQR 2.0-3.0 days). Data related to timing of eosinophil count recovery are presented in Table 2. Resolution of eosinopenia occurred within 48 hours of bloodstream clearance in 79/90 (87.8%) of cases and preceded or occurred within 48 hours of blood culture clearance in 88/90 (97.8%) of cases. Conclusion Eosinopenia is a common finding at time of diagnosis of SAB, and recovery of eosinophil count is suggestive of imminent clearance of blood cultures. Disclosures All Authors: No reported disclosures

Abstract Background Periprosthetic joint infection (PJI) is associated with significant morbidity. Management includes surgery and prolonged antibiotic treatment. Few studies have evaluated rates of acquired antimicrobial resistance in bacteria causing PJI. The aim of this study was to describe antimicrobial resistance profiles of bacteria causing PJI and to assess whether there was any apparent association between acquired resistance and clinical outcome. Methods Patients at Mayo Clinic with first episodes of knee or hip PJI whose implants underwent sonication between January 2012 and December 2021 were studied. Sonicate fluid cultures from cement spacers or cultures yielding more than one microorganism were excluded. PJI was defined according to IDSA guidelines. Multidrug resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. Outcomes of PJI recurrence, need for further surgery with negative cultures or cultures yielding a new microorganism and amputation were assessed, within one year. Analysis was performed using SAS software version 9.4 (SAS Inc). Results 256 PJI episodes were evaluated, 55% from knees and 45% from hips. Median patient age was 66 years, 52% were men. Resistance profiles are shown in the table. The most frequent microorganisms isolated were S. epidermidis (n=82) and S. aureus (n=50), of which 68% and 30%, respectively, were methicillin resistant. Streptococci, Enterococci, Enterobacterales, and P. aeruginosa were found in 34,16, 8 and 3 cases; none were multidrug-resistant. No differences in PJI recurrence within one year were found in subjects with methicillin-resistant compared to methicillin-susceptible staphylococci (S. aureus, 50% versus 50%, respectively, p, 0.44; S. epidermidis, none), need for further surgery with negative cultures (S. aureus, 20% versus 80%, p, 0.72; S. epidermidis, 80% versus 20%, p, 0.47) or with cultures yielding a new microorganism (S. aureus, none; S. epidermidis, 67% versus 33%, p, 0.96), or amputation (none in any subject with staphylococcal PJI). Conclusion Acquired antimicrobial resistance in PJI was most common in S. epidermidis with methicillin resistance found in 68% and multidrug resistance in 28%. Disclosures Matthew P Abdel, MD, OsteoRemedies: Royalties|Springer: Publishing royalties|Stryker: Royalties reltated to hip and knee implants 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