Antibiotic Treatment Duration for Isolated Methicillin-Susceptible Staphylococcus Aureus Native Tricuspid Valve Endocarditis: A Standardized Multidisciplinary Approach

Antibiotic Treatment Duration for Isolated Methicillin-Susceptible Staphylococcus Aureus Native Tricuspid Valve Endocarditis: A Standardized Multidisciplinary Approach | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Antibiotic Treatment Duration for Isolated Methicillin-Susceptible Staphylococcus Aureus Native Tricuspid Valve Endocarditis: A Standardized Multidisciplinary Approach Sami El-Dalati, Bennett Collis, Evan Hall, Talal Alnabelsi, Chloe Cao, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6498341/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Isolated methicillin susceptible Staphylococcus aureus native tricuspid valve endocarditis (MSSA TVIE) is a serious complication of injection drug use with significant associated morbidity and cost. Guideline recommendations differ with respect to the optimal duration and route of antibiotic administration which can contribute to variations in clinical practice. We report the outcomes of treating MSSA TVIE endocarditis using a multidisciplinary team and cardiovascular infectious diseases consult service. Methods: Patient cases were identified from an institutional multidisciplinary endocarditis team registry in a single-center retrospective study. Demographics, treatment and outcomes data were recorded by study investigators. Results: Between September 7th, 2021, and September 7 th , 2024, 34 consecutive patients with definite isolated MSSA TVIE were identified. Patients were treated with antibiotics for a median duration of 28 days (IQR 11 – 41) of which half were treated with oral antibiotics for a median duration of 14 days. During the follow up period there was one relapsed infection within 30 days and one death contributing to a 2.9% in hospital mortality & 90-day mortality. In the study population there were high rates of active injection drug use (79.4%), prior history of infectious endocarditis (23.5%), patient-directed discharge (35.3%). and 90-day readmissions (35.3%). Conclusion Utilizing a standardized approach to patient care, including a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team, patients with MSSA isolated TVIE without metastatic osteoarticular or spinal infections were successfully treated with antibiotic courses of 28 days or less with low-rates of mortality and relapsed infection at 90-days. Endocarditis Right-sided endocarditis MSSA bacteremia Infections in people who inject drugs Multidisciplinary teams Figures Figure 1 Introduction Isolated native tricuspid valve infective endocarditis (TVIE) account for 5–10% of all cases of infective endocarditis (IE) and is associated with lower mortality than left-sided IE. 1 Up to 90% of patients with TVIE may have a history of injection drug use (IDU) and rates of IDU-related TVIE have increased over the last 15 years, correlating with the ongoing opioid epidemic. 2 – 3 Staphylococcus aureus is the causative pathogen in 60–90% of all TVIE and the proportion of cases caused by methicillin-susceptible Staphylococcus aureus (MSSA) varies regionally. 4 Treatment of MSSA TVIE involves antibiotic therapy and in select cases procedural intervention, ideally guided by a multidisciplinary endocarditis team. 5 , 6 Despite MSSA representing one of the most common causes of TVIE, the optimal duration and route of antibiotic administration has not been definitively established. Both the American Heart Association (AHA) and European Society of Cardiology (ESC) have provided recommendations regarding treatment duration. 5 , 6 The 2015 AHA guideline recommend 6 weeks of intravenous antibiotic therapy for most cases of MSSA TVIE but makes a comment that for patients with uncomplicated MSSA TVIE (individuals with no evidence of renal failure, extrapulmonary metastatic infections, meningitis, aortic, or mitral valve involvement) providers can consider treating for as short a duration as 2 weeks. Notably, this recommendation is also 2 weeks shorter than the 4 weeks of treatment that are recommended by the Infectious Diseases Society of America for complicated S. aureus bacteremia. 7 In contrast, the 2022 AHA scientific statement on endocarditis in people who inject drugs (PWIDS) advocated against the use of abbreviated 2-week regimens. 8 The ESC guideline recommends treatment duration of 4–6 weeks for all cases of MSSA IE, regardless of which valves are involved and does not provide specific guidance about how select between the shorter and longer durations. 5 The ESC guideline also advocates for transition to oral antibiotics after 10 days of intravenous therapy in stable patients. 9 However, the ESC recommendations for oral treatment of MSSA IE include 4-times daily dosing with 1 g of dicloxacillin which poses challenges for patient compliance or the use of rifampin which can have substantial drug-drug interactions, particularly for patients on methadone. 10 These inconsistent recommendations from professional societies can lead to a range of treatment plans in clinical practice. Some patients may be offered 2 weeks of treatment or partial oral therapy after 10 days of intravenous antibiotics and others may be treated with 6 weeks of intravenous therapy. This variability can be particularly impactful for PWIDs, many of whom are deemed not suitable to complete outpatient parenteral antimicrobial therapy (OPAT) and are required to remain in the hospital or some other monitored setting to complete treatment. 11 , 12 Multiple studies have demonstrated that administration of OPAT can substantially reduce costs compared to providing inpatient intravenous antibiotic treatment. 13 , 14 In addition to higher costs, longer duration of therapy or inpatient intravenous antibiotic administration may have impact on patient experience as the rate of self-directed discharge is 4 times higher in cases of IDU-related IE compared to non-IDU related IE. 15 Clearly more data about treatment route and duration for MSSA TVIE is needed to guide providers, reduce costs, and improve patient experience and clinical outcomes. In this single-center, retrospective cohort study, we report the 3-year experience treating MSSA isolated native TVIE using a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team. Methods Team Protocol In September 2021, the University of Kentucky Healthcare created a multidisciplinary endocarditis team (MDET) and cardiovascular infectious diseases consult service (CVIDCS). 16 The composition, structure, and day-to-day activity of the CVIDCS and MDET have previously been described. 17 – 20 All patients admitted to UK with TVIE are seen by the CVIDCS and discussed at the weekly MDET conference. All patients with active substance use disorder or a history of IDU are offered addiction medicine consultation. Decisions regarding antibiotic route and duration, percutaneous mechanical aspiration, and valve surgery are made at the MDET weekly meeting. The authors’ multidisciplinary approach to procedural intervention for native TVIE has been previously outlined. 18 , 19 In 2021, the CVIDCS created, implemented and published a standardized protocol for intravenous antibiotic therapy for IE and for transitioning patients with IE to oral antibiotic therapy. 21 For MSSA IE specifically, all patients are initially treated with intravenous cefazolin or nafcillin. For patients with anaphylactic allergies to either medication allergy and immunology consultation is requested for desensitization given the improved clinical outcomes for MSSA bacteremia when treated with anti-staphylococcal beta-lactams compared to vancomycin. 22 , 23 Patients whose blood cultures are persistently positive for ≥ 72 hours are started on combination therapy with ertapenem for synergistic killing of MSSA. 24 , 25 Dual therapy is continued until 2 consecutive blood cultures are negative for 48–72 hours at which time ertapenem is discontinued. In general, all patients with MSSA isolated native TVIE who meet the AHA criteria for uncomplicated disease are treated with 4 weeks of antibiotic therapy. Individuals who leave the hospital via patient directed discharge are typically provided with 2 additional weeks of oral antibiotic therapy and a follow-up appointment in infectious diseases clinic within that time frame. Patient Identification Beginning in September 2021, a registry was created in the hospital’s electronic medical record containing all patients presented at the weekly MDET conference. Institutional review board approval was obtained from the University of Kentucky to establish a database to retrospectively collect each patient’s demographic, comorbidities, diagnostics, treatments, and outcomes data. Patient consent was not required. For patients who did not follow-up in clinic, data for mortality and re-infections were collected based on emergency department visits and admissions to either the authors’ institution or other hospitals in the region. Patients were included in this study if they met modified Duke Criteria for definite MSSA native tricuspid valve endocarditis. 26 Patients were excluded if they had evidence of left-sided IE, any prosthetic valve, a cardiac implantable electronic device (CIED), or left ventricular assist device (LVAD). The primary outcomes included in-hospital and 90-day mortality as well as rates of relapsed infection at 90-days. Secondary outcomes included 30 and 90-day readmission rates. The reporting of this study conformed to the Strengthening the Reporting of Observational Studies in Epidemiology statement. 