Enterococcal Infective Endocarditis Research Articles

Trends of Infective Endocarditis at Two Teaching Hospitals: A 12-Year Retrospective Cohort Study in Rio de Janeiro, Brazil.

Despite advances in diagnosis and treatment, the incidence and mortality of infective endocarditis (IE) have increased in recent decades. Studies on the risk factors for mortality in endocarditis in Latin America are scarce. This retrospective cohort study included 240 patients diagnosed with IE according to the modified Duke criteria who were admitted to two university hospitals in Rio de Janeiro, Brazil from January 2009 to June 2021. Poisson regression analysis was performed for trend tests. The multivariate Cox proportional hazards model was used to estimate the hazard ratio (HR) of predictors of in-hospital mortality. The median age was 55 years (IQR: 39-66 years), 57% were male, and 41% had a Charlson comorbidity index (CCI) score > 3. Healthcare-associated infective endocarditis (54%), left-sided native valve IE (77.5%), and staphylococcal IE (26%) predominated. Overall, in-hospital mortality was 45.8%, and mortality was significantly higher in the following patients: aged ≥ 60 years (53%), CCI score ≥ 3 (60%), healthcare-associated infective endocarditis (HAIE) (53%), left-sided IE (51%), and enterococcal IE (67%). Poisson regression analysis showed no trend in in-hospital mortality per year. The adjusted multivariate model determined that age ≥ 60 years was an independent risk factor for in-hospital mortality (HR = 1.9; 95% CI 1.2-3.1; p = 0.008). In this 12-year retrospective cohort, there was no evidence of an improvement in survival in patients with IE. Since older age is a risk factor for mortality, consensus is needed for the management of IE in this group of patients.

Enterococcal Infective Endocarditis – Post discharge treatment with continuous benzylpenicillin and ceftriaxone: A retrospective cohort study

BackgroundEnterococcal Infective Endocarditis (EIE) is usually treated with the combination of penicillin/ampicillin with gentamicin or ampicillin with ceftriaxone. To enable prolonged outpatient treatment, a combination of benzylpenicillin and ceftriaxone has been suggested. This study aimed to describe the incidence and characteristics of EIE and to determine the outcome of EIE cases treated with benzylpenicillin and ceftriaxone. MethodsThis was a retrospective single-center study including all patients diagnosed with infective endocarditis (IE) during 2016–2021, comparing EIE with IE caused by other pathogens. We described the outpatient treatment of patients with EIE, comparing those treated of benzylpenicillin - ceftriaxone with other regimes. ResultsAmong 222 patients with IE, 44 (20%) were diagnosed with EIE. Those were older, had a male predominance (p = 0.035), and were more disabled (p = 0.004). The incidence of EIE reached 30% towards the last year, becoming the leading etiology. Twenty-six patients received outpatient treatment, five of whom were discharged with benzylpenicillin and ceftriaxone. Adding patients from this cohort to the scarce data available, revealed similar recurrence and mortality rates compared to other treatment regimes. ConclusionsEIE is becoming a more frequent cause of IE, involving older, more disabled patients with male predominance. Our experience and existing literature suggest that the combination of benzylpenicillin and ceftriaxone is as safe as more conventional regimes, although further research is needed.

Amoxicillin therapeutic drug monitoring for endocarditis: A comparative study (EI-STAB)

IntroductionInternational guidelines recommend high doses of β-lactams for most cases of infective endocarditis (IE). Therapeutic drug monitoring (TDM) is increasingly used to adjust β-lactam dose based on plasma concentrations, although there are no comparative studies to support this practice. The benefit of amoxicillin TDM during IE was evaluated. MethodsAn observational, retrospective, cohort study of adults treated with high-dose amoxicillin for enterococcal or streptococcal IE was conducted in two referral centers. Patients with, or without TDM were compared. The primary outcome was mean daily amoxicillin dose. ResultsA total of 206 cases of streptococcal (n=140, 68%) or enterococcal (n=66, 32%) IE were included. IE occurred on prosthetic valves in 77 (37%) cases, and on intracardiac devices in 28 (14%) cases. Aortic valve was involved in 136 (66%) cases. There were 154 men (75%), mean age was 70 ± 14 years, valve surgery was performed in 81/206 (39%) patients, and in-hospital mortality was 8% (17/206). All patients in the TDM group and most patients in the group without TDM received amoxicillin as continuous infusion. Amoxicillin TDM was performed for 114 patients (55.3%), with a mean of 4.7 ± 2.3 measures per patient, a mean plasma steady-state concentration of 41.2 ± 19 mg/L, most (82/114, 72%) being within the therapeutic target (20–80 mg/L). Mean amoxicillin dose was lower in patients with TDM (10.0 ± 3.3 g/day) than those without TDM (11.3 ± 2.0 g/day) (P=0.003). ConclusionAmoxicillin TDM was associated with a reduction in daily doses, with no impact on adverse events and prognosis. Individualized treatment of IE through TDM may contribute to decreased use of antibiotics.

