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Abstract Background Cardiovascular implantable electronic devices (CIED) infection carries significant morbidity, mortality, and financial burden. Bacteremia in patients with CIED increases risk of CIED infection. While several investigations have examined Staphylococcus aureus bacteremia and risk of CIED infection, data regarding non-S. aureus gram-positive coccal (non-SA GPC) bacteremia in patients with CIED has been both limited and dated. The current study examined the clinical characteristics of patients with CIED who developed non-SA GPC bacteremia and their proclivity of CIED infection. Methods We reviewed all patients with CIED who developed non-SA GPC bacteremia at Mayo Clinic between 2012–2019. Cases with a left ventricular assist device, non-hospitalization, and contaminated blood culture were excluded. The 2019 European Heart Rhythm Association International Consensus Document was used to define CIED infection. Results A total of 160 patients with CIED developed non-SA GPC bacteremia during the period. Ninety (56.2%) patients had CIED infection, with 60 (37.5%) classified as definite and 30 (18.8%) possible. This included 41/64 (64.1%) patients with coagulase-negative Staphylococcus (CoNS), 30/41 (73.2%) patients with Enterococcus, 13/19 (68.4%) patients with viridans group streptococci (VGS), and 6/36 (16.6%) patients with other non-SA GPC. The odds of CIED infection (with 95% CI) for CoNS, Enterococcus, and VGS bacteremia were 8.9 (3.2–24.6), 13.6 (4.5–41.6), and 10.8 (2.9–40.0) -fold higher, respectively, as compared to other non-SA GPC. Among those with infected CIED, 51 (56.7%) patients underwent complete device extraction after a median of 6 (IQR 3.5–10) days. In an unadjusted analysis of patients with CIED infection, the reduction in one-year mortality following device removal was not statistically significant (HR 0.59, 95% CI 0.26–1.33, p=0.198). Conclusion The overall prevalence of CIED infection following non-SA GPC bacteremia was higher than previously reported, particularly that due to CoNS, Enterococcus, and VGS. Further study with a larger cohort is needed to demonstrate the survival benefit from CIED extraction in patients with infected CIED due to non-SA GPC. Disclosures Larry M. Baddour, M.D., Boston Scientific: Advisor/Consultant|Botanix Pharmaceuticals: Advisor/Consultant|Roivant Sciences: Advisor/Consultant|UpToDate, Inc.: Royalty payments - authorship duties Rizwan Sohail, M.D., Aziyo Biologics: Advisor/Consultant|Boston Scientific: Advisor/Consultant|Medtronic: Advisor/Consultant|Philips: Advisor/Consultant|Philips: Honoraria Malini Madhavan, M.B.B.S., Biosense Webster: Advisor/Consultant|Biotronik Inc: Advisor/Consultant|Boston Scientific: Grant/Research Support|Convatec: Advisor/Consultant.

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.

Blood cultures have been the gold standard for identifying pathogens in infective endocarditis (IE). Blood culture-negative endocarditis (BCNE), however, occurs in 40% or more of IE cases with the bulk of them due to recent antibiotic exposure prior to obtaining blood cultures. Increasingly, molecular techniques are being used for pathogen identification in cases of BCNE and more recently has included metagenomic next-generation sequencing (mNGS). We therefore performed a literature search on August 31, 2022, that assessed the mNGS in IE and 13 publications were identified and included in a systematic review. Eight (61.5%) of them focused only on IE with mNGS performed on cardiac valve tissue in four studies, plasma in three studies and cardiac implantable electronic devices (CIED) in one study. Gram-positive cocci, including Staphylococcus aureus (n = 31, 8.9%), coagulase-negative staphylococci (n = 61, 17.6%), streptococci (n = 130, 37.5%), and Enterococcus faecalis (n = 23, 6.6%) were the predominant organisms identified by mNGS. Subsequent investigations are needed to further define the utility of mNGS in BCNE and its impact on patient outcomes. Despite some pitfalls, mNGS seems to be of value in pathogen identification in IE cases, particularly in those with BCNE. This study was registered and on the Open Science Framework platform.

Introduction: During the early phase of the coronavirus disease 2019 (COVID-19), remdesivir was only approved for hospitalized patients. Our institution developed hospital-based, outpatient infusion centers for selected hospitalized patients with COVID-19 who had clinical improvement to allow for early dismissal. The outcomes of patients who transitioned to complete remdesivir in the outpatient setting were examined. Methods: Retrospective study of all hospitalized adult patients with COVID-19 who received at least one dose of remdesivir from 11/6/2020 to 11/5/2021 at one of the Mayo Clinic hospitals. Results: Among 3,029 hospitalized patients who received treatment with remdesivir for COVID-19, the majority (89.5%) completed the recommended the five-day course. Among them, 2,169 (80%) completed treatment during hospitalization, while 542 (20.0%) patients were dismissed to complete remdesivir in outpatient infusion centers. Patients who completed the treatment in the outpatient setting had lower odds of death within 28 days (aOR 0.14, 95% CI 0.06-0.32, p<0.001). However, their rate of subsequent hospital encounters within 30 days was higher (aHR 1.88, 95% CI 1.27-2.79, p=0.002). Among patients treated with remdesivir only in the inpatient setting, the adjusted odds of death within 28 days were significantly higher among those who did not complete the 5-day course of remdesivir (aOR 2.07, 95% CI 1.45-2.95, p<0.001). Conclusions: This study describes the clinical outcomes of a strategy of transitioning remdesivir therapy from inpatient to outpatient among selected patients. Mortality was lower among patients who completed the 5-day course of remdesivir.