27 Definition of Terms Active injection drug use was defined as injection substance use within 30-days of the index hospitalization. Persistent bacteremia was defined as blood cultures that were positive for ≥ 72 hours from the initial positive culture. Blood culture clearance was defined by the presence of two consecutive negative blood cultures obtained on separate calendar days. The start date for treatment duration was defined from the date of blood culture clearance. Relapsed infection was defined by the presence of a new positive blood cultures with MSSA after previously documenting negative cultures. Duration of oral antibiotic treatment was confirmed with patients at follow-up. For those who did not follow-up, duration was assumed, based on the number of days they received in the hospital plus the length of the oral antibiotic prescription. Pick-up of the prescription was confirmed with the hospital’s pharmacy. Consolidation antibiotic therapy was defined as oral antibiotic therapy provided for patients with MSSA osteomyelitis with the aim or preventing relapsed infection. Acute renal failure was defined as patients who were initiated on renal replacement therapy during the index hospitalization. Results Study Population Between September 7th, 2021, and September 7th, 2024, 34 patients with definite MSSA isolated native TVIE were identified (Fig. 1 ). Median patient age was 35.5 years (IQR: 29.3–40.8), 52.9% (n = 18) were female, and 88.2% (n = 30) were Caucasian (Table 1 ). Seventy-nine percent (n = 27) had injection drug use and 8 (23.5%) had previous IE. Six patients (17.6%) were transferred from other institutions. Two-third of patients had persistent bacteremia ≥ 72 hours with a median Pittsburgh Bacteremia Score of 1 (0–3). Patients were generally critically ill and over half (55.9%; n = 19) were admitted to the intensive care unit for a median stay of 9 days (4.5–13.5). There were also substantial rates of vasopressor requirements (44.1%) and mechanical ventilation (32.4%). Seven patients (20.6%) had concurrent vertebral osteomyelitis, 4 (11.8%) had sacroiliitis, and 3 (8.8%) had spinal epidural abscesses. There were no other documented sites of deep-seated metastatic infection. Table 1 Demographic information of patients with methicillin-susceptible Staphylococcus aureus native tricuspid valve endocarditis managed by a multidisciplinary team. Variable N = 34 Age, Median (IQR) 35.5 (29.3–40.8) Male, % (n) 47.1 (16) Female, % (n) 52.9 (18) Caucasian, % (n) 88.2 (30) African American, % (n) 5.9 (2) Previous Infective Endocarditis, % (n) 23.5 (8) Active Injection Drug Use, % (n) 79.4 (27) Outside Hospital Transfer, % (n) 17.6 (6) Chronic Dialysis, % (n) 0 (0) Diabetes, % (n) 8.8 (3) Dental Disease, % (n) 35.3 (12) Hepatitis C Viremia, % (n) 52.9 (18) Pregnancy, % (n) 0 (0) Persistent Bacteremia, % (n) 67.6 (23) Pittsburgh Bacteremia Score, Median (IQR) 1 (0–3) ICU Stay, % (n) 55.9 (19) Days of ICU Stay, Median (IQR) 9 (4.5–13.5) Acute Renal Replacement, % (n) 11.8 (4) Vasopressor Requirement, % (n) 44.1 (15) Mechanical Ventilation, % (n) 32.4 (11) Acute Heart Failure, % (n) 26.5 (9) Septic Pulmonary Emboli, % (n) 79.4 (27) Sacroiliitis, % (n) 11.8 (4) Vertebral Osteomyelitis, % (n) 20.6 (7) Spinal Epidural Abscess, % (n) 8.8 (3) Percutaneous Mechanical Aspiration, % (n) 2.9 (1) Tricuspid Valve Replacement, % (n) 0 (0) Patient Management All patients were seen by the CVIDC, discussed by the MDET, and initially treated with intravenous antibiotics for a median duration of 25 days (11–41; Table 2 ). Cefazolin was the most commonly used intravenous antibiotic, administered in 27 patients (79.4%). Eight patients (23.5%) received nafcillin and 1 patient was treated with daptomycin. Two patients who were initially treated with nafcillin were changed to cefazolin or daptomycin after blood culture clearance due to adverse drug reactions. Over half (52.9%; n = 18) of patients received combination therapy with ertapenem for a median duration of 4 days (3–5) before blood culture clearance. Only 1 patient received combination therapy with gentamicin. One patient underwent percutaneous mechanical aspiration and no patients received valve surgery during the index hospitalization. Table 2 Antibiotic management for patients with methicillin-susceptible Staphylococcus aureus native tricuspid valve endocarditis managed by a multidisciplinary team. Variable N = 34 Intravenous Antibiotics, % (n) 100 (34) Duration of Intravenous Antibiotics, Median (IQR) 24 (11–41) Intravenous Cefazolin, % (n) 79.4 (27) Intravenous Nafcillin, % (n) 23.5 (8) Intravenous Daptomycin, % (n) 2.9 (1) Combination Antibiotic Therapy 55.8 (19) Duration of Combination Antibiotic Therapy, Median (IQR) 4 (3–5) Ertapenem Co-administration, % (n) 52.9 (18) Gentamicin Co-administration, % (n) 2.9 (1) Oral Antibiotics for Course Completion, % (n) 50.0 (17) Duration of Oral Therapy, % (n) 14 (12.5–14) Linezolid, % (n) 17.6 (6) Cephalexin, % (n) 5.9 (2) Linezolid with Cefadroxil, % (n) 23.5 (8) Linezolid with Rifampin, % (n) 2.9 (1) Total Duration of Antibiotic Therapy (IV and PO), Median (IQR) 28 (11–41) Seventeen patients (50%) were transitioned to oral antibiotics for a median of 14 days (12.5–14) to complete treatment. Twelve of these individuals were switched due to patient directed discharge. Fifteen of these patients (88.2%) received linezolid including 8 who received co-administered cefadroxil and 1 who received co-administrated rifampin. Six patients received linezolid monotherapy and 2 were treated with cephalexin alone. The median total duration of antibiotic therapy (intravenous plus oral) for treatment of the MSSA isolated native TVIE was 28 days (11–41). Six patients (17.6%) received consolidation therapy for a median of 92.5 days (92–93) for co-occurring osteomyelitis. Patient Outcomes Median length of stay was 21.5 days (11–39.3) and there was 1 in-hospital death after 12 days of antibiotic therapy for an in-hospital mortality of 2.9% (Table 3 ). This patient was diagnosed with endocarditis at another institution before a patient directed discharge and then later presented to our institution in multi-organ failure. There were no additional deaths at 90-days. There was 1 relapsed infection at 30-days in a patient who left self-directed after receiving 2 days of intravenous antibiotic, were not able to take the prescribed oral antibiotics and returned to the hospital with recurrent MSSA bacteremia. There were no additional relapsed infections between 30 and 90-days post discharge. Twelve patients (35.3%) left the hospital via patient directed discharge. There were 12 (35.3%) readmissions at 90-days and 11 of these (92.9%) occurred within 30-days of discharge. Five (41.6%) of the 90-day readmissions occurred in patients who left self-directed. Approximately 60% (n = 20) of patients followed-up in infectious diseases clinic. Thirteen patients (38.2%) had no follow-up at the authors’ institution. Table 3 Clinical outcomes for patients with methicillin-susceptible Staphylococcus aureus native tricuspid valve endocarditis managed by a multidisciplinary team. Variable N = 34 Length of Stay, Median (IQR) 21.5 (11–39.3) Patient Directed Discharge, % (n) 35.3 (12) Inpatient Mortality, % (n) 2.9 (1) 90 Day Mortality, % (n) 2.9 (1) 30-Day Relapsed Infections, % (n) 2.9 (1) 30-Day Readmissions, % (n) 32.4 (11) 90-Day Relapsed Infections, % (n) 2.9 (1) 90-Day Readmission, % (n) 35.3 (12) Intravenous versus Oral Antibiotic Treatment Ten individuals (29.4%) received 6 weeks of exclusively intravenous antibiotic therapy (Table 4 ). Nine of these patients had evidence of vertebral osteomyelitis, sacroiliitis, or spinal epidural abscesses. The one patient who did not had underlying cirrhosis. Patients who received 6 weeks of intravenous antibiotics were more likely to be male compared to patients who received < 6 weeks of intravenous treatment (80% vs. 33.3%; p = .01). There were more patient directed discharges among patients who received < 6 weeks of intravenous antibiotics (45.8% vs. 10%; p = .05) and median length of stay was significantly longer among patients who received 6 weeks of intravenous treatment (44 days vs. 12.5 days; p = .001). Otherwise the two groups were similar with respect to demographics and illness acuity. There were no significant differences in in-hospital and 90-day mortality, 90-day relapsed infection or 90-day all-cause readmission between patients who received < 6 weeks of intravenous antibiotics or 6 weeks of intravenous treatment. Table 4 Comparison of patients with methicillin-susceptible Staphylococcus aureus native tricuspid valve endocarditis treated with 6 weeks of intravenous antibiotics and patients treated with < 6 weeks of intravenous antibiotics. Variable 6 Weeks of Intravenous Antibiotics N = 10 Less than 6 Weeks of Intravenous Antibiotics N = 24 P Value Duration of Intravenous Antibiotics, Median (IQR) 41.5 (41–42) 13 (4–24.5) p < 0.0001 Synergism with Ertapenem, % (n) 60.0 (6) 50.0 (12) 0.60 Oral Antibiotic for Course Completion, % (n) 10.0 (1) 66.7 (16) 0.0030 Persistent Bacteremia, % (n) 70.0 (7) 66.7 (16) 0.85 Pittsburgh Bacteremia Score, Median (IQR) 1 (0–2.8) 1.5 (0–3) 0.85 Prior Infective Endocarditis, % (n) 10.0 (1) 29.2 (7) 0.23 Age, Median (IQR) 40 (31.3–45) 35 (29.8–40) 0.28 Male, % (n) 80.0 (8) 33.3 (8) 0.01 Female, % (n) 20.0 (2) 66.7 (16) 0.01 Caucasian, % (n) 90.0 (9) 87.5 (21) 0.84 African American, % (n) 10.0 (1) 4.2 (1) 0.52 Injection Drug Use, % (n) 70.0 (7) 83.3 (20) 0.39 Hepatitis C Viremia, % (n) 50.0 (5) 54.2 (13) 0.83 Dental Disease, % (n) 20.0 (2) 41.7 (10) 0.23 Diabetes, % (n) 20.0 (2) 4.2 (1) 0.15 Acute Heart Failure, % (n) 30.0 (3) 25.0 (6) 0.77 Septic Pulmonary Emboli, % (n) 70.0 (7) 83.3 (20) 0.39 Epidural Abscess, % (n) 10.0 (1) 8.3 (2) 0.88 Vertebral Osteomyelitis, % (n) 40.0 (4) 12.5 (3) 0.08 ICU Stay, % (n) 50.0 (5) 58.3 (14) 0.66 Days of ICU Stay, Median (IQR) 10 (7–14) 8.5 (4.3–12.8) 0.51 Acute Renal Replacement Therapy, % (n) 20.0 (2) 8.3 (2) 0.34 Vasopressor, % (n) 40.0 (4) 45.8 (11) 0.76 Mechanical Ventilation, % (n) 40.0 (4) 29.2 (7) 0.55 Patient Directed Discharge, % (n) 10.0 (1) 45.8 (11) 0.05 Length of Stay, Median (IQR) 44 (31–45.8) 12.5 (9.8–26.3) 0.001 In-hospital Mortality, % (n) 0 (0) 4.2 (1) 0.52 90 Day Mortality, % (n) 0 (0) 4.2 (1) 0.52 30 Day Relapsed Infection, % (n) 0 (0) 4.2 () 0.54 30 Day All-Cause Readmission, % (n) 20.0 (2) 37.5 (9) 0.33 90 Day Relapsed Infection, % (n) 0 (0) 0 (0) 90 Day All-Cause Readmission, % (n) 30.0 (3) 37.5 (9) 0.68 Discussion This single-center retrospective cohort study reports on 34 patients with MSSA isolated native TVIE managed by a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team. While other, older studies, have reported on outcomes for MSSA TVIE, our study is unique in that it incorporates the use of a multidisciplinary team and reports on a standardized approach to choosing treatment route and duration. There are several notable findings from this study. The median total duration of antibiotic therapy for was 28 days which is 2 weeks shorter than the 6-week duration of therapy often recommended for MSSA isolated native TVIE. 5 , 6 In-hospital and 90-day mortality rates were very low despite high rates of ICU admission, mechanical ventilation and vasopressor support. Half of patients were transitioned to oral antibiotics, allowing them to complete therapy outside of the hospital without evidence of inferior clinical outcomes. This is a particularly important finding as the previously published literature on partial oral antibiotic treatment of endocarditis has primarily focused on left-sided disease. 