Adherence to 2015 ESC Guidelines for the Treatment of Infective Endocarditis: A Retrospective Multicentre Study (LEIOT Study).

Infective endocarditis (IE) is still a severe disease with elevated morbidity and mortality. Nevertheless, the last European guidelines (GL) date back to 2015, and a recent survey described a diffuse suboptimal adherence to their recommendations. Here, we described a real-life scenario about adherence to IE treatment GL. This was a retrospective, multicentric, case-control study. All the cases of IE admitted to our wards from 2016 to 2020 were enrolled. Patients were divided into two groups, according to the non-adherence (group A, cases) or adherence (group B, controls) to 2015 ESC guidelines. Only targeted treatments were considered. Groups were compared for demographic, clinical, microbiological, and laboratory data and outcome. As a post hoc analysis, we analysed the characteristics of deviations from the guidelines and how these deviations affected mortality. A total of 246 patients were enrolled, with 128 (52%) in group A and 118 (48%) in group B. Groups were homogeneous except for aetiologies: staphylococcal and blood-culture-negative IE were more frequent in group A, while streptococcal and enterococcal IE were more frequent in group B (p < 0.001). In-hospital mortality was comparable in the two groups. The most frequent causes of deviations from the guidelines were use of daptomycin, in addition to standard treatments and the missing administration of rifampin or gentamycin. Adherence to 2015 ESC guidelines was limited but it did not affect mortality.

1988. Piperacillin-tazobactam plus Ceftriaxone for Enterococcus faecalis endocarditis: A Single Center Experience

Abstract Background Enterococcus faecalis is a leading cause of Infective Endocarditis (IE). IE guidelines recommend combination of penicillin (PCN) or ampicillin (AMP) with ceftriaxone (CTX) in susceptible strains. OPAT allows for antibiotic continuation at home; however outpatient AMP is limited due to frequent dosing and instability. Piperacillin-tazobactam (PTZ) has similar but not identical activity against penicillin binding proteins (PBP) compared to AMP and PCN, suggesting that PTZ may be a substitute in OPAT. This study compares outcomes in those with E. faecalis IE discharged with either PTZ or PCN with CTX. Results of primary outcomes including death at 90 days and readmission at 90 days for those discharged on either PTZ or PCN in combination with CTX for E. faecalis endocarditis Results of non infectious complications and changes in antibiotic therapy in both groups post discharge Methods This single center retrospective study took place from 2016 - 2020. Adults &amp;gt; 18 years with AMP susceptible E. faecalis IE diagnosed using Duke’s criteria and blood or tissue cultures were included, with cultures confirming PCN susceptibility. Primary endpoint was failure of therapy at 90 days, defined as death due to any cause or infection relapse. Secondary outcomes were duration of antibiotics, change in regimen and non-infectious complications. Results Overall, 34 patients were identified, 17 in each group. Average age was 60–80 years, majority having a high Charleston comorbidity index. One did not have available AMP susceptibility but was PCN susceptible. 19 were managed surgically (65% PTZ group, 47% PCN group). Average total antibiotic course was 8.2 and 7.3 weeks in PTZ and PCN groups, with average OPAT course being 4.5 and 4.4 weeks. Primary endpoint was met in 18% patients in the PTZ group and 24% in the PCN group. Of the PCN group, 1 was admitted 4 months later due to an E. faecalis device infection, outside of primary endpoint. Nearly 80% completed antibiotic therapy with 29% in the PTZ group and 35% in the PCN group readmitted for non-infectious complications, including metabolic imbalances, stroke, volume overload and gastro-intestinal bleed. Hyperkalemia was seen in the PCN group with 3 patients requiring readmission. Seizures were not reported with combined PCN and ceftriaxone. Conclusion Similar outcomes were seen using either PTZ or PCN with CTX for treatment of enterococcal IE. Discharging patients on PCN is not always a feasible option. In these instances, PTZ could be considered as an alternative OPAT agent despite dissimilar mechanism of action compared to AMP and PCN. Disclosures All Authors: No reported disclosures.

