Khodadadi, Ryan B.

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 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 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 Nocardia primarily infects patients who are immunocompromised or those with chronic lung disease. Although disseminated infection is widely recognized as an important prognostic factor, studies have been mixed on its impact on outcomes of nocardiosis. Methods We performed a retrospective cohort study of adults with culture-confirmed nocardiosis. Advanced infection was defined as disseminated infection, cavitary pulmonary infection, or pleural infection. The primary outcome was 1-year mortality, as analyzed by multivariable Cox regression. Results Of 511 patients with culture growth of Nocardia, 374 (73.2%) who had clinical infection were included. The most common infection sites were pulmonary (82.6%), skin (17.9%), and central nervous system (14.2%). In total, 117 (31.3%) patients had advanced infection, including 74 (19.8%) with disseminated infection, 50 (13.4%) with cavitary infection, and 18 (4.8%) with pleural infection. Fifty-nine (15.8%) patients died within 1 year. In multivariable models, disseminated infection was not associated with mortality (hazard ratio, 1.16; 95% CI, .62–2.16; P = .650) while advanced infection was (hazard ratio, 2.48; 95% CI, 1.37–4.49; P = .003). N. farcinica, higher Charlson Comorbidity Index, and culture-confirmed pleural infection were also associated with mortality. Immunocompromised status and combination therapy were not associated with mortality. Conclusions Advanced infection, rather than dissemination alone, predicted worse 1-year mortality after nocardiosis. N. farcinica was associated with mortality, even after adjusting for extent of infection. While patients who were immunocompromised had high rates of disseminated and advanced infection, immunocompromised status did not predict mortality after adjustment. Future studies should account for high-risk characteristics and specific infection sites rather than dissemination alone.

Abstract Background: A multitude of factors are considered in an infectious diseases (ID) training program’s meticulous selection process of ID fellows but their correlation to pre and in-fellowship academic success as well as post-fellowship academic success and short-term outcomes is poorly understood. Our goal was to investigate factors associated with subsequent academic success in fellowship as well as post-fellowship short-term outcomes. Methods: In 2022, we retrospectively analyzed deidentified academic records from 39 graduates of the Mayo Clinic Rochester ID Fellowship Program (July 1, 2013- June 30, 2022). Data abstracted included demographics, degrees, honor society membership, visa/citizenship status, medical school, residency training program, United States Medical Licensure Exam (USMLE) scores, letters of recommendation, in-training examination (ITE) scores, fellowship track, academic rank, career choice, number of honors, awards, and abstracts/publications prior to fellowship, during training, and within 2 years of graduation. Results: Younger fellows had higher USMLE step 1 scores, pre and in-fellowship scholarly productivity, and higher ITE performance. Female fellows had significantly higher USMLE step 3 scores. Prior research experience translated to greater in-fellowship scholarly productivity. Higher USMLE scores were associated with higher ID ITE performance during multiple years of fellowship, but USMLE step 2 clinical knowledge and 3 scores were associated with higher pre and in-fellowship scholarly productivity and receiving an award during fellowship. USMLE step 1 score did not correlate with fellowship performance beyond year 1 and 2 ITE scores. Conclusions: Multiple aspects of a prospective fellow’s application must be considered as part of a holistic reviewprocess for fellowship selection. USMLE step 2 CK and 3 scores may predict fellowship performance across multiple domains.

AbstractBackgroundSpecific pretransplant infections have been associated with poor posttransplant outcomes. However, the impact of pretransplant Nocardia isolation has not been studied.MethodsWe performed a retrospective study from three centers in Arizona, Florida, and Minnesota of patients with Nocardia infection or colonization who subsequently underwent solid organ or hematopoietic stem cell transplantation from November 2011 through April 2022. Outcomes included posttransplant Nocardia infection and mortality.ResultsNine patients with pretransplant Nocardia were included. Two patients were deemed colonized with Nocardia, and the remaining seven had nocardiosis. These patients underwent bilateral lung (N = 5), heart (N = 1), heart‐kidney (N = 1), liver‐kidney (N = 1), and allogeneic stem cell transplantation (N = 1) at a median of 283 (interquartile range [IQR] 152–283) days after Nocardia isolation. Two (22.2%) patients had disseminated infection, and two were receiving active Nocardia treatment at the time of transplantation. One Nocardia isolate was resistant to trimethoprim‐sulfamethoxazole (TMP‐SMX) and all patients received TMP‐SMX prophylaxis posttransplant, often for extended durations. No patients developed posttransplant nocardiosis during a median follow‐up of 1.96 (IQR 0.90–6.33) years. Two patients died during follow‐up, both without evidence of nocardiosis.ConclusionsThis study did not identify any episodes of posttransplant nocardiosis among nine patients with pretransplant Nocardia isolation. As patients with the most severe infections may have been denied transplantation, further studies with larger sample sizes are needed to better analyze any impact of pretransplant Nocardia on posttransplant outcomes. However, among patients who receive posttransplant TMP‐SMX prophylaxis, these data suggest pretransplant Nocardia isolation may not impart a heightened risk of posttransplant nocardiosis. image