9 , 28 There were very low rates of percutaneous mechanical aspiration and no valve surgeries, consistent with the authors’ previously published approach to management of native TVIE. 18 , 19 The 28-day median duration of antibiotic therapy is notable since half of patients received < 4 weeks of treatment and one-quarter received 11 days or fewer of antibiotics. This was driven primarily by a high rate of patient directed discharge (35.3%) and all of these occurred in patients with a history of substance use. This occurred even with a dedicated addiction medicine consult service at the study site. While addiction medicine teams have been shown to be effective at initiating medications for opioid use disorder and reducing mortality, at our hospital treatment of symptoms of acute withdrawal are often managed by the primary admitting service. 29 , 30 Published literature suggests that undertreatment of withdrawal and stigma from hospital staff may contribute to patient directed discharge. 31 Other factors affecting discharge may include competing life priorities such as maintaining shelter or caring for children. 31 There were equal numbers of patient directed discharges amongst male and female patients (6 each). Notably more male patients were treated with 6 weeks of intravenous antibiotics but it is difficult to draw definitive conclusions from this finding given the small sample size. Although it is also not possible to conclude in this study exactly what contributed to the high rates of patient directed discharge, it is clear there is substantial room to improve in this area. Six patients left the hospital after receiving 4 or fewer days of intravenous antibiotics. Despite this, 90-day mortality and relapsed infection rates remained low. This was likely driven by the practice of providing prescriptions for 14 days of oral antibiotics for self-directed discharges. Previous data has demonstrated a mortality benefit to providing oral antibiotics at the time of patient directed discharge for patients with S. aureus bacteremia. 32 It appears that a subset of patients can be successfully treated with approximately 2-week courses of antibiotic, as previously demonstrated and recommended by the AHA. 6 , 33 The only relapsed infection in the cohort occurred in a patient who received only 2 days of intravenous antibiotic therapy, left self-directed and did not take the prescribed oral antibiotics. One particular strength of this study is the standardized management approach to patients with isolated native tricuspid valve endocarditis. All patients were seen by infectious diseases providers who primarily specialize in treatment of endovascular infections. The approach to antibiotic therapy was driven by a standardized, written protocol and all patients were initially treated with intravenous anti-staphylococcal beta-lactams and combination antibiotic therapy with ertapenem was utilized in over half of patients. Percutaneous mechanical aspiration was pursued in cases of persistent bacteremia refractory to medical therapy and was required in only 1 patient. Transitions to oral antibiotic therapy were also protocol driven using an internal, evidence-based guideline and primary teams were provided with recommendations for oral antibiotics in the event of patient directed discharge. Follow-up appointments were also made prior to discharge and patients were provided with the contact information for the infectious diseases clinic and CVIDCS nurse navigator. However, as noted above, even with this standardized management approach there were substantial rates of patient directed discharge, readmission and over 40% of patients did not attend any follow-up appointments at the authors’ institution. Limitations Our study is limited by its retrospective, single-center design. Additionally, patients were only included if they were discussed by the multidisciplinary endocarditis team and it’s possible there were other patients with MSSA TVIE admitted to our institution that were excluded. Access to outside hospital records was limited and patients presented to our institution from a wide catchment area. Therefore, it’s possible that other post-discharge complications occurred and were not captured by study investigators. Patients with prosthetic valves, CIEDs and LVADs were excluded and our results cannot be extended to these populations. Conclusion MSSA isolated native TVIE is a potentially life-threatening complication of injection drug use that is associated with significant morbidity and costs. Consensus guidelines do not provide clear recommendations on the ideal antibiotic treatment duration and as a result there can be variability in provider practice. Utilizing a standardized approach to patient care, including a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team, patients with MSSA isolated TVIE without metastatic osteoarticular or spinal infections were successfully treated with antibiotic courses of 28 days or less with low-rates of mortality and relapsed infection at 90-days and notable savings in IV access and hospital days compared to treatment courses of 6 weeks. More research is needed to identify ways to mitigate patient directed discharges and reduce rates of readmission. Declarations Ethics approval and consent to participate : Approved by the University of Kentucky Institutional Review Board (IRB #71514). Patient consent was not required by the IRB. Consent for publication: Patient consent was not required by the IRB. Author contributions: All authors have had access to the manuscript and contributed to its composition. Acknowledgments: Not applicable Funding: There was no funding for this manuscript. Competing interests: The authors have no conflicts of interest to disclose. Availability of data and materials: De-identified data can be made available upon request. References Clarelin A, Rasmussen M, Olaison L et al (2021) Comparing right- and left sided injection-drug related infective endocarditis. Sci Rep 11(1):1177 Moreillon P, Que YA (2004) Infective endocarditis. 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Eur Heart J 44(48):5095–5106 Jakubowski A, Singh-Tan S, Torres-Lockhart K et al (2024) Addiction Consult Service and Inpatient Outcomes Among Patients with OUD. J Gen Intern Med 39(15):2961–2969 Wilson JD, Altieri Dunn SC, Roy P et al (2022) Inpatient Addiction Medicine Consultation Service Impact on Post-discharge Patient Mortality: a Propensity-Matched Analysis. J Gen Intern Med 37(10):2521–2525 Appa A, Adamo M, Le S et al (2022) Patient-Directed Discharges Among Persons Who Use Drugs Hospitalized with Invasive Staphylococcus aureus Infections: Opportunities for Improvement. Am J Med 135(1):91–96 Wildenthal JA, Atkinson A, Lewis S et al (2023) Outcomes of Partial Oral Antibiotic Treatment for Complicated Staphylococcus aureus Bacteremia in People Who Inject Drugs. Clin Infect Dis 76(3):487–496 Fortún J, Navas E, Martínez-Beltrán J et al (2001) Short-course therapy for right-side endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin versus glycopeptides in combination with gentamicin. Clin Infect Dis 33(1):120–125 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6498341","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":454265703,"identity":"56057a70-65a8-4906-8651-c03ffa800352","order_by":0,"name":"Sami El-Dalati","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA9UlEQVRIiWNgGAWjYHACxgM8DBYMDMyMDQc+ALls7EToAWqRYOBhZm58OAOkhZloLQzszcY8IC4hLfINzAcOvKmRkLdnZ2yTtvm1TZ6PmYHxw8cc3FoMDrAlHJxzTMKwhxmoJbfvtmEbMwOz5MxteLQw8Bgc5mGTYIRo6bnNCNTCxsyLR4t8A/+Hwzz/JOzBWix7btsT1ALy+2HeNolEoJZmY4YftxMJajE4zGZwcG6fRHLPYcbGh70Nt5PbgHrx+kW+vfnhgzffbGzb+48/OPDjz23b+e3NBz98xOcwlFhgbAOTDXjUY4A/pCgeBaNgFIyCkQIAxHtNG/1s9gAAAAAASUVORK5CYII=","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Sami","middleName":"","lastName":"El-Dalati","suffix":""},{"id":454265704,"identity":"b456c77b-c657-4946-ae67-40a9d8334018","order_by":1,"name":"Bennett Collis","email":"","orcid":"","institution":"University of Kentucky College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Bennett","middleName":"","lastName":"Collis","suffix":""},{"id":454265705,"identity":"71e3d417-9765-4c74-b25c-729f05bba976","order_by":2,"name":"Evan Hall","email":"","orcid":"","institution":"University of Kentucky College of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Evan","middleName":"","lastName":"Hall","suffix":""},{"id":454265706,"identity":"872ccc96-daa5-4ab9-9622-9a43aadab7cb","order_by":3,"name":"Talal Alnabelsi","email":"","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Talal","middleName":"","lastName":"Alnabelsi","suffix":""},{"id":454265707,"identity":"a0e54d87-8820-4844-895d-33ae07b3752a","order_by":4,"name":"Chloe Cao","email":"","orcid":"","institution":"HCA Healthcare/USF Morsani College of Medicine GME/HCA Florida Trinity","correspondingAuthor":false,"prefix":"","firstName":"Chloe","middleName":"","lastName":"Cao","suffix":""},{"id":454265708,"identity":"4c871f8a-469e-4977-99db-e2a31d8781af","order_by":5,"name":"Meredith