Diffusion of amoxicillin into heart valves from infective endocarditis patients.

Amoxicillin is the drug of choice in the management of streptococcal and enterococcal infective endocarditis (IE) but little is known regarding amoxicillin diffusion into infected heart valves. Herein, we assessed amoxicillin valvular distribution and related pharmacokinetic/pharmacodynamic (PK/PD) target attainment in IE patients undergoing heart valve surgery. In this 2-year prospective study, patients with IE treated by continuous infusion of amoxicillin and undergoing a surgical valve replacement were included. Both amoxicillin plasma and tissue concentrations were measured the day of surgery. Amoxicillin concentration in plasma and crushed heart valves were measured by a validated liquid chromatography method coupled with ultra-violet and tandem mass spectrometry, respectively. MIC and MBC of amoxicillin were determined for all available isolates. The rate of achievement of PK/PD efficacy parameters were assessed. Twenty-two heart valves were removed from 20 patients. Bacterial aetiology was streptococcal (n = 17) and enterococcal (n = 3). Amoxicillin mean daily dose was 12 ± 3 g/24 h, mean plasma concentration was 29 ± 21 mg/L (n = 15), mean tissue concentration was 23 ± 15 mg/L (n = 22). Median diffusion rate was 62%. Patients reached a plasma concentration target >4XCMI (n = 13). Tissue concentrations were bactericidal for all streptococcal IE but not for enterococcal IE. Amoxicillin intravalvular measurements in IE treated patients showed significant penetration into the infectious site. These data are reassuring that in situ bactericidal concentrations can be largely achieved in the management of streptococcal IE and support the need for combination antibiotic therapy for enterococcal IE.

A Proof of Concept of the Usefulness of a TDM-Guided Strategy for Optimizing Pharmacokinetic/Pharmacodynamic Target of Continuous Infusion Ampicillin-Based Regimens in a Case Series of Patients with Enterococcal Bloodstream Infections and/or Endocarditis.

(1) Objective: To describe the usefulness of a real-time therapeutic drug monitoring (TDM)-based strategy for optimizing pharmacokinetic/pharmacodynamic (PK/PD) target attainment of continuous infusion (CI) ampicillin-based regimens in a case series of patients affected by suspected or documented enterococcal bloodstream infections (BSIs) and/or infective endocarditis (IE). (2) Methods: Patients treated with CI ampicillin-based regimens for documented or suspected enterococcal BSI/IE who underwent real-time therapeutic drug monitoring (TDM)-based expert clinical pharmacological advice (ECPA) between June 2021 and May 2022 were retrospectively assessed. Ampicillin concentrations were determined at steady state, and the free fraction (fCss) was calculated according to a plasma protein binding of 20%. The fCss/MIC ratio was selected as the PD parameter for ampicillin efficacy and was defined as optimal for values between 4 and 8. The requirement for TDM-guided ampicillin dosing adjustments was assessed. (3) Results: Data for 12 patients with documented (n = 10) or suspected (n = 2) enterococcal infections (7 with BSIs and 5 with IE) were retrieved. The ampicillin PK/PD target was optimal over time in all of the 10 documented infections. None of the enterococcal BSIs persisted. Following the first real-time TDM-based ECPA, ampicillin dosage was decreased by >50% in 11 out of 12 patients (91.7%). (4) Conclusions: CI may be helpful in attaining aggressive ampicillin PK/PD targets in patients affected by enterococcal BSIs and/or IE. Administration of CI ampicillin after loading coupled with real-time TDM-based ECPA could be a valuable strategy for managing enterococcal infections.

Beta Lactams Plus Daptomycin Combination Therapy for Infective Endocarditis: An Italian National Survey (BADAS).

