Cause Of Infective Endocarditis Research Articles

Complex pathogens in infective endocarditis

Infective endocarditis (IE) is a complex disease whose prognosis depends on the causative microorganism, among other factors. The latter can be difficult to identify and/or treat. In this narrative review, we identify knowledge gaps in the diagnosis and antimicrobial treatment of IE, and attempt to shed light on current questions. Specifically, we: (1) analyze the factors that may hinder the microbiological diagnosis of blood culture-negative IE, as well as the role of new imaging techniques, such as 18F-fluorodeoxyglucose ([18F]FDG PET/CT), in the diagnostic capacity of this disease, understanding their advantages and assuming their limitations; (2) discuss the therapeutic approach to various difficult-to-treat microorganisms. In particular, we focus on the treatment of staphylococcal IE since, at present, staphylococci are the most frequent cause of IE in developed countries and staphylococcal IE is one of those with the highest short- and long-term mortality. We critically evaluate the current evidence on combination therapy and address the occurrence of serious side effects, an aspect that is often overlooked owing to the severity of the infection; and (3) emphasize the need for home antimicrobial treatment of patients with IE, as these are fragile people who benefit from an early return to their environment. This poses undoubted logistical challenges and requires robust evidence to ensure the best short- and long-term outcomes.

Medical management of Pseudomonas aeruginosa endocarditis: A case report

Background: Pseudomonas aeruginosa is a rare cause of infective endocarditis. There is no standard treatment regimen for the management of infective endocarditis caused by this organism. Pseudomonas aeruginosa produces biofilm on the endocardial surface which can be difficult to eradicate, and monotherapy with a traditional beta-lactam agent may fail due to inadequate penetration into biofilm and low or absent activity on non-dividing cells. Prolonged courses and surgical intervention may be required to treat this infection. Case Description: A case of infective endocarditis caused by P. aeruginosa which showed inadequate response to beta-lactam plus beta-lactamase-inhibitor therapy and was later successfully managed without surgical intervention but a combination of a beta-lactam and an aminoglycoside is described here. This case which was treated with amikacin was followed up for ototoxicity. Ototoxicity is an irreversible side effect of amikacin and close follow-up with serial audiograms is required during therapy, especially when therapeutic drug monitoring is not possible. Conclusion: A combination regimen of a beta-lactam active against P. aeruginosa plus an aminoglycoside for a duration of four weeks can be an effective treatment for infective endocarditis caused by P. aeruginosa. Periodic monitoring for adverse drug events should be undertaken during therapy.

A case report of Gemella sanguinis isolated from blood cultures of a patient with mitral valve prolapse

Gemella sanguinis is a gram-positive, facultatively anaerobic coccus bacterium that has rarely been reported as a cause of infective endocarditis. A 41-year-old male patient with mitral valve prolapse visited the outpatient clinic presenting with fever. Transthoracic echocardiography and transesophageal echocardiography revealed myxomatous change and vegetation of the mitral valve. We isolated G. sanguinis from the patient’s blood, cultured it in both aerobic and anaerobic blood culture bottles, and identified it using matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS; bioMérieux, France) and 16s rRNA sequencing. The isolated G. sanguinis was highly susceptible to penicillin and vancomycin and intermediately susceptible to erythromycin, clindamycin, and levofloxacin. Following the American Heart Association recommendations, this highly penicillin-sensitive isolate was eradicated with ceftriaxone and gentamicin, and the patient recovered and was discharged. To the best of our knowledge, this is the first reported case in Korea where G. sanguinis, the causative agent of endocarditis, was identified using MALDI-TOF MS and 16s rRNA sequencing and was treated with only antibiotics and without surgical valve replacement.

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 > 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.