Johnson","email":"","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Meredith","middleName":"","lastName":"Johnson","suffix":""},{"id":454265709,"identity":"9f6aafbb-33c3-45c0-8427-1d5e635014a8","order_by":6,"name":"John Gurley","email":"","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"John","middleName":"","lastName":"Gurley","suffix":""},{"id":454265710,"identity":"79d1f4a2-444d-44b6-ad91-5b9b8cc033c9","order_by":7,"name":"Luke Strnad","email":"","orcid":"","institution":"Oregon Health and Science University","correspondingAuthor":false,"prefix":"","firstName":"Luke","middleName":"","lastName":"Strnad","suffix":""},{"id":454265714,"identity":"aa6e3617-5d37-4bf9-904c-d17cb9dddb68","order_by":8,"name":"Hassan Reda","email":"","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Hassan","middleName":"","lastName":"Reda","suffix":""},{"id":454265715,"identity":"544c46a2-f5c4-495b-b0f9-15369181ddc0","order_by":9,"name":"Michael Sekela","email":"","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Michael","middleName":"","lastName":"Sekela","suffix":""},{"id":454265716,"identity":"2609789f-dc58-4d9b-85d5-e28c81f17d47","order_by":10,"name":"Armaghan-E-Rehman Mansoor","email":"","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Armaghan-E-Rehman","middleName":"","lastName":"Mansoor","suffix":""},{"id":454265717,"identity":"d30db96e-778f-4480-b7e5-51b910eddb0c","order_by":11,"name":"David Olafsson","email":"","orcid":"","institution":"University of Kentucky Medical Center","correspondingAuthor":false,"prefix":"","firstName":"David","middleName":"","lastName":"Olafsson","suffix":""},{"id":454265718,"identity":"71984930-1dc3-400e-b00e-816939765cd4","order_by":12,"name":"William Harris","email":"","orcid":"","institution":"University of Kentucky College of Pharmacy Lexington","correspondingAuthor":false,"prefix":"","firstName":"William","middleName":"","lastName":"Harris","suffix":""},{"id":454265719,"identity":"57f0d0f5-c8d0-4af7-a103-4ffd8fd25070","order_by":13,"name":"Bobbi Jo Stoner","email":"","orcid":"","institution":"University of Kentucky College of Pharmacy Lexington","correspondingAuthor":false,"prefix":"","firstName":"Bobbi","middleName":"Jo","lastName":"Stoner","suffix":""}],"badges":[],"createdAt":"2025-04-21 19:23:04","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6498341/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6498341/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82617943,"identity":"77e4fc2f-8392-4197-86a2-2d8f451fd435","added_by":"auto","created_at":"2025-05-13 11:55:18","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":749037,"visible":true,"origin":"","legend":"\u003cp\u003eStudy enrollment flowchart.\u003c/p\u003e\n\u003cp\u003eFigure 1 Alt Text. 521 patients with suspected endocarditis managed by a multidisciplinary team were screened for enrollment. 355 patients without MSSA bacteremia were excluded and leaving 166 patients with MSSA bacteremia who were further analyzed. 132 additional patients were excluded, including 129 patients with left-sided or multi-valve endocarditis and 3 patients with native tricuspid valve endocarditis and CIEDs. 34 patients with MSSA isolated native tricuspid valve endocarditis were then included in the study (Abbreviations: Methicillins-susceptible \u003cem\u003eStaphylococcus aureus \u003c/em\u003e= MSSA; Cardiac implantable electronic device = CIED).\u003c/p\u003e","description":"","filename":"MSSAPaperFigure1300dpi.png","url":"https://assets-eu.researchsquare.com/files/rs-6498341/v1/c3b86ef232f49dde496383ad.png"},{"id":83441004,"identity":"250ea284-8e8e-4fa8-bebd-64a38ab68659","added_by":"auto","created_at":"2025-05-26 09:33:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1409816,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6498341/v1/0f9b7623-959d-411b-8077-0adbc8a154d6.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Antibiotic Treatment Duration for Isolated Methicillin-Susceptible Staphylococcus Aureus Native Tricuspid Valve Endocarditis: A Standardized Multidisciplinary Approach","fulltext":[{"header":"Introduction","content":"\u003cp\u003eIsolated native tricuspid valve infective endocarditis (TVIE) account for 5\u0026ndash;10% of all cases of infective endocarditis (IE) and is associated with lower mortality than left-sided IE.\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e Up to 90% of patients with TVIE may have a history of injection drug use (IDU) and rates of IDU-related TVIE have increased over the last 15 years, correlating with the ongoing opioid epidemic.\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e\u003cem\u003eStaphylococcus aureus\u003c/em\u003e is the causative pathogen in 60\u0026ndash;90% of all TVIE and the proportion of cases caused by methicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (MSSA) varies regionally.\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e Treatment of MSSA TVIE involves antibiotic therapy and in select cases procedural intervention, ideally guided by a multidisciplinary endocarditis team.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e Despite MSSA representing one of the most common causes of TVIE, the optimal duration and route of antibiotic administration has not been definitively established. Both the American Heart Association (AHA) and European Society of Cardiology (ESC) have provided recommendations regarding treatment duration.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e The 2015 AHA guideline recommend 6 weeks of intravenous antibiotic therapy for most cases of MSSA TVIE but makes a comment that for patients with uncomplicated MSSA TVIE (individuals with no evidence of renal failure, extrapulmonary metastatic infections, meningitis, aortic, or mitral valve involvement) providers can consider treating for as short a duration as 2 weeks. Notably, this recommendation is also 2 weeks shorter than the 4 weeks of treatment that are recommended by the Infectious Diseases Society of America for complicated \u003cem\u003eS. aureus\u003c/em\u003e bacteremia.\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e In contrast, the 2022 AHA scientific statement on endocarditis in people who inject drugs (PWIDS) advocated against the use of abbreviated 2-week regimens.\u003csup\u003e\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e The ESC guideline recommends treatment duration of 4\u0026ndash;6 weeks for all cases of MSSA IE, regardless of which valves are involved and does not provide specific guidance about how select between the shorter and longer durations.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e The ESC guideline also advocates for transition to oral antibiotics after 10 days of intravenous therapy in stable patients.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e However, the ESC recommendations for oral treatment of MSSA IE include 4-times daily dosing with 1 g of dicloxacillin which poses challenges for patient compliance or the use of rifampin which can have substantial drug-drug interactions, particularly for patients on methadone.\u003csup\u003e\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThese inconsistent recommendations from professional societies can lead to a range of treatment plans in clinical practice. Some patients may be offered 2 weeks of treatment or partial oral therapy after 10 days of intravenous antibiotics and others may be treated with 6 weeks of intravenous therapy. This variability can be particularly impactful for PWIDs, many of whom are deemed not suitable to complete outpatient parenteral antimicrobial therapy (OPAT) and are required to remain in the hospital or some other monitored setting to complete treatment.\u003csup\u003e\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u003c/sup\u003e Multiple studies have demonstrated that administration of OPAT can substantially reduce costs compared to providing inpatient intravenous antibiotic treatment.\u003csup\u003e\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e,\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e\u003c/sup\u003e In addition to higher costs, longer duration of therapy or inpatient intravenous antibiotic administration may have impact on patient experience as the rate of self-directed discharge is 4 times higher in cases of IDU-related IE compared to non-IDU related IE.\u003csup\u003e\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e Clearly more data about treatment route and duration for MSSA TVIE is needed to guide providers, reduce costs, and improve patient experience and clinical outcomes.\u003c/p\u003e \u003cp\u003eIn this single-center, retrospective cohort study, we report the 3-year experience treating MSSA isolated native TVIE using a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team.\u003c/p\u003e"},{"header":"Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eTeam Protocol\u003c/h2\u003e \u003cp\u003eIn September 2021, the University of Kentucky Healthcare created a multidisciplinary endocarditis team (MDET) and cardiovascular infectious diseases consult service (CVIDCS).\u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e The composition, structure, and day-to-day activity of the CVIDCS and MDET have previously been described.\u003csup\u003e\u003cspan additionalcitationids=\"CR18 CR19\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e All patients admitted to UK with TVIE are seen by the CVIDCS and discussed at the weekly MDET conference. All patients with active substance use disorder or a history of IDU are offered addiction medicine consultation. Decisions regarding antibiotic route and duration, percutaneous mechanical aspiration, and valve surgery are made at the MDET weekly meeting. The authors\u0026rsquo; multidisciplinary approach to procedural intervention for native TVIE has been previously outlined.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e In 2021, the CVIDCS created, implemented and published a standardized protocol for intravenous antibiotic therapy for IE and for transitioning patients with IE to oral antibiotic therapy.