Background: infective endocarditis (IE) remains a severe disease frequently encountered in clinical practice and often requiring interdisciplinary medical and surgical management. This national survey aims to describe the clinical prescribing habits of the use of daptomycin in the setting of IE and the possible role for combination therapy with beta-lactams. Methods: The study was a cross-sectional internet-based questionnaire survey on therapy with daptomycin. The questionnaire was designed with closed-ended questions and distributed using the SurveyMonkey® platform between October 2019 to December 2020. Results: 55 clinicians from twelve Italians regions joined the questionnaire. The survey reported use of daptomycin as first-line choice in 31.48% of cases and as the first-line anti-MRSA agent in 44.44%. The empiric use of daptomycin was stated in the high suspicion of MRSA rather than MSSA, enterococcal or streptococcal IE. The rationale of daptomycin for the empirical treatment of native and prosthetic valve IE was mostly the possibility of administering an aminoglycoside-sparing combination regimen, high bacterial killing rate and high clinical efficacy. Conclusions: In conclusion, in selected patients, daptomycin could be a feasible option for the treatment of infective endocarditis in line with data from the European registry of daptomycin.

Retraction: Enterococcal Infective Endocarditis following Periodontal Disease in Dogs.

Retraction: Enterococcal Infective Endocarditis following Periodontal Disease in Dogs.

Ampicillin-Ceftriaxone vs Ampicillin-Gentamicin for Definitive Therapy of Enterococcus faecalis Infective Endocarditis: A Propensity Score-Matched, Retrospective Cohort Analysis.

BackgroundAmpicillin-ceftriaxone (AC) has emerged as an alternative antibiotic regimen for enterococcal infective endocarditis (EIE) with reduced toxicity compared with ampicillin-gentamicin (AG), but evidence regarding its success in reducing EIE-associated death in the United States is limited.MethodsWe conducted a retrospective, propensity score–matched cohort analysis of EIE patients treated with AC or AG between 2010 and 2017 at 3 hospitals in Pittsburgh, Pennsylvania. We assessed all-cause 90-day mortality as the primary outcome and in-hospital mortality, length of hospital stay, hospital readmissions, adverse events, and relapse of bacteremia as the secondary outcomes.ResultsA total of 190 patients with EIE (100 treated with AC and 90 with AG) were included. Ninety-day mortality was significantly higher with AC than AG (21% vs 8%; P = .02). After propensity score matching, 56 patients in each group remained for the outcomes analysis. Documented aminoglycoside resistance, presence of annular or aortic abscess, and complete pacemaker removal were the significantly different variables between the 2 matched cohorts. We observed no statistically significant difference in 90-day mortality between the 2 treatment groups (11% vs 7%; P = .55). Adverse events were more common in patients treated with AG (25 vs 39; P = .0091), and more patients in the propensity score–matched AG cohort switched antibiotic regimens than in the AC group (10% vs 49%; P < .0001).ConclusionsPatients treated with AC demonstrate no significant differences in mortality, treatment failure, or bacteremia relapse compared with AG in a propensity score–matched EIE cohort.

Temporal Trends of Infective Endocarditis in Olmsted County, Minnesota, Between 1970 and 2018: A Population-Based Analysis.

BackgroundA population-based study of infective endocarditis (IE) in Olmsted County, Minnesota, provides a unique opportunity to define temporal and seasonal variations in IE incidence over an extended time period.MethodsThis was a population-based review of all adults (≥18 years) residing in Olmsted County, Minnesota, with definite or possible IE using the Rochester Epidemiology Project from January 1, 1970, through December 31, 2018. Poisson regression was used to characterize the trends in IE incidence; models were fitted with age, sex, calendar time, and season, allowing for nonlinearity and nonadditivity of their effects.ResultsOverall, 269 cases of IE were identified over a 49-year study period. The median age of IE cases was 67.2 years, and 33.8% were female. The overall age- and sex-adjusted incidence of IE was 7.9 cases per 100 000 person-years (95% CI, 7.0–8.9), with corresponding rates of 2.4, 2.4, 0.9, and 0.7 per 100 000 person-years for Staphylococcus aureus, viridans group streptococci (VGS), Enterococcus species, and coagulase-negative staphylococci IE, respectively. Temporal trends varied by age, sex, and season, but on average IE incidence increased over time (P = .021). Enterococcal IE increased the most (P = .018), while S. aureus IE appeared to increase but mostly in the winter months (P = .018). Between 1996 and 2018, the incidence of VGS IE was relatively stable, with no statistically significant difference in the trends before and after the 2007 AHA IE prevention guidelines.ConclusionsOverall, IE incidence, and specifically enterococcal IE, increased over time, while S. aureus IE was seasonally dependent. There was no statistically significant difference in VGS IE incidence in the periods before and after publication of the 2007 AHA IE prevention guidelines.