Abstract Background Gram-negative bacteremia (GNB) as a manifestation of cardiovascular implantable electronic device (CIED) infection is uncommon. Moreover, echocardiography may be nonspecific in its ability to differentiate whether CIED lead masses are infected. We aimed to determine the rate of CIED infection in the setting of GNB. Methods All patients with CIED who were hospitalized with GNB during 2012–2019 at Mayo Clinic were investigated. The definition of CIED infection was based on criteria recommended by the 2019 European Heart Rhythm Association document. Results A total of 126 patients with CIED developed GNB. None of them had signs of pocket infection. Twenty (15.9%) patients underwent transesophageal echocardiography. Overall, 4 (3%) patients had definite CIED infection. None of them underwent CIED extraction; 3 died within 12 weeks and 1 received long-term antibiotic suppression. Ten (8%) patients had possible CIED infection; despite no CIED extraction, no patient had relapsing GNB. We observed a higher rate of CIED infection in patients with Serratia marcescens bacteremia as compared to that in patients with other GNB. Conclusions The rate of CIED infection following GNB was relatively low. However, accurate classification of CIED infection among patients presenting with GNB remains challenging, in part, due to a case definition of CIED infection that is characterized by a low pretest probability in the setting of GNB. Prospective, multicenter studies are needed to determine accurate identification of CIED infection among GNB, so that only patients with true infection undergo device removal.

AbstractBackgroundThere is insufficient evidence regarding postoperative systemic antibiotic prophylaxis use for more than 24 h following cardiovascular implantable electronic devices (CIED) implantation and its impact on infection prevention. However, this strategy remains a common practice in many institutions.MethodsWe conducted a systematic review and meta‐analysis including studies that compared the outcomes of patients: (1) who received preoperative plus 24 h or more of postoperative antibiotic prophylaxis (intervention group); and (2) who received either preoperative only or preoperative plus less than 24 h of antibiotic prophylaxis (control group). Risk of bias was assessed with ROBINS‐I and ROB‐2 tools. Risk ratio (RR) was pooled using random‐effect meta‐analyses with inverse variance method.ResultsEight studies that included two randomized controlled trials (RCTs) and six cohort studies with a total of 26,187 patients were included in the analysis. Overall, there were no differences in outcomes between the two groups, which included rates of CIED infection (RR 0.77, 95% CI 0.42, 1.42), mortality (RR 1.19, 95% CI 0.69, 2.06), pocket hematoma (RR 1.15, 95% CI 0.44, 3.00) or reintervention (RR 0.87, 95% CI 0.22, 3.46). Of note, the results were primarily impacted by the larger RCT.ConclusionsThere was no benefit of postoperative antibiotic prophylaxis for more than 24 h following CIED implantation in the current systematic review and meta‐analysis. This supports the practice advocated by current guidelines which foster antibiotic stewardship and may result in reductions of adverse drug events, selection for antibiotic resistance, and financial costs of prolonged postoperative antibiotic prophylaxis.

AbstractGraft‐versus‐hostdisease (GVHD) following liver transplantation (LT) is rare but can lead tosignificant mortality. The leading cause of death following GVHD diagnosis isinfectious complications. However, there is a lack of clear descriptions concerning infection and antimicrobial management patterns. Our study aims toprovide the focused details of all infectious complications of acute GVHDfollowing LT. We retrospectively reviewed all adult LT recipients with acute GVHD at Mayo Clinic's Transplant Centers from January 1, 2010, to December 31, 2021. Detailed characteristics of infection in each case were described. Among 4,585 LTs performed during this period, 12 (0.3%) patients developed acuteGVHD. The median time from transplantation to GVHD diagnosis was 49.0 days [IQR 31.5–99.0]. Ten (83.3%) patients developed severe infections leading tomortality. The most common cause of infection was nosocomial bacteremia fromenteric bacteria such as vancomycin‐resistant enterococci and gram‐negative bacilli. Other infections included breakthrough invasive fungal infections,cytomegalovirus (CMV) reactivation, and Clostridioides difficile colitis. Antimicrobial prophylaxis strategies in most cases were based on the degree of neutropenia—these include levofloxacin for bacterial prophylaxis, nebulized pentamidine for Pneumocystis jiroveci pneumonia prophylaxis, posaconazole for invasive fungal prophylaxis, and valganciclovir based on CMVstatus. All GVHD patients with severe infections succumbed to thesecomplications. Ourstudy reiterates that despite prophylaxis, infectious complications in GVHDfollowing LT are common and lead to exceptionally high mortality. Individualizedantimicrobial treatment, prophylaxis and monitoring strategies remain a criticalcomponent of GVHD management. Further study to optimize these practices isrequired. image