1980. A Case Series of Serratia Marcescens Endocarditis in Persons Who Inject Drugs

Abstract Background Serratia marcescens is a gram-negative bacillus that is widespread in the environment and has been recognized as a rare cause of infective endocarditis (IE), particularly in persons who inject drugs (PWID). The literature consists of a 19 person case series in the 1970s followed by just a handful of case reports and small case series. At AHWFB (Atrium Health Wake Forest Baptist), we have noticed an increasing number of severe infections, including IE, with Serratia marcescens in PWID. Methods We conducted a retrospective chart review of all cases of Serratia grown from sterile culture sites in the AHWFB system between 8/1/2016 -10/31/2021. Charts were reviewed to confirm status of injection drug use in the 3 months prior to admission, ≥18 years old, and possible or definite IE by Modified Duke’s criteria. Results Twenty two participants were included in the study. The median age was 29.5 years. Eighteen (90%) were white and 16 (73%) were female. Sixteen (73%) had injection of opioids and 3 (14%) had injection of stimulants clearly indicated. Ten (45.5%) had stimulant use documented but the route was not clear. Nineteen (95%) had evidence of active or resolved HCV infection. The median duration of bacteremia was 2 days. Two cases of IE involved the aortic valve, 8 mitral, 3 pulmonic, and 10 tricuspid. Four (18%) of the participants had prosthetic valve IE. Nine (41%) of the participants had a history of previous IE episode. Eighteen participants had evidence of septic emboli: 10 pulmonary, 7 cerebral, and 5 major arterial. In terms of disposition, 4 (18%) patients died, 4 left against medical advice, 12 (54%) remained at a facility for the duration of their antibiotics. One patient was transferred to another facility and one was discharged to complete antibiotic therapy via peripheral IVs in an infusion center. Two patients expired before a final antibiotic regimen could be determined. Ten participants were treated with beta lactam monotherapy, 1 with fluoroquinolone monotherapy, and 9 with dual therapy with a beta lactam and fluoroquinolone. Conclusion Serratia marcescens, a rare cause of IE, has been found in a population of PWID in a North Carolina hospital system. More research is necessary to understand why this unusual infection is clustering in this population and the optimal treatment regimen. Disclosures All Authors: No reported disclosures.

Granulicatella adiacens infective endocarditis

Infective endocarditis is an unconventional infectious disease nonetheless life-threatening. A roundabout of 3% to 5% cases of Streptococcal infective endocarditis is caused by nutritionally variant Streptococci (NVS). Granulicatella species is one of the atypical causes of infective endocarditis. In this context, the authors are disclosing a case of infective endocarditis in an underlying rheumatic heart disease patient, caused by Granulicatella adiacens. The patient had breathlessness for the past four months, on and off fever for two months anew and mid-diastolic murmur with vegetation in aortic valve as appeared by echocardiogram. The blood cultures were tested positive for Granulicatella adiacens. The patient was successfully treated with intravenous vancomycin for a period of six weeks.

Platelet Activation and Aggregation Induced by Streptococcus bovis/Streptococcus equinus Complex.