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e For MSSA IE specifically, all patients are initially treated with intravenous cefazolin or nafcillin. For patients with anaphylactic allergies to either medication allergy and immunology consultation is requested for desensitization given the improved clinical outcomes for MSSA bacteremia when treated with anti-staphylococcal beta-lactams compared to vancomycin.\u003csup\u003e\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e,\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u003c/sup\u003e Patients whose blood cultures are persistently positive for \u0026ge;\u0026thinsp;72 hours are started on combination therapy with ertapenem for synergistic killing of MSSA.\u003csup\u003e\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e Dual therapy is continued until 2 consecutive blood cultures are negative for 48\u0026ndash;72 hours at which time ertapenem is discontinued. In general, all patients with MSSA isolated native TVIE who meet the AHA criteria for uncomplicated disease are treated with 4 weeks of antibiotic therapy. Individuals who leave the hospital via patient directed discharge are typically provided with 2 additional weeks of oral antibiotic therapy and a follow-up appointment in infectious diseases clinic within that time frame.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient Identification\u003c/h3\u003e\n\u003cp\u003eBeginning in September 2021, a registry was created in the hospital\u0026rsquo;s electronic medical record containing all patients presented at the weekly MDET conference. Institutional review board approval was obtained from the University of Kentucky to establish a database to retrospectively collect each patient\u0026rsquo;s demographic, comorbidities, diagnostics, treatments, and outcomes data. Patient consent was not required. For patients who did not follow-up in clinic, data for mortality and re-infections were collected based on emergency department visits and admissions to either the authors\u0026rsquo; institution or other hospitals in the region.\u003c/p\u003e \u003cp\u003ePatients were included in this study if they met modified Duke Criteria for definite MSSA native tricuspid valve endocarditis.\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e Patients were excluded if they had evidence of left-sided IE, any prosthetic valve, a cardiac implantable electronic device (CIED), or left ventricular assist device (LVAD). The primary outcomes included in-hospital and 90-day mortality as well as rates of relapsed infection at 90-days. Secondary outcomes included 30 and 90-day readmission rates.\u003c/p\u003e \u003cp\u003eThe reporting of this study conformed to the Strengthening the Reporting of Observational Studies in Epidemiology statement.\u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n\u003ch3\u003eDefinition of Terms\u003c/h3\u003e\n\u003cp\u003eActive injection drug use was defined as injection substance use within 30-days of the index hospitalization. Persistent bacteremia was defined as blood cultures that were positive for \u0026ge;\u0026thinsp;72 hours from the initial positive culture. Blood culture clearance was defined by the presence of two consecutive negative blood cultures obtained on separate calendar days. The start date for treatment duration was defined from the date of blood culture clearance. Relapsed infection was defined by the presence of a new positive blood cultures with MSSA after previously documenting negative cultures.\u003c/p\u003e \u003cp\u003eDuration of oral antibiotic treatment was confirmed with patients at follow-up. For those who did not follow-up, duration was assumed, based on the number of days they received in the hospital plus the length of the oral antibiotic prescription. Pick-up of the prescription was confirmed with the hospital\u0026rsquo;s pharmacy.\u003c/p\u003e \u003cp\u003eConsolidation antibiotic therapy was defined as oral antibiotic therapy provided for patients with MSSA osteomyelitis with the aim or preventing relapsed infection.\u003c/p\u003e \u003cp\u003eAcute renal failure was defined as patients who were initiated on renal replacement therapy during the index hospitalization.\u003c/p\u003e"},{"header":"Results","content":"\u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStudy Population\u003c/h2\u003e \u003cp\u003eBetween September 7th, 2021, and September 7th, 2024, 34 patients with definite MSSA isolated native TVIE were identified (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Median patient age was 35.5 years (IQR: 29.3\u0026ndash;40.8), 52.9% (n\u0026thinsp;=\u0026thinsp;18) were female, and 88.2% (n\u0026thinsp;=\u0026thinsp;30) were Caucasian (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Seventy-nine percent (n\u0026thinsp;=\u0026thinsp;27) had injection drug use and 8 (23.5%) had previous IE. Six patients (17.6%) were transferred from other institutions. Two-third of patients had persistent bacteremia\u0026thinsp;\u0026ge;\u0026thinsp;72 hours with a median Pittsburgh Bacteremia Score of 1 (0\u0026ndash;3). Patients were generally critically ill and over half (55.9%; n\u0026thinsp;=\u0026thinsp;19) were admitted to the intensive care unit for a median stay of 9 days (4.5\u0026ndash;13.5). There were also substantial rates of vasopressor requirements (44.1%) and mechanical ventilation (32.4%). Seven patients (20.6%) had concurrent vertebral osteomyelitis, 4 (11.8%) had sacroiliitis, and 3 (8.8%) had spinal epidural abscesses. There were no other documented sites of deep-seated metastatic infection.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDemographic information of patients with methicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e native tricuspid valve endocarditis managed by a multidisciplinary team.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;34\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.5 (29.3\u0026ndash;40.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47.1 (16)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.9 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaucasian, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e88.2 (30)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfrican American, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrevious Infective Endocarditis, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.5 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eActive Injection Drug Use, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.4 (27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutside Hospital Transfer, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.6 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eChronic Dialysis, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.8 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDental Disease, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35.3 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatitis C Viremia, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.9 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePregnancy, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePersistent Bacteremia, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e67.6 (23)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePittsburgh Bacteremia Score, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU Stay, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.9 (19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays of ICU Stay, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (4.5\u0026ndash;13.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute Renal Replacement, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.8 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressor Requirement, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44.1 (15)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical Ventilation, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32.4 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute Heart Failure, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26.5 (9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeptic Pulmonary Emboli, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.4 (27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSacroiliitis, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.8 (4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVertebral Osteomyelitis, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.6 (7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSpinal Epidural Abscess, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8.8 (3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePercutaneous Mechanical Aspiration, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTricuspid Valve Replacement, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003ePatient Management\u003c/h2\u003e \u003cp\u003eAll patients were seen by the CVIDC, discussed by the MDET, and initially treated with intravenous antibiotics for a median duration of 25 days (11\u0026ndash;41; Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Cefazolin was the most commonly used intravenous antibiotic, administered in 27 patients (79.4%). Eight patients (23.5%) received nafcillin and 1 patient was treated with daptomycin. Two patients who were initially treated with nafcillin were changed to cefazolin or daptomycin after blood culture clearance due to adverse drug reactions. Over half (52.9%; n\u0026thinsp;=\u0026thinsp;18) of patients received combination therapy with ertapenem for a median duration of 4 days (3\u0026ndash;5) before blood culture clearance. Only 1 patient received combination therapy with gentamicin. One patient underwent percutaneous mechanical aspiration and no patients received valve surgery during the index hospitalization.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eAntibiotic management for patients with methicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e native tricuspid valve endocarditis managed by a multidisciplinary team.