Enterococcal infective endocarditis is a marker of current occult or future incident colorectal neoplasia

Background: Few studies suggest an association between Enterococcal infective endocarditis (EIE) and colorectal disease, including colorectal neoplasia (CRN) and colorectal cancer (CRC). In this study, we analyze differences in prevalence, risk factors and outcome of CRN and CRC between EIE and Streptococcus gallolyticus infective endocarditis (SGIE). Methods: Single center, observational study of 166 patients with definite EIE or SGIE. Clinical data were collected prospectively in a standardized IE protocol. Colonoscopy data were collected retrospectively on 90 patients. Results: 85 patients had EIE, 81 SGIE. EIE patients had a higher rate of prior cancer (20% vs 6%) and health-care associated infection (12% vs 1%), but similar mortality than SGIE. Colonoscopy performed in 90 patients showed intestinal diseases in 30 of 42 (71%) EIE patients vs. 40 of 48 (83%) SGIE patients (p = 0.174), with a predominance of CRN. Among 78 patients who underwent colonoscopy after IE diagnosis, no difference between EIE and SGIE was observed in the rate of non-neoplastic lesions (48% vs 47%), benign (32% vs 40%) or malignant (13% vs 15%) neoplastic lesions. Adverse events during colonoscopy were uncommon, although a careful handling of anticoagulation was required. Conclusions: EIE seems to be associated with colorectal disease, including colorectal neoplasia and colorectal cancer, to the same extent as SGIE. EIE should be considered a marker of colorectal neoplasia, even in patients with a clear health-care related acquisition. Colonoscopy is generally safe in EIE patients, and should be considered to early diagnose and treat colorectal disease.

A RARE CASE OF NATIVE TRIPLE-VALVE INFECTIVE ENDOCARDITIS

SESSION TITLE: Medical Student/Resident Cardiovascular Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Infective endocarditis (IE) is a life-threatening infection. Despite medical advances, mortality from IE remains high. Enterococcal IE is becoming more prevalent in elderly patients with degenerative valvular disease and bloodstream infections from gastrointestinal (GI) or genitourinary (GU) tracts. We present a rare case of native triple-valve infective endocarditis. CASE PRESENTATION: A 58-year-old man with a history of squamous cell carcinoma of tongue post hemiglossectomy with chemoradiation therapy and small bowel obstruction post open laparotomy a month earlier presented for altered mental status. Initial vitals showed tachycardia and was otherwise normal. Positive examination findings were cachexia, a healed partial tongue resection, decreased air entry over lung bases and left upper abdominal tenderness without peritonitis. The rest of the physical exam was unremarkable. Initial lab results were significant for leukocytosis, mild anemia, elevated BUN and creatinine. Computed tomography (CT) of chest and abdomen showed a large left lower lobe consolidation, right lower lobe patchy parenchymal disease and gastric wall thickening. He was started empirically on Zosyn, vancomycin and fluconazole. Blood cultures grew Enterococcus faecalis and transthoracic echocardiogram (echo) showed an acute-on-subacute endocarditis with vegetations on the tricuspid, mitral and aortic valves with ejection fraction 65-70%. Bronchoscopy with bronchoalveolar lavage (BAL) culture was positive for Candida Glabrata 3 days after his death. He later developed septic shock with multiorgan failure and was considered ineligible for surgery. Despite optimal medical therapy and no worsening of echo findings, he ultimately died. DISCUSSION: Multivalvular IE increases the likelihood of complications from congestive heart failure, acute renal failure, embolic events, disseminated intravascular anticoagulation and death (1). Enterococcus faecalis is an opportunistic pathogen in oral cavity, the GI and GU tracts. Manipulation of the GI and GU tracts, cancer and previous treatment with antibiotics increase the risk of enterococcal bacteremia. Our patient’s overall immunocompromised state and recent surgical intervention placed him at higher risk of Enterococcus faecalis infection. Enterococcus faecalis bacteremia is a common cause of IE that has had no survival improvement in the past decade (2). Ultimately, his BAL culture was positive for Candida glabrata, which if resulted in fungemia, could be complicated by a rare but aggressive form of IE with a mortality rate of 80% requiring both medical and early surgical intervention (3). CONCLUSIONS: Triple valve endocarditis is rare with few studies in literature to guide the best management. Further research is necessary to identify patients at increased risk of multivalve IE, in regards to optimal screening methods to facilitate early detection and therapy. Reference #1: Kim, N., Lazar, J., Cunha, B., Liao, W., & Minnaganti, V. (2000). Multi-valvular endocarditis. Clinical Microbiology and Infection, 6(4), 207–212. doi: 10.1046/j.1469- 0691.2000.00065.x Reference #2: Dahl, A., Rasmussen, R. V., Bundgaard, H., et al. (2013). Enterococcus faecalis Infective Endocarditis. Circulation, 127(17), 1810–1817. doi: 10.1161/circulationaha.112.001170 Reference #3: Baddley, J. W., Benjamin, D. K., et al. (2008). Candida infective endocarditis. European Journal of Clinical Microbiology & Infectious Diseases, 27(7), 519–529. doi: 10.1007/s10096-008-0466-x DISCLOSURES: No relevant relationships by Sahai Donaldson, source=Web Response No relevant relationships by Lorenzo Leys, source=Web Response No relevant relationships by Alem Mehari, source=Web Response No relevant relationships by Lamiaa Rougui, source=Web Response