Streptococcus bovis/Streptococcus equinus complex (SBSEC) is a common cause of infective endocarditis (IE). For IE-pathogens, the capacity to activate and aggregate platelets is believed to be an important virulence mechanism. While the interactions between bacteria and platelets have been described in detail for many Gram-positive pathogens, little research has been carried out with SBSEC in this respect. Twenty-six isolates of the four most common species and subspecies of SBSEC identified in bacteremia were collected, and interactions with platelets were investigated in platelet rich plasma (PRP) from three donors. Aggregation was studied using light-transmission aggregometry and platelet activation using flow cytometry detecting surface upregulation of CD62P. Platelets and serum were treated with different inhibitors to determine mechanisms involved in platelet aggregation and activation. Twenty-two of 26 isolates induced aggregation in at least one donor, and four isolates induced aggregation in all three donors. In PRP from donor 1, isolate SL1 induced a rapid aggregation with a median time of 70 s to reach 50% aggregation. Blockade of the platelet Fc-receptor or enzymatic cleavage of IgG abolished platelet activation and aggregation. The capacity for bacteria-induced platelet aggregation was also shown to be transferable between donors through serum. SBSEC mediates platelet aggregation in an IgG and IgG-Fc-receptor dependent manner. Bacterial activation of platelets through this pathway is common for many bacteria causing IE and could be a potential therapeutic target for the prevention and treatment of this infection. IMPORTANCE The capacity of bacteria to activate and aggregate platelets is believed to contribute to the pathogenesis of IE. The Streptococcus bovis/Streptococcus equinus complex (SBSEC) contains known IE-pathogens, but there is limited research on the different subspecies ability to interact with platelets and what signaling pathways are involved. This study reports that 22 of 26 tested isolates of different subspecies within SBSEC can induce aggregation, and that aggregation is host dependent. The Fc-IgG-receptor pathway was shown essential for platelet activation and aggregation. To the best of our knowledge, this is the first study that reports on platelet interactions of SBSEC-isolates other than Streptococcus gallolyticus subspecies gallolyticus as well as the first study to report of mechanisms of platelet interaction of SBSEC-isolates. It adds SBSEC to a group of bacteria that activate and aggregate platelets via the platelet Fc-receptor. This could be a potential therapeutic target for prevention of IE.

Abstract 14458: It Takes Three to Tango: A Case of Occult Streptococcus Gordonii Infectious Endocarditis After Dental Cleaning Identified by History, Multi-Modal Imaging, and a Multi-Disciplinary Effort

Introduction: We present a case of a 65 year-old man with severe aortic regurgitation requiring a stented 23mm Edwards bioprosthetic aortic valve (BioAVR), who presented with 3-months of fevers and fatigue found to have Streptococcus gordonii ( S. gordonii ) infectious endocarditis (IE). He underwent dental cleaning 3-months prior sans prophylactic antibiotics. An echocardiogram on admission revealed increased peak/mean systolic gradients across the BioAVR to 46/26mmHg compared to gradients one year prior (32/19mmHg). Initially, a vegetation was not visualized by transthoracic echocardiogram (TTE) despite radiographic evidence of multi-organ emboli. Serial TTEs and transesophageal echocardiograms (TEEs) were performed due to persistent symptoms. Eventually, a new vegetation was visualized by TEE. A team effort involving cardiology, infectious disease, neurology, and cardiac surgery was required for management. Revision of the BioAVR was not pursued due to resolution of the vegetation. The patient was discharged after a prolonged hospitalization with recommendations to take amoxicillin 2g prior to future dental work. Results: Figure 1. A new 0.5cm vegetation visualized by TEE (A) with enlargement to 0.8cm (B), followed by a healed vegetation (C), and resolution 7-months later. Conclusions: S. gordonii has historically been a rare cause of IE therefore requiring a high clinical suspicion for diagnosis. Approximately 8% of IE cases are caused by streptococci. However, a recent study in Denmark on streptococci IE implicated S. gordonii in 44.2% of IE cases . S. gordonii is a gram-positive cocci found in oral flora known to cause subacute bacterial endocarditis. Our case highlights the importance of detailed history-taking to identify sources of infection, serial multi-modal imaging evaluation despite initial negative findings particularly with persistent clinical symptoms, and a multidisciplinary approach to IE cases due to multi-organ involvement.

Abstract 14609: Exposure to Any Hospitalization and Specific Invasive Procedures Post Open Heart Valve Surgery Increases the Risk of Endocarditis