Abstract Background Increasing use of deep brain stimulation (DBS) over the past 20 years is paralleled by a rise in DBS infections. There is a paucity of data on the diagnosis, management, and outcomes in such infections. We describe our center’s experience with DBS infections. Methods Adults ( &gt;18 years) diagnosed with DBS associated infection between January 1, 2000 and May 1, 2020 were retrospectively reviewed. Data on patient demographics, clinical presentation, microbiology, and management was collected. Results Seventy cases were identified (table 1). The mean age at diagnosis was 58.9 ± 16.5 years. The bulk were free of comorbidities. Parkinson’s disease and essential tremors were the most common indications for DBS placement. The median time from implantation to infection was 4 months [IQR 1,24]. The neurotransmitter and extension wires were the most frequently infected parts. A microbiological diagnosis was made in 89% of cases, 47% of which were polymicrobial. The most commonly identified organisms were Staphylococcus aureus, Cutibacterium acnes, and coagulase-negative staphylococci. For patients with deep infection, 71% had complete device extraction, 20% partial extraction, and 9% device retention; clinical cure at 3 months occurred in 97%, 64% and 100%, respectively (figure 1). On the other hand, 93% of patients with superficial infection had device retention; cure at 3 months was seen in 64% (figure 2). Suppressive oral antibiotics were rarely used, 45% of patients with partial extraction and 26% with device retention. DBS was reimplanted in 71% of patients after complete extraction and led to reinfection in 30% at 1 year follow up. Median time to reimplantation was 2.7 months. All patients who failed at 3 months in the partial extraction and device retention cohorts subsequently underwent complete device removal leading to clinical cure sustained at 1 year follow up. Conclusion All patients who had complete extraction achieved clinical cure at 3-months follow-up, while high failure rates occurred in those with device retention. Most infections were polymicrobial and predominantly caused by gram-positive pathogens. Thirty percent of patients with re-implantation after complete device extraction developed re-infection within 1 year. Disclosures All Authors: No reported disclosures

Abstract Background Cardiovascular implantable electronic device (CIED) implantation has markedly increased over the past two decades. Staphylococcus aureus bacteremia (SAB) occurs in patients with CIED and determination of device infection among patients without clinical findings of pocket site infection is often difficult. Our study examines the characteristics, management, and outcomes of SAB in patients living with CIED using 2019 international criteria to define CIED infection. Methods We conducted a retrospective study of patients with CIED who were hospitalized at Mayo Clinic, Rochester, with SAB from January 1, 2012 to December 31, 2019. Patients who met CIED infection criteria following SAB based on the 2019 European Heart Rhythm Association International Concensus Document were identified. A time-to-event analysis was used to determine the impact, if any, of complete device extraction on outcomes. Results Overall, 110 patients with CIED developed SAB and 92 (83.6%) of them underwent transesophageal echocardiogram (TEE). Eighty-eight (80%) had CIED infection with 57 (51.8%) and 31 (28.2%) patients meeeting criteria for definite and possible CIED infections, respectively. Forty-three (75.4%) patients with definite CIED infection underwent complete device extraction. For possible and rejected CIED infection, the rates of complete device extraction were 35.5% and 27.3%, respectively (p&lt; .001 for each). The primary endpoint of a composite of one-year mortality and SAB relapse had a rate that was significantly lower in patients with CIED infection who underwent complete device extraction as compared to that of patients who did not undergo device extraction (25.9% vs. 76.5%, p&lt; .001). No significant difference in outcomes was seen in the rejected CIED infection group (33.3% vs. 62.5%, p =.27). Conclusion The rate of CIED infections following SAB was higher than that reported previously. Increased use of TEE and a novel case definition with broader diagnostic criteria were likely operative, in part, in accounting for the the higher rate of CIED infections complicating SAB. Complete device removal is critical in patients with either definite or possible CIED infection as defined by the 2019 consensus document to improve one-year mortality and SAB relapse rates. Disclosures Larry M. Baddour, MD, Boston Scientific (Individual(s) Involved: Self): Consultant; Botanix Pharmaceuticals (Individual(s) Involved: Self): Consultant; Roivant Sciences (Individual(s) Involved: Self): Consultant Muhammad R. Sohail, MD, Medtronic (Consultant)Philips (Consultant)