Infective Endocarditis Guidelines: The Challenges of Adherence-A Survey of Infectious Diseases Clinicians.

BackgroundGuidelines exist to aid clinicians in managing patients with infective endocarditis (IE), but the degree of adherence with guidelines by Infectious Disease (ID) physicians is largely unknown.MethodsAn electronic survey assessing adherence with selected IE guidelines was emailed to 1409 adult ID physician members of the Infectious Diseases Society of America’s Emerging Infections Network.ResultsFive hundred fifty-seven physicians who managed IE responded. Twenty percent indicated that ID was not consulted on every case of IE at their hospitals, and 13% did not recommend transthoracic echocardiography (TTE) for all IE cases. The duration of antimicrobial therapy was timed from the first day of negative blood cultures by 91% of respondents. Thirty-four percent of clinicians did not utilize an aminoglycoside for staphylococcal prosthetic valve IE (PVE). Double β-lactam therapy was “usually” or “almost always” employed by 83% of respondents for enterococcal IE. For patients with active IE who underwent valve replacement and manifested positive surgical cultures, 6 weeks of postoperative antibiotics was recommended by 86% of clinicians.ConclusionsThe finding that adherence was <90% with core guideline recommendations that all patients with suspected IE be seen by ID and that all patients undergo TTE is noteworthy. Aminoglycoside therapy of IE appears to be declining, with double β-lactam regimens emerging as the preferred treatment for enterococcal IE. The duration of postoperative antimicrobial therapy for patients undergoing valve replacement during acute IE is poorly defined and represents an area for which additional evidence is needed.

Valve surgery for infective endocarditis complicated by stroke: surgical timing and perioperative neurological complications.

Ischaemic and hemorrhagic strokes are dreaded complications of infective endocarditis (IE). The timing of valve surgery for IE patients with stroke remains uncertain. The aim was to study perioperative neurological complications in relation to surgical timing. The study cohort consisted of patients diagnosed with acute IE from January 2010 to December 2016. Early surgery was defined as valve surgery within 14days of IE diagnosis, and late surgery as after 14 days. Neurological complications that occurred within 14days post-surgery were considered perioperative and classified as new ischaemic stroke or hemorrhagic stroke, expansion of an existing intracranial hemorrhage and new-onset seizures. Perioperative neurological complications were compared by surgical timing and other variables, including pre-surgical imaging. Overall, 183 patients underwent valve surgery: 92 had early surgery at a median of 8days (interquartile range 6-11); 91 had late surgery at a median of 28days (interquartile range 19-50). Twenty patients (10.9%) had 24 complications: 11 ischaemic, six intraparenchymal hemorrhages, three subarachnoid hemorrhages (SAHs) and four new-onset seizures. Rates of neurological complications were similar for early and late surgery groups (10.9% vs. 11%). Enterococcal IE was more common amongst patients with perioperative neurological complications (35% vs. 12.3%, P<0.01). An acute infarct was present on pre-surgical magnetic resonance imaging of 134 patients (74%) and was not associated with perioperative neurological complications. Thirty-five patients (19.3%) had intracranial hemorrhage on pre-surgical imaging. SAH on pre-surgical imaging was associated with developing SAH perioperatively (66.7% vs. 13.5%, P<0.01). Early valve surgery for patients with IE complicated by stroke was not associated with perioperative neurological complications.