Introduction: Infective endocarditis (IE) after cardiac valve surgery is associated with high morbidity and mortality. Nosocomial exposure is a growing cause of IE in general. We investigated the risk of post valve surgery endocarditis (PVE) in patient who had any hospitalization and specific nosocomial exposures after open heart valve surgery. Methods: We identified all ≥18yo patients who had their first open heart cardiac valve surgery between 2001-2017 in New South Wales, Australia from the Admitted Patient Data Collection (APDC) registry. Patients with prior/current IE diagnosis at time of index valve surgery were excluded. Follow up was until 31 Dec 2018 with mortality and morbidity tracked from the respective death and APDC registries. Analyses based on Cox regression modelling included age, sex, background diagnoses and features of index valve surgery as time independent covariates, with any hospitalization (separately for specific invasive procedures) post index valve surgery as time dependent exposure covariates for risk of PVE within 6 months of exposure. Results: In total 23747 patients (median age [IQR] 73yo [65-79yo, 63% male) had cardiac valve surgery: 60% isolated aortic valve (n=15065), 28% isolated mitral valve (n=6702), 10% multiple valves (n=2385) and 1.5% right sided valves (n=357). 5.4% (n=1293) of patients experienced PVE at a median 2.9 years (IQR 0.7-6.2) after index valve surgery, with 65% (n=838) occurring within 6 months of any hospitalization. Any hospitalization exposure was associated with an adjusted hazard ratio of 4.0 for developing PVE (95% confidence interval 3.5-4.5). In addition, specific invasive procedures including repeat valve surgery were associated with an elevated risk for PVE (Figure). Conclusions: PVE is significantly more common after any hospitalization with specific invasive procedures carrying differential risk. Care should be taken to avoid unnecessary hospitalizations and procedures in these patients.

Epidemiology of infective endocarditis in intravenous drug users

Recently, five North American studies have reported 471 persons who injected drugs intravenously (PWID) (25.34%) out of a total of 1858 patients with infective endocarditis (IE) and three European studies have reported 263 PWID out of 1225 patients with IE (21.46%). Both in North America and Europe the mean age of PWID with IE was 32-38 years and 41-44 years, respectively. Both in North America and in Europe Staphylococcus aureus was the leading cause of IE in PWID (67.30% and 66.15%, respectively). IE involves the tricuspid valve in 90% of cases and mitral and/or aortic valves in less than 15% of cases; the mortality rate is 2.0-2.5%. In North America and in Europe, streptococci caused IE in 10.61% and 10.64% of PWID, respectively, enterococci in 6.58% and 9.50%. Other etiologies accounted for 1-2%. Almost 6% of North American cases and almost 10% of European cases were polymicrobial. New episodes (25-32%) were mostly reinfections (up to 86.4%). PWID's in-hospital mortality was not significantly different from non-PWID's. Ten-year survival of PWID and non-PWID with IE was comparable in an American surgical study (69.5% vs 68.7%) and significantly different in a British study (43.8% vs 83.5%).

Granulicatella elegans infective endocarditis: A case report

Granulicatella elegans is a rare cause of infective endocarditis, accounting for 1–2% of all cases. It is well recognized that this pathogen can present in association with negative blood cultures. There are higher rates of both relapse and mortality compared with endocarditis caused by other bacteria. Microbiological diagnosis can be especially challenging because many conventional blood culture media lack pyridoxal, which can be found in automated blood culture broths like BACTEC™ or BACT/ALERT® and thus they may require ‘helper’ bacteria to be culture the organism. This current case report describes a 66-year-old male patient with a 10-year history of post-inflammatory combined aortic valve disease (moderate aortic stenosis and mild aortic regurgitation). He presented with a 3-month history of recurrent fever and general deterioration. Despite targeted, prolonged, combined antibiotic treatment with intravenous penicillin and gentamicin, surgery was eventually required. An aortic prosthetic valve implantation was performed with good results. In case of subacute endocarditis, especially when a causative organism proves difficult to detect, G. elegans should be considered. Identification is greatly enhanced by using polymerase chain reaction methods and this test should be considered in all cases of culture negative endocarditis.

Infective Endocarditis Caused by Granulicatella elegans in a Child With Patent Ductus Arteriosus.