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;34\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous Antibiotics, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e100 (34)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of Intravenous Antibiotics, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (11\u0026ndash;41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous Cefazolin, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e79.4 (27)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous Nafcillin, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.5 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIntravenous Daptomycin, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCombination Antibiotic Therapy\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e55.8 (19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of Combination Antibiotic Therapy, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (3\u0026ndash;5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eErtapenem Co-administration, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.9 (18)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGentamicin Co-administration, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral Antibiotics for Course Completion, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.0 (17)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of Oral Therapy, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (12.5\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLinezolid, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17.6 (6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCephalexin, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5.9 (2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLinezolid with Cefadroxil, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23.5 (8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLinezolid with Rifampin, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal Duration of Antibiotic Therapy (IV and PO), Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28 (11\u0026ndash;41)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eSeventeen patients (50%) were transitioned to oral antibiotics for a median of 14 days (12.5\u0026ndash;14) to complete treatment. Twelve of these individuals were switched due to patient directed discharge. Fifteen of these patients (88.2%) received linezolid including 8 who received co-administered cefadroxil and 1 who received co-administrated rifampin. Six patients received linezolid monotherapy and 2 were treated with cephalexin alone. The median total duration of antibiotic therapy (intravenous plus oral) for treatment of the MSSA isolated native TVIE was 28 days (11\u0026ndash;41). Six patients (17.6%) received consolidation therapy for a median of 92.5 days (92\u0026ndash;93) for co-occurring osteomyelitis.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003ePatient Outcomes\u003c/h3\u003e\n\u003cp\u003eMedian length of stay was 21.5 days (11\u0026ndash;39.3) and there was 1 in-hospital death after 12 days of antibiotic therapy for an in-hospital mortality of 2.9% (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e). This patient was diagnosed with endocarditis at another institution before a patient directed discharge and then later presented to our institution in multi-organ failure. There were no additional deaths at 90-days. There was 1 relapsed infection at 30-days in a patient who left self-directed after receiving 2 days of intravenous antibiotic, were not able to take the prescribed oral antibiotics and returned to the hospital with recurrent MSSA bacteremia. There were no additional relapsed infections between 30 and 90-days post discharge. Twelve patients (35.3%) left the hospital via patient directed discharge. There were 12 (35.3%) readmissions at 90-days and 11 of these (92.9%) occurred within 30-days of discharge. Five (41.6%) of the 90-day readmissions occurred in patients who left self-directed. Approximately 60% (n\u0026thinsp;=\u0026thinsp;20) of patients followed-up in infectious diseases clinic. Thirteen patients (38.2%) had no follow-up at the authors\u0026rsquo; institution.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical outcomes for patients with methicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e native tricuspid valve endocarditis managed by a multidisciplinary team.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;34\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of Stay, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e21.5 (11\u0026ndash;39.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient Directed Discharge, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35.3 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInpatient Mortality, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90 Day Mortality, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-Day Relapsed Infections, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-Day Readmissions, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32.4 (11)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90-Day Relapsed Infections, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e2.9 (1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90-Day Readmission, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35.3 (12)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e\n\u003ch3\u003eIntravenous versus Oral Antibiotic Treatment\u003c/h3\u003e\n\u003cp\u003eTen individuals (29.4%) received 6 weeks of exclusively intravenous antibiotic therapy (Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). Nine of these patients had evidence of vertebral osteomyelitis, sacroiliitis, or spinal epidural abscesses. The one patient who did not had underlying cirrhosis. Patients who received 6 weeks of intravenous antibiotics were more likely to be male compared to patients who received\u0026thinsp;\u0026lt;\u0026thinsp;6 weeks of intravenous treatment (80% vs. 33.3%; p\u0026thinsp;=\u0026thinsp;.01). There were more patient directed discharges among patients who received\u0026thinsp;\u0026lt;\u0026thinsp;6 weeks of intravenous antibiotics (45.8% vs. 10%; p\u0026thinsp;=\u0026thinsp;.05) and median length of stay was significantly longer among patients who received 6 weeks of intravenous treatment (44 days vs. 12.5 days; p\u0026thinsp;=\u0026thinsp;.001). Otherwise the two groups were similar with respect to demographics and illness acuity. There were no significant differences in in-hospital and 90-day mortality, 90-day relapsed infection or 90-day all-cause readmission between patients who received\u0026thinsp;\u0026lt;\u0026thinsp;6 weeks of intravenous antibiotics or 6 weeks of intravenous treatment.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eComparison of patients with methicillin-susceptible \u003cem\u003eStaphylococcus aureus\u003c/em\u003e native tricuspid valve endocarditis treated with 6 weeks of intravenous antibiotics and patients treated with \u0026lt;\u0026thinsp;6 weeks of intravenous antibiotics.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariable\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6 Weeks of Intravenous Antibiotics\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;10\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLess than 6 Weeks of Intravenous Antibiotics\u003c/p\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;24\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eP Value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDuration of Intravenous Antibiotics, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e41.5 (41\u0026ndash;42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (4\u0026ndash;24.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ep\u0026thinsp;\u0026lt;\u0026thinsp;0.0001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSynergism with Ertapenem, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50.0 (12)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.60\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOral Antibiotic for Course Completion, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.7 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.0030\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePersistent Bacteremia, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.0 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.7 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePittsburgh Bacteremia Score, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (0\u0026ndash;2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.5 (0\u0026ndash;3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.85\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrior Infective Endocarditis, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.2 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40 (31.3\u0026ndash;45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (29.8\u0026ndash;40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.28\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e80.0 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e33.3 (8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e66.7 (16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCaucasian, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e90.0 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e87.5 (21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.84\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAfrican American, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInjection Drug Use, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.0 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.3 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHepatitis C Viremia, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.0 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.2 (13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDental Disease, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e41.7 (10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.23\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDiabetes, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.15\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute Heart Failure, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e25.0 (6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.77\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSeptic Pulmonary Emboli, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.0 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e83.3 (20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.39\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEpidural Abscess, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.88\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVertebral Osteomyelitis, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.08\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eICU Stay, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50.0 (5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58.3 (14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.66\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDays of ICU Stay, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (7\u0026ndash;14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.5 (4.3\u0026ndash;12.