Development and validation of a dosing nomogram for amoxicillin in infective endocarditis.

Amoxicillin is the first-line treatment for streptococcal or enterococcal infective endocarditis (IE) with a dose regimen adapted to weight. Covariates influencing pharmacokinetics (PK) of amoxicillin were identified in order to develop a dosing nomogram based on identified covariates for individual adaptation. Patients treated with amoxicillin administered by continuous infusion for IE were included retrospectively. The population PK analysis was performed using the Pmetrics package for R (NPAG algorithm). Influence of weight, ideal weight, height, BMI, body surface area, glomerular filtration rate adapted to the body surface area and calculated by the CKD-EPI method (mL/min), additional ceftriaxone treatment and serum protein level on amoxicillin PK was tested. A nomogram was then developed to determine the daily dose needed to achieve a steady-state free plasma concentration above 4× MIC, 100% of the time, without exceeding a total plasma concentration of 80 mg/L. A total of 160 patients were included. Population PK analysis was performed on 540 amoxicillin plasma concentrations. A two-compartment model best described amoxicillin PK and the glomerular filtration rate covariate significantly improved the model when included in the calculation of the elimination constant Ke. This work allowed the development of a dosing nomogram that can help to increase achievement of the PK/pharmacodynamic targets in IE treated with amoxicillin.

Efficacy of Primary Surgical Versus Medical Intervention for Treatment of Left-Sided Infective Endocarditis

Left-sided staphylococcal, streptococcal, and enterococcal infective endocarditis (IE) is associated with poor clinical outcomes. Our primary aim is to compare clinical outcomes of staphylococcal, streptococcal, and enterococcal IE patients who undergo valve replacement surgery and outcomes of patients who are treated solely with antibiotics. All patients were treated medically or surgically for left-sided staphylococcal, streptococcal, or enterococcal IE at our institution from 1998 to 2014 and were retrospectively studied. The primary outcome of interest was 30-day and 1-year mortality, and secondary outcomes included posttreatment septic shock, embolic events, stroke, and end-stage renal disease at 30 days. Inverse probability treatment weights, derived from propensity scores, were used to balance the medical and surgical cohorts across clinical risk factors, The Society of Thoracic Surgeon scores, and pathogens. Outcomes were compared comprehensively and in a staphylococcal-only subanalysis. Study population consisted of 245 surgical patients and 164 medical patients. Mortality at 30 days was higher in the medical cohort, both in aggregate and for staphylococcal only (all, 7% vs 16%, P < .001; staphylococcal only, 7% vs 22%, P < .001). Surgical patients had a higher incidence of septic shock and renal dysfunction; however, stroke and embolic events at 30 days were not different between cohorts. Cox survival analysis demonstrated that surgical treatment provided a 1-year survival benefit, with a hazard ratio of 0.48 (95% confidence interval, 0.36 to 0.64) that was robust regardless of pathogen. Compared with medical management, valve replacement surgery in patients with left-sided staphylococcal, streptococcal, or enterococcal IE appears to confer a survival advantage at 30 days and 1 year.