To the editors: Infective endocarditis (IE) is an inflammatory process of infectious origin that affects cardiovascular structures. The term endarteritis is currently included in the definition of infective endocarditis. Granulicatella elegans is a rare cause of infective endocarditis, which has a subacute presentation of the disease, with nonspecific symptoms and mild elevation of inflammatory biomarkers. It is associated with a high-mortality rate in adults.1 In the pediatric age group, there are 3 cases of IE described by Granulicatella spp., associated with congenital heart disease: 1 with pulmonary atresia with intact interventricular septum and mild Ebstein’s malformation already operated,2 another one with Shone’s syndrome and the last one with infundibular pulmonary stenosis.1 Our case represents the fourth case worldwide with IE caused by Granulicatella spp., in congenital heart disease, and the first with patent ductus arteriosus (PDA). We report an 8-year-old female patient with a history of PDA was diagnosed at another hospital at 3 years of age. She was referred from another hospital with a 7-month history of fever, predominantly during the evening, between 38.4°C and 38.6°C. On admission hyperdynamic precordium with thrill, normal S2, left infraclavicular continuous murmur grade 4/6, slightly grainy sound, calling attention to a metallized acoustic component and wide pulses. Three blood cultures tested positive after 48 hours. Gram staining of the blood culture revealed Gram-positive cocci, that were, nonsporulating in pairs and short chains and, pleomorphic (Fig. 1A). Blood cultures were identified with Granulicatella elegans nutritionally variant streptococci using a commercial kit MALDI Sepsityper (Bruker Daltonics). Little growth on sheep-blood agar in a microaerophilic atmosphere after 72 hours.FIGURE 1.: A. Gram staining showing Gram-positive cocci, nonsporulating in pairs and, short chains, pleomorphic. B, (day 30) TTE. Parasternal 2D short axis view and color Doppler showing PDA with left to right shunt and hyperechogenic mass (green arrow) in the PA following the flow of the ductus. PA, pulmonary artery; PDA, patent ductus arteriosus; TTE, transthoracic echocardiogram.Vegetations were not found on the transthoracic echocardiogram (TTE) at admission, but after 30 days reveled; image suggestive of vegetation attached the pulmonary trunk (13 mm × 3 mm) (Fig. 1B). After completing 40 days of ceftriaxone, the vegetation was removed percutaneously, on the 58th day, the PDA was closed with Amplatzer ADO 8/6. Despite advances in diagnosis and treatment, infective endocarditis in the 21st century can be a life-threatening disease with high morbidity and mortality.1 Cyanogenic congenital heart disease, left heart lesions and atrioventricular defects are associated with an increased risk of IE in childhood.3 In children, the most frequent microorganism in subacute IE is Streptococcus viridans group4; however, in the second group nutritionally variant Streptococcus species (NVS) have been identified as etiological agents responsible for 5% of the cases with bacteriologic diagnosis.5 Physicians should suspect subacute IE in patients presenting with intermittent fever of prolonged evolution, constitutional symptoms, and changes in auscultatory phenomena in the context of children with congenital heart disease, despite having negative initial blood culture and absence of initial IE findings on echocardiogram. Granulicatella spp., IE has a subacute presentation with a mild increase in inflammatory biomarkers, and its morbidity and mortality can be significant. The modified Duke criteria are of great value; however, in some patients with subacute IE the diagnosis can be missed, therefore, the clinical features should be considered when a patient has a fever of unknown origin.

Activation of Human Platelets by Staphylococcus aureus Secreted Protease Staphopain A.

Infection by Staphylococcus aureus is the leading cause of infective endocarditis (IE). Activation of platelets by this pathogen results in their aggregation and thrombus formation which are considered to be important steps in the development and pathogenesis of IE. Here, we show that a secreted cysteine protease, staphopain A, activates human platelets and induces their aggregation. The culture supernatant of a scpA mutant deficient in staphopain A production was reduced in its ability to trigger platelet aggregation. The platelet agonist activity of purified staphopain A was inhibited by staphostatin A, a specific inhibitor, thus implicating its protease activity in the agonism. In whole blood, using concentrations of staphopain A that were otherwise insufficient to induce platelet aggregation, increased binding to collagen and thrombus formation was observed. Using antagonists specific to protease-activated receptors 1 and 4, we demonstrate their role in mediating staphopain A induced platelet activation.