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.51\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAcute Renal Replacement Therapy, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.3 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.34\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVasopressor, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.8 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.76\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical Ventilation, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e40.0 (4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29.2 (7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePatient Directed Discharge, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10.0 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e45.8 (11)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLength of Stay, Median (IQR)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e44 (31\u0026ndash;45.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.5 (9.8\u0026ndash;26.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIn-hospital Mortality, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90 Day Mortality, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2 (1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.52\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30 Day Relapsed Infection, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.2 ()\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.54\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30 Day All-Cause Readmission, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20.0 (2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.5 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90 Day Relapsed Infection, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e90 Day All-Cause Readmission, % (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30.0 (3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e37.5 (9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.68\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThis single-center retrospective cohort study reports on 34 patients with MSSA isolated native TVIE managed by a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team. While other, older studies, have reported on outcomes for MSSA TVIE, our study is unique in that it incorporates the use of a multidisciplinary team and reports on a standardized approach to choosing treatment route and duration. There are several notable findings from this study. The median total duration of antibiotic therapy for was 28 days which is 2 weeks shorter than the 6-week duration of therapy often recommended for MSSA isolated native TVIE.\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e,\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e In-hospital and 90-day mortality rates were very low despite high rates of ICU admission, mechanical ventilation and vasopressor support. Half of patients were transitioned to oral antibiotics, allowing them to complete therapy outside of the hospital without evidence of inferior clinical outcomes. This is a particularly important finding as the previously published literature on partial oral antibiotic treatment of endocarditis has primarily focused on left-sided disease.\u003csup\u003e\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e There were very low rates of percutaneous mechanical aspiration and no valve surgeries, consistent with the authors\u0026rsquo; previously published approach to management of native TVIE.\u003csup\u003e\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e,\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eThe 28-day median duration of antibiotic therapy is notable since half of patients received\u0026thinsp;\u0026lt;\u0026thinsp;4 weeks of treatment and one-quarter received 11 days or fewer of antibiotics. This was driven primarily by a high rate of patient directed discharge (35.3%) and all of these occurred in patients with a history of substance use. This occurred even with a dedicated addiction medicine consult service at the study site. While addiction medicine teams have been shown to be effective at initiating medications for opioid use disorder and reducing mortality, at our hospital treatment of symptoms of acute withdrawal are often managed by the primary admitting service.\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e Published literature suggests that undertreatment of withdrawal and stigma from hospital staff may contribute to patient directed discharge.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e Other factors affecting discharge may include competing life priorities such as maintaining shelter or caring for children.\u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e There were equal numbers of patient directed discharges amongst male and female patients (6 each). Notably more male patients were treated with 6 weeks of intravenous antibiotics but it is difficult to draw definitive conclusions from this finding given the small sample size. Although it is also not possible to conclude in this study exactly what contributed to the high rates of patient directed discharge, it is clear there is substantial room to improve in this area.\u003c/p\u003e \u003cp\u003eSix patients left the hospital after receiving 4 or fewer days of intravenous antibiotics. Despite this, 90-day mortality and relapsed infection rates remained low. This was likely driven by the practice of providing prescriptions for 14 days of oral antibiotics for self-directed discharges. Previous data has demonstrated a mortality benefit to providing oral antibiotics at the time of patient directed discharge for patients with \u003cem\u003eS. aureus\u003c/em\u003e bacteremia.\u003csup\u003e\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u003c/sup\u003e It appears that a subset of patients can be successfully treated with approximately 2-week courses of antibiotic, as previously demonstrated and recommended by the AHA.\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e,\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u003c/sup\u003e The only relapsed infection in the cohort occurred in a patient who received only 2 days of intravenous antibiotic therapy, left self-directed and did not take the prescribed oral antibiotics.\u003c/p\u003e \u003cp\u003eOne particular strength of this study is the standardized management approach to patients with isolated native tricuspid valve endocarditis. All patients were seen by infectious diseases providers who primarily specialize in treatment of endovascular infections. The approach to antibiotic therapy was driven by a standardized, written protocol and all patients were initially treated with intravenous anti-staphylococcal beta-lactams and combination antibiotic therapy with ertapenem was utilized in over half of patients. Percutaneous mechanical aspiration was pursued in cases of persistent bacteremia refractory to medical therapy and was required in only 1 patient. Transitions to oral antibiotic therapy were also protocol driven using an internal, evidence-based guideline and primary teams were provided with recommendations for oral antibiotics in the event of patient directed discharge. Follow-up appointments were also made prior to discharge and patients were provided with the contact information for the infectious diseases clinic and CVIDCS nurse navigator. However, as noted above, even with this standardized management approach there were substantial rates of patient directed discharge, readmission and over 40% of patients did not attend any follow-up appointments at the authors\u0026rsquo; institution.\u003c/p\u003e \u003cdiv id=\"Sec12\" class=\"Section2\"\u003e \u003ch2\u003eLimitations\u003c/h2\u003e \u003cp\u003eOur study is limited by its retrospective, single-center design. Additionally, patients were only included if they were discussed by the multidisciplinary endocarditis team and it\u0026rsquo;s possible there were other patients with MSSA TVIE admitted to our institution that were excluded. Access to outside hospital records was limited and patients presented to our institution from a wide catchment area. Therefore, it\u0026rsquo;s possible that other post-discharge complications occurred and were not captured by study investigators. Patients with prosthetic valves, CIEDs and LVADs were excluded and our results cannot be extended to these populations.\u003c/p\u003e \u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003eMSSA isolated native TVIE is a potentially life-threatening complication of injection drug use that is associated with significant morbidity and costs. Consensus guidelines do not provide clear recommendations on the ideal antibiotic treatment duration and as a result there can be variability in provider practice. Utilizing a standardized approach to patient care, including a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team, patients with MSSA isolated TVIE without metastatic osteoarticular or spinal infections were successfully treated with antibiotic courses of 28 days or less with low-rates of mortality and relapsed infection at 90-days and notable savings in IV access and hospital days compared to treatment courses of 6 weeks. More research is needed to identify ways to mitigate patient directed discharges and reduce rates of readmission.