Abstract Background Methicillin-susceptible Staphylococcus aureus (MSSA) bacteremia requires weeks of IV antimicrobial therapy for treatment with antistaphylococcal penicillins (ASP) and first-generation cephalosporins being mainstays of therapy. While effective, use of these agents in the outpatient setting requires frequent dosing along with close toxicity monitoring through the duration of therapy. Ceftriaxone is an appealing alternative given daily dosing and tolerability, but efficacy in this setting remains uncertain. We sought to review outcomes of patients who received ceftriaxone versus an ASP and first-generation cephalosporins for definitive therapy of MSSA bacteremia. Methods Following IRB approval, we reviewed medical records of a retrospective adult cohort diagnosed with MSSA bacteremia treated with ceftriaxone, cefazolin, or an ASP between January 2018 and December 2019 at Mayo Clinic campuses. Treatment was defined as the antibiotic used in the outpatient setting. The primary outcome was 90-day treatment failure, defined as a composite of mortality and microbiologic relapse. Secondary outcomes were 30-day treatment failure and individual components of treatment failure. Multivariable Cox regression analysis was performed to analyze for an association between ceftriaxone use and the primary outcome after adjusting for factors that may also impact outcomes. Kaplan-Meier curves were compared utilizing a log-rank test for survival between groups. Results A total of 223 patients with the accompanying characteristics met study criteria (Table 1). Thirty-seven received ceftriaxone (16.5%) and 186 (83.4%) were treated with cefazolin or an ASP. Ninety and 30-day treatment failure were higher in those treated with ceftriaxone (27%, 8.1%) compared to cefazolin or an ASP (8.6%, 3.8%). Multivariable analysis for risk of 90-day treatment failure revealed a hazard ratio of 2.91 for ceftriaxone (Table 2) and a significant difference in event-free survival for those treated with ceftriaxone compared to cefazolin or an ASP (Figure 1). Conclusion Patients receiving definitive therapy with ceftriaxone for MSSA bacteremia experienced a higher rate of 90 and 30-day treatment failure and a lower rate of event-free survival as compared to those treated with cefazolin or an ASP. Disclosures All Authors: No reported disclosures.

Abstract The diagnosis of Q fever can be challenging and a high index of suspicion is necessary. Within this case series, we highlight the utility of the microbial cell-free DNA next-generation sequencing or Karius Test in the timely diagnosis and management of acute Q fever.

Abstract Antispike monoclonal antibody treatment of 180 B-cell-depleted patients with mild-to-moderate coronavirus disease 2019 (COVID-19) resulted in good outcomes overall, with only 12.2% progressing to severe disease, 9.4% requiring hospitalization, 0.6% requiring mechanical ventilation, no deaths within 30 days, and 1.8% developing persistent COVID-19. Antispike monoclonal antibodies appear effective in this immunocompromised population.

AbstractIntroductionAn algorithmic approach, termed the prolonged clot time profile (PROCT), consisting of initial screening with prothrombin time (PT) and activated partial thromboplastin time (aPTT), reflexive mixing studies if indicated, and follow‐up assays depending on initial testing results, offers an efficient approach to delineate the etiology of a prolonged PT/aPTT. Herein, we present the outcomes of the PROCT in the outpatient setting.MethodsIn this retrospective study, we reviewed medical records of consecutive outpatients who had prolonged PT and/or aPTT noted in the routine coagulation laboratory and who had PROCT ordered in our institutional Special Coagulation Laboratory between 2010 and 2017.ResultsOne hundred and six patients, median age 55 years (IQR 30‐67), met our study criteria. Twenty‐nine patients had normal PT/aPTT, while 77 had persistent abnormalities and underwent reflexive testing. A prolonged PT, aPTT, or PT and aPTT was noted in 27 (35%), 27 (35%), and 23 (30%) respectively. Forty‐nine (64%) had an acquired condition, 17 (22%) had a congenital condition, 7 (9%) had unclear etiology, and 4 (5%) were the result of laboratory artifact. The most common known cause of an isolated prolonged PT in our study was vitamin K deficiency in 8 (10%), the most common cause of an isolated prolonged aPTT was lupus anticoagulant in 4 (5%), and the most common cause of prolonged PT and aPTT was liver disease in 11 (14%).ConclusionProlonged PT/aPTT have a wide range of causes, including artifactual prolongation or abnormalities in secondary hemostasis due to both inherited and acquired conditions.