Characteristics and outcomes in patients with infective endocarditis caused by Enterococcus faecium and Enterococcus faecalis

Abstract Background Enterococcus faecalis is the third most common cause of infective endocarditis (IE) and has been associated with a higher risk of relapse and death. Within the enterococcus species, E. faecium is the second most frequent cause of IE. As IE from E. faecalis or E. faecium most likely have different presentations and outcomes, research is needed for individualised and optimised clinical management. Purpose This study aims to characterise baseline characteristics and clinical outcomes for patients with IE caused by E. faecalis or E. faecium, including short- and long-term mortality and relapse. Additionally, we aim to determine risk factors associated with IE caused by the two bacterial species. Methods This is a retrospective study of patients hospitalised with at least one positive blood culture with E. faecalis or E. faecium between January 1, 2016 and December 31, 2018 at two large hospitals in Denmark. IE was diagnosed according to the modified Duke criteria. Index and follow-up data were collected from medical records. Categorical values were compared using chi-square test and categorial data using students t-test. Results 614 patients had a positive blood culture with either E. faecalis (n=279) or E. faecium (n=335). Of these, 64 (10.4%) patients developed IE; E. faecalis in 56 patients (87.5%, male 83.3%, mean age 70 years (SD 14)) and E. faecium in 8 patients (12.5%, male 75.0%, mean age 65 years (SD 13)). The prevalence of IE was 20.1% for E. faecalis bacteraemia and 2.4% for E. faecium bacteraemia (p<0.001). Embolic events during primary admission were seen more often in the E. faecium group (62.5%) compared to the E. faecalis group (10.7%) (p=0.002). Both groups had multiple co-morbidities without significant differences between groups (Table 1). Nineteen (40.4%) of the patients with E. faecalis IE had a minimum of one previous admission with E. faecalis bacteraemia within the last year before the IE diagnosis, whereas this was not seen for any patients with E. faecium IE. The 30-days all-cause mortality was 5.4% for patients with E. faecalis IE and 25% for patients with E. faecium IE (p=0.22). After a median follow up of 3.1 years (IQR=0.46–3.94) all-cause mortality was 55.4% for patients with E. faecalis IE and 62.5% for patients with E. faecium IE (p=1.00) (Table 1). Conclusion The prevalence of IE was significantly higher in patients with E. faecalis bacteraemia than with E. faecium bacteraemia. While the prevalence of complications was higher in patients with E. faecium IE, the difference was only significant for embolic events. This indicates that E. faecium IE is associated with a worse outcome compared to the outcome in patients with E. faecalis IE. All-cause mortality was above 50% for both groups, i.e. considerably higher than generally seen in patients with IE. These findings may be of importance of management of patients with E. faecalis or with E. faecium bacteraemia – and endocarditis. Funding Acknowledgement Type of funding sources: None.

PROSTHETIC VALVE INFECTIVE ENDOCARDITIS CAUSED BY SERRATIA MARCESCENS IN A PATIENT WITH SURGICAL WOUND INFECTION

PROSTHETIC VALVE INFECTIVE ENDOCARDITIS CAUSED BY SERRATIA MARCESCENS IN A PATIENT WITH SURGICAL WOUND INFECTION

AN UNUSUAL CASE OF SUBACUTE BACTERIAL ENDOCARDITIS PRESENTING WITH CATASTROPHIC SUBARACHNOID HEMORRHAGE

AN UNUSUAL CASE OF SUBACUTE BACTERIAL ENDOCARDITIS PRESENTING WITH CATASTROPHIC SUBARACHNOID HEMORRHAGE

Temporal Changes, Patient Characteristics, and Mortality, According to Microbiological Cause of Infective Endocarditis: ANationwide Study.