Infective endocarditis in French Polynesia: Epidemiology, treatments and outcomes

French Polynesia is a French overseas collectivity in the South Pacific Ocean, where data on infective endocarditis (IE) are lacking. To investigate the epidemiology and outcomes of IE in French Polynesia. All hospital records from consecutive patients hospitalized in Taaone Hospital, Tahiti, from 2015 to 2018, with an International Classification of Diseases, 10th revision, separation diagnosis of IE (I330), were reviewed retrospectively. From 190hospital charts reviewed, 105patients with a final diagnosis of IE, confirmed according to the modified Duke criteria, were included. The median duration of follow-up was 71days (interquartile range 18-163days). The mean age was 55±17years, and there were 68 men (65%). Thirty-five patients (33%) had a history of rheumatic carditis and 43 (41%) had a prosthetic valve. There were 40 (38%) cases of staphylococcal IE, 32 (30%) of streptococcal IE and six (6%) of enterococcal IE. Cardiogenic shock, septic shock and clinically relevant cerebral complications were strongly associated with death from any cause (hazard ratio [HR] 16.85, 95% confidence interval [CI] 5.45-52.05 [P<0.001]; HR 2.62, 95% CI 1.23-5.56 [P=0.01]; and HR 4.14, 95% CI 1.92-8.92 [P<0.001], respectively). Seventy-three patients (69%) had a theoretical indication for surgery, which was performed in 38 patients (36%). Lack of surgery when there was a theoretical indication was significantly associated with death (HR 6.93, 95% CI 3.47-13.83; P<0.0001). The pattern of IE in French Polynesia differs from Western countries in many ways. Postrheumatic valvular disease remains the main underlying disease, and access to emergency heart surgery is still a challenge.

Tempestuous Course of Enterococcus Infective Endocarditis — From Daptomycin Lung Toxicity to Successful Treatment With Surgery and Fosfomycin Combination Therapy

Abstract Management of enterococcal infective endocarditis (IE) is one of the intriguing challenges in infectious diseases. Ampicillin with gentamicin is the standard therapy for susceptible Enterococcus faecalis. However, in presence of β-lactam-resistant isolates, nephroxicity, or allergy to β-lactams, alternatives like glycopeptides and daptomycin have been used for the treatment of enterococcus IE. We report a patient with E. faecalis IE who had allergy to β-lactam and during treatment had developed daptomycin lung toxicity. He was subsequently treated with intravenous fosfomycin and surgery with aortic valve replacement.

P3666Spondylitis: a frequent and severe complication of infective endocarditis

Abstract Background Spondylodiscitis (SP) is a rare, but severe complication of infective endocarditis (IE). The incidence, clinical features and prognosis of SP in IE are unknown. Purpose The primary objective of our study was to assess the incidence, epidemiology, clinical presentation, prognosis, and therapeutic implications of SP in patient with IE. The secondary objectives were to assess factors associated with occurrence of spondylitis and to assess the value of imaging techniques. Methods In a French bi-center prospective study of patients who presented in our endocarditis reference centers with a diagnosis of definite IE from 1990 to 2018 (n=1755), 150 (8.5%) presented with SP. Clinical, epidemiological, microbiological, and prognostic variables were prospectively recorded and compared between patients with (n=150) and without (n=1605) SP. Results Patients with SP were older (mean age 69.7±18 vs 66.2±14; p=0.004), had more arterial hypertension (48% vs 34,5%; p&lt;0.001) and autoimmune disease (5% vs 2%; p=0.03) than patients without SP. The lumbar vertebrae were the most frequently involved (84 patients, 66%), especially L3-L4. Neurological symptoms were observed in 59% of patients. Enterococci et Gallolyticus streptococci were more frequent (24% vs 12% and 24% vs 11%; p&lt;0,001, respectively) in the SP group. Observed sensitivities of full spine contrast-enhanced MRI and CT were 95% and 89%, respectively. PET/CT had a great power to differentiate infective to degenerative vertebral processes, and to find embolic foci with a sensitivity of 90%. Clinical outcome did not differ between patients with or without SP, including similar in-hospital mortality (16% vs 13,5%, p=0.38). Conclusions We describe the largest ever reported series of patients with spondylodiscitis complicating IE. Spondylodiscitis is a more frequent complication of IE than previously reported (8.5% of IE), is observed in older hypertensive patients with Enterococcal or Streptococcus gallolyticus IE and has a similar prognosis than other forms of IE. Since SP is associated with prolonged antibiotic therapy and may need specific surgical therapy, multimodality imaging including MRI, CT, and PET/CT should be used for early diagnosis of this IE complication.