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cem\u003eEthics approval and consent to participate\u003c/em\u003e: Approved by the University of Kentucky Institutional Review Board (IRB #71514). Patient consent was not required by the IRB.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConsent for publication:\u003c/em\u003e Patient consent was not required by the IRB.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAuthor contributions:\u003c/em\u003e All authors have had access to the manuscript and contributed to its composition.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAcknowledgments:\u003c/em\u003e Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eFunding:\u003c/em\u003e There was no funding for this manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eCompeting interests:\u003c/em\u003e The authors have no conflicts of interest to disclose.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eAvailability of data and materials:\u003c/em\u003e De-identified data can be made available upon request.\u0026nbsp;\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eClarelin A, Rasmussen M, Olaison L et al (2021) Comparing right- and left sided injection-drug related infective endocarditis. Sci Rep 11(1):1177\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoreillon P, Que YA (2004) Infective endocarditis. Lancet 363(9403):139\u0026ndash;149\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAlnabelsi TS, Sinner G, Al-Abdouh A et al (2023) The evolving trends in infective endocarditis and determinants of mortality: a 10-year experience from a Tertiary Care Epicenter. Curr Probl Cardiol 48(6):101673\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShmueli H, Thomas F, Flint N et al (2020) Right-Sided Infective Endocarditis 2020: Challenges and Updates in Diagnosis and Treatment. \u003cem\u003eJ Am Heart Assoc\u003c/em\u003e. ; 4;9(15):e017293\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDelgado V, Ajmone Marsan N, de Waha S, eta al (2023) 2023 ESC Guidelines for the management of endocarditis. 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Circulation 146(14):e187\u0026ndash;e201\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eIversen K, Ihlemann N, Gill SU et al (2019) Partial Oral versus Intravenous Antibiotic Treatment of Endocarditis. N Engl J Med 380(5):415\u0026ndash;424\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKinney EM, Vijapurapu S, Covvey JR et al (2021) Clinical outcomes of concomitant rifamycin and opioid therapy: A systematic review. Pharmacotherapy 41(5):479\u0026ndash;489\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRapoport AB, Fischer LS, Santibanez S et al (2018) Infectious Diseases Physicians' Perspectives Regarding Injection Drug Use and Related Infections, United States, 2017. 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Expert Rev Pharmacoecon Outcomes Res 17:355\u0026ndash;375\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eKimmel SD, Kim JH, Kalesan B et al (2021) Against Medical Advice Discharges in Injection and Non-injection Drug Use-associated Infective Endocarditis: A Nationwide Cohort Study. Clin Infect Dis 73(9):e2484\u0026ndash;e2492\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Dalati S, Paras ML, Strnad L et al (2023) In Plain Sight: The Need for a Dedicated Cardiovascular Infectious Disease Subspecialty. JACC Adv 3(1):100748\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Dalati S, Thornton A, Reda H et al (2024) Beyond a team: The comprehensive interdisciplinary endocarditis program in the United States. Int J Cardiol 397:131638\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Dalati S, Alnabelsi T, Gurley J et al (2024) Acute drug-use-related native tricuspid valve infective endocarditis: a non-surgical disease. Ther Adv Infect Dis 11:20499361241267124\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollis B, Alnabelsi T, Hall E et al (2024) Management of isolated native tricuspid valve infective endocarditis by a multidisciplinary program: a single-center retrospective cohort study. Ther Adv Infect Dis 11:20499361241280690\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHall E, Collis B, Alnabelsi T et al (2025) Management of Cardiovascular Implantable Electronic Device Infection Utilizing a Multidisciplinary Team: A Retrospective Cohort Study. Open Forum Infect Dis. ;ofaf148\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEl-Dalati S, Castillo MRC, Strnad L et al (2024) Shared Decision-Making for Partial Oral Antibiotic Treatment of Infective Endocarditis: A Case Series. Open Forum Infect Dis 11(4):ofae166\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMcDanel JS, Perencevich EN, Diekema DJ et al (2015) Comparative effectiveness of beta-lactams versus vancomycin for treatment of methicillin-susceptible Staphylococcus aureus bloodstream infections among 122 hospitals. Clin Infect Dis 61(3):361\u0026ndash;367\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMitaka H, Miyashita S, Yamada T et al (2019) Effectiveness of Beta-Lactams Versus Vancomycin for Treatment of Methicillin-Susceptible Staphylococcus aureus Bacteremia: A Systematic Review and Meta-Analysis. J Sci Innov Med 2(2):8\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eUlloa ER, Singh KV, Geriak M et al (2020) Cefazolin and ertapenem salvage therapy rapidly clears persistent methicillin-susceptible staphylococcus aureus bacteremia. 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J Gen Intern Med 37(10):2521\u0026ndash;2525\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAppa A, Adamo M, Le S et al (2022) Patient-Directed Discharges Among Persons Who Use Drugs Hospitalized with Invasive Staphylococcus aureus Infections: Opportunities for Improvement. Am J Med 135(1):91\u0026ndash;96\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWildenthal JA, Atkinson A, Lewis S et al (2023) Outcomes of Partial Oral Antibiotic Treatment for Complicated Staphylococcus aureus Bacteremia in People Who Inject Drugs. Clin Infect Dis 76(3):487\u0026ndash;496\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFort\u0026uacute;n J, Navas E, Mart\u0026iacute;nez-Beltr\u0026aacute;n J et al (2001) Short-course therapy for right-side endocarditis due to Staphylococcus aureus in drug abusers: cloxacillin versus glycopeptides in combination with gentamicin. Clin Infect Dis 33(1):120\u0026ndash;125\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Endocarditis, Right-sided endocarditis, MSSA bacteremia, Infections in people who inject drugs, Multidisciplinary teams","lastPublishedDoi":"10.21203/rs.3.rs-6498341/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6498341/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cem\u003eBackground: \u003c/em\u003eIsolated methicillin susceptible \u003cem\u003eStaphylococcus aureus \u003c/em\u003enative tricuspid valve endocarditis (MSSA TVIE) is a serious complication of injection drug use with significant associated morbidity and cost.\u0026nbsp; Guideline recommendations differ with respect to the optimal duration and route of antibiotic administration which can contribute to variations in clinical practice.\u0026nbsp; We report the outcomes of treating MSSA TVIE endocarditis using a multidisciplinary team and cardiovascular infectious diseases consult service.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eMethods: \u003c/em\u003ePatient cases were identified from an institutional multidisciplinary endocarditis team registry in a single-center retrospective study. Demographics, treatment and outcomes data were recorded by study investigators.\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eResults: \u003c/em\u003eBetween September 7th, 2021, and September 7\u003csup\u003eth\u003c/sup\u003e, 2024, 34 consecutive patients with definite isolated MSSA TVIE were identified.\u0026nbsp; Patients were treated with antibiotics for a median duration of 28 days (IQR 11 – 41) of which half were treated with oral antibiotics for a median duration of 14 days. During the follow up period there was one relapsed infection within 30 days and one death contributing to a 2.9% in hospital mortality \u0026amp; 90-day mortality. In the study population there were high rates of active injection drug use (79.4%), prior history of infectious endocarditis (23.5%), patient-directed discharge (35.3%). and 90-day readmissions (35.3%).\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eConclusion\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003eUtilizing a standardized approach to patient care, including a cardiovascular infectious diseases consult service and multidisciplinary endocarditis team, patients with MSSA isolated TVIE without metastatic osteoarticular or spinal infections were successfully treated with antibiotic courses of 28 days or less with low-rates of mortality and relapsed infection at 90-days.\u0026nbsp;\u003c/p\u003e","manuscriptTitle":"Antibiotic Treatment Duration for Isolated Methicillin-Susceptible Staphylococcus Aureus Native Tricuspid Valve Endocarditis: A Standardized Multidisciplinary Approach","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-13 11:47:13","doi":"10.21203/rs.3.rs-6498341/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"2324976a-37b8-4907-b11c-d0b2fb9ce35e","owner":[],"postedDate":"May 13th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2025-05-26T09:25:01+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-13 11:47:13","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6498341","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6498341","identity":"rs-6498341","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}