BackgroundMonitoring of microbiological cause of infective endocarditis (IE) remains key in the understanding of IE; however, data from large, unselected cohorts are sparse. We aimed to examine temporal changes, patient characteristics, and in‐hospital and long‐term mortality, according to microbiological cause in patients with IE from 2010 to 2017.Methods and ResultsLinking Danish nationwide registries, we identified all patients with first‐time IE. In‐hospital and long‐term mortality rates were assessed according to microbiological cause and compared using multivariable adjusted logistic regression analysis and Cox proportional hazard analysis, respectively. A total of 4123 patients were included. Staphylococcus aureus was the most frequent cause (28.1%), followed by Streptococcus species (26.0%), Enterococcus species (15.5%), coagulase‐negative staphylococci (6.2%), and “other microbiological causes” (5.3%). Blood culture–negative IE was registered in 18.9%. The proportion of blood culture–negative IE declined during the study period, whereas no significant changes were seen for any microbiological cause. Patients with Enterococcus species were older and more often had a prosthetic heart valve compared with other causes. For Streptococcus species IE, in‐hospital and long‐term mortality (median follow‐up, 2.3 years) were 11.1% and 58.5%, respectively. Compared with Streptococcus species IE, the following causes were associated with a higher in‐hospital mortality: S aureus IE (odds ratio [OR], 3.48 [95% CI, 2.74–4.42]), Enterococcus species IE (OR, 1.48 [95% CI, 1.11–1.97]), coagulase‐negative staphylococci IE (OR, 1.79 [95% CI, 1.21–2.65]), “other microbiological cause” (OR, 1.47 [95% CI, 0.95–2.27]), and blood culture–negative IE (OR, 1.99 [95% CI, 1.52–2.61]); and the following causes were associated with higher mortality following discharge (median follow‐up, 2.9 years): S aureus IE (hazard ratio [HR], 1.39 [95% CI, 1.19–1.62]), Enterococcus species IE (HR, 1.31 [95% CI, 1.11–1.54]), coagulase‐negative staphylococci IE (HR, 1.07 [95% CI, 0.85–1.36]), “other microbiological cause” (HR, 1.45 [95% CI, 1.13–1.85]), and blood culture–negative IE (HR, 1.05 [95% CI, 0.89–1.25]).ConclusionsThis nationwide study showed that S aureus was the most frequent microbiological cause of IE, followed by Streptococcus species and Enterococcus species. Patients with S aureus IE had the highest in‐hospital mortality.

Staphylococcus aureus increases platelet reactivity in patients with infective endocarditis

Thromboembolism is frequent in infective endocarditis (IE). However, the optimal antithrombotic regimen in IE is unknown. Staphylococcus aureus (SA) is the leading cause of IE. First studies emphasize increased platelet reactivity by SA. In this pilot study, we hypothesized that platelet reactivity is increased in patients with SA− IE, which could be abrogated by antiplatelet medication. We conducted a prospective, observatory, single-center cohort study in 114 patients with IE, with four cohorts: (1) SA coagulase positive IE without aspirin (ASA) medication, (2) coagulase negative IE without ASA, (3) SA coagulase positive IE with ASA, (4) coagulase negative IE with ASA. Platelet function was measured by Multiplate electrode aggregometry, blood clotting by ROTEM thromboelastometry. Bleeding events were assessed according to TIMI classification. In ASA-naïve patients, aggregation with ADP was increased with coag. pos. IE (coagulase negative: 39.47 ± 4.13 AUC vs. coagulase positive: 59.46 ± 8.19 AUC, p = 0.0219). This was abrogated with ASA medication (coagulase negative: 42.4 ± 4.67 AUC vs. coagulase positive: 45.11 ± 6.063 AUC p = 0.7824). Aspirin did not increase bleeding in SA positive patients. However, in SA negative patients with aspirin, red blood cell transfusions were enhanced. SA coagulase positive IE is associated with increased platelet reactivity. This could be abrogated by aspirin without increased bleeding risk. The results of this pilot study suggest that ASA might be beneficial in SA coagulase positive IE. This needs to be confirmed in clinical trials.

Bacteraemia and infective endocarditis with Streptococcus bovis-Streptococcus equinus-complex: a retrospective cohort study

Background Streptococcus bovis/equinus complex (SBSEC) comprise several species and subspecies and is a common cause of infective endocarditis (IE). S. gallolyticus subsp. gallolyticus (Sg gallolyticus) accounts for a majority of SBSEC IE, but the risk of IE for other subspecies is largely unknown. We aimed to investigate the clinical presentation of bacteraemia, and proportion of patients with IE in bacteraemia with the most common subspecies. Methods A retrospective cohort study of SBSEC-bacteraemia identified in clinical laboratory databases, in Skåne Region, Sweden, 2003–2018. Bacteraemia with Sg gallolyticus, S. gallolyticus subsp. pasteurianus (Sg pasteurianus), S. lutetiensis and S. infantarius subsp. infantarius (Si infantarius) were included. Subspecies was identified by whole genome sequencing. Medical charts were reviewed according to a predetermined protocol, IE was defined by the criteria from European Society of Cardiology. Results In total, 210 episodes of SBSEC-bacteraemia were included. Definite IE was identified in 28/210 (13%) episodes. Of these, 7/28 (25%) were prosthetic valve-IE, 1/28 (4%) related to a cardiovascular implantable electronic device and 10/28 (36%) required heart valve surgery. The proportions of IE among different subspecies were: Sg gallolyticus 17/52 (33%), Si infantarius 5/31 (16%), Sg pasteurianus 4/83 (5%) and S. lutetiensis 2/44 (5%) (p < 0.001). Sg pasteurianus and S. lutetiensis were more often associated with intra-abdominal- and polymicrobial infection. Conclusion The proportion of IE in SBSEC-bacteraemia varies substantially depending on subspecies. Echocardiography should always be considered in bacteraemia with Sg gallolyticus and Si infantarius, and can sometimes be omitted in bacteraemia with Sg pasteurianus and S. lutetiensis.

Dalbavancin as an option for treatment of S. aureus bacteremia (DOTS): study protocol for a phase 2b, multicenter, randomized, open-label clinical trial

BackgroundStaphylococcus aureus bacteremia is a life-threatening infection and leading cause of infective endocarditis, with mortality rates of 15–50%. Treatment typically requires prolonged administration of parenteral therapy, itself associated with high costs and potential catheter-associated complications. Dalbavancin is a lipoglycopeptide with potent activity against Staphylococcus and a long half-life, making it an appealing potential therapy for S. aureus bacteremia without the need for durable central venous access.MethodsDOTS is a phase 2b, multicenter, randomized, assessor-blinded, superiority, active-controlled, parallel-group trial. The trial will enroll 200 adults diagnosed with complicated S. aureus bacteremia, including definite or possible right-sided infective endocarditis, who have been treated with effective antibiotic therapy for at least 72 h (maximum 10 days) and with subsequent clearance of bacteremia prior to randomization to study treatment. Subjects will be randomized 1:1 to complete their antibiotic treatment course with either two doses of dalbavancin on days 1 and 8, or with a total of 4–8 weeks of standard intravenous antibiotic therapy. The primary objective is to compare the Desirability of Outcome Ranking (DOOR) at day 70 for patients randomized to dalbavancin versus standard of care. Key secondary endpoints include quality of life outcomes and pharmacokinetic analyses of dalbavancin.DiscussionThe DOTS trial will establish whether dalbavancin is superior to standard parenteral antibiotic therapy for the completion of treatment of complicated S. aureus bacteremia.Trial registrationUS National Institutes of Health ClinicalTrials.govNCT04775953. Registered on 1 March 2021