Reduction of the susceptibility to infective endocarditis with time in animals with endocavitary catheters.

In a previous study we showed that the lesions of non-bacterial thrombotic endocarditis induced by means of implantation of a catheter in the left ventricle (LV) of the rabbit, undergo inner connectivization and surface endothelialization, which are completed within 2-3 months. In the present study we have investigated whether these histological changes lead to a variation in susceptibility to infective endocarditis (IE). After studying two control groups, we compared the incidence of IE in four groups of 15 rabbits each, inoculated with Streptococcus mitis I, 10, 35 and 70 days after implantation of a catheter in the LV. The frequency of infection was shown to be progressively reduced from 100% to 26.7%. This demonstrates that endothelialization of the catheter and the sterile vegetations protect the animals from IE.     

Aminoglycosides for infective endocarditis: time to say goodbye?

BackgroundBased on experimental studies showing synergism with β-lactams and glycopeptides, aminoglycosides have long been considered essential in the treatment of infective endocarditis (IE). However, their use is associated with a high risk of renal failure, especially in elderly patients.AimsThe aim of this narrative review was to summarize the evidence to support reducing or even avoiding the use of aminoglycosides for the treatment of IE. We also analysed data supporting the use of aminoglycosides in specific subgroup of IE patients.SourcesPubMed database was searched up to July 2019 to identify relevant studies.ContentsRecent European Guidelines reduced the use of aminoglycosides in IE, no longer recommended in Staphylococcus aureus native-valve IE, and shortened to 2 weeks for IE related to Enterococcus faecalis and streptococci with penicillin MIC >0.125 μg/mL. In addition, an alternative regimen without aminoglycosides (ampicillin or amoxicillin plus ceftriaxone) is proposed for E. faecalis. Observational studies suggested that gentamicin would not be necessary in the case of staphylococcal prosthetic valve IE as long as rifampicin is maintained. Recent clinical studies showed that for streptococcal IE, gentamicin could be restricted to isolates with penicillin MIC >0.5 μg/mL. For the empirical and definitive treatment of E. faecalis IE, amoxicillin or ampicillin plus ceftriaxone may be considered, irrespective of high-level of aminoglycoside resistance.ImplicationsIn a scenario of progressive increase in the age and frailty of IE patients, the use of aminoglycosides can be reduced or avoided in ~90% cases. This should result in reduced incidence of renal failure, an important prognostic factor in IE.     

Pathogenesis of infective endocarditis

The present knowledge of epidemiology, microbiology and pathogenesis of infective endocarditis in both native valve and prosthetic valve endocarditis is described. An attempt has been made to discuss early events in its pathogenesis. This understanding may help in the prevention and management strategies.     

Autoreactive mechanisms in infective endocarditis

Summary Infective endocarditis is not a simple interaction between a microbial agent and a cardiac valve. For the infection of a non-bacterial thrombotic vegetation, predisposition is required which is at least partially operative by a decreased suppressor T cell activity. During infection, peripheral blood natural killer cell activity is decreased, but normalizes under anti-microbial therapy. Non-major histocompatibility complex-restricted lymphocytotoxicity to isolated heart cells can be present in one third of patients. Circulating immune complexes normalize during therapy. They may be the cause of many clinical symptoms of infective endocarditis. Anti-bacterial and also anti-sarcolemmal antibodies which are cross-reactive to the bacterium are secreted in a polyclonal immune response. Anti-sarcolemmal antibodies which are cytolytic in vitro in the presence of complement may partly explain the myocardial factor of heart failure in patients with only marginal valve incompetence due to the endocarditic vegetation.     

Evolving trends in infective endocarditis

Infective endocarditis is a microbial infection of the endocardial surface and, despite improvements in diagnostic accuracy, medical therapy and surgical techniques, mortality remains high. This review focuses on changes in epidemiology, microbiology and diagnosis, as well as changes in medical and surgical management of infective endocarditis affecting native and prosthetic valves in adults, that have evolved during the past two decades. Significant changes have included an increasing involvement of prosthetic valves and nosocomially-acquired disease, an increased involvement of staphylococci as the causative agents, and a recognition that elderly individuals with degenerative valvular disease are the most vulnerable population. Topics still requiring study include whether and when valve replacement should be performed, and how to predict perivalvular complications or embolisation based on echocardiography findings. Optimisation of antimicrobial treatment schemes (choice of the antibiotic, dose and duration) also requires further investigation.     

Role of surgery in infective endocarditis

One-hundred-and-thirteen patients with endocarditis and valvular insufficiency were studied retrospectively with special regard to indications for operation and the optimum time for cardiac valve surgery. Thirty patients (group I) had acute, 63 (group II) subacute and 20 (group III) prosthetic valve endocarditis. Group I: Eleven patients underwent surgery in the acute stage, 8 while bacteremic; 5 of the latter died perioperatively. Of the 19 patients treated medically, 16 died. Group II: All patients underwent operation in a bacteria-free state. The mortality was 5%. Group III: Eight patients had early (less than 60 days postoperatively) and 12 late endocarditis. Total mortality was 40% (71% early and 25% late mortality). Ten patients underwent reoperation, with a mortality of 20%, compared with 60% in the medically treated group. The results support the indication for early operation in acute endocarditis with progressive cardiac failure and renal failure and prosthetic valve endocarditis, even during bacteremia.     

Pathologic findings in native infective endocarditis

BackgroundThere are few studies on the histologic findings in native infective endocarditis, especially regarding mimics of autoimmune valvulitis.MethodsWe prospectively studied 106 surgical specimens from 95 patients with a clinical diagnosis of infective endocarditis on native valves, and compared gross and histologic findings with culture results, underlying valve disease, risk factors and time interval from symptom onset to surgical intervention.ResultsThere were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(.9%) pulmonic and 11 (10%) multiple valve replacements. Underlying valve disease was present in 26 (27%) patients (non-calcified bicuspid aortic valve, 10 (38%) cases; mitral valve prolapse, 5 (19%) cases; calcified trileaflet aortic valve, 5 (19%) cases; calcified bicuspid aortic valve, 2 (8%) cases; post-rheumatic mitral valve disease, 2 (8%) cases; hypertrophic cardiomyopathy-related mitral valve disease, 1 (4%) case, trileaflet aortic insufficiency 1 (4%) case) and associated with streptococcal infection (p = .001). Absence of underlying valve disease was associated with intravenous drug abuse (p = .01) and dialysis dependent renal disease (p = .006). Intravenous drug abuse was associated with staphylococcal infection (p = .03). Vegetations were present in 80 (75%) of cases, and on the nonflow surface of the valve in 65 (81%) of these. Gram-stain positivity and neutrophilic microabscesses were associated with staphylococcal infection (p = .03). Epithelioid macrophages with palisading features mimicking necrobiotic granulomas were seen in 42 (40%) valves and more frequently associated with streptococcal infection (p = .03). As expected, the presence of valve necrosis and acute inflammation decreased with an increase in time with respect to symptomatic onset.ConclusionHistologic findings that mimic autoimmune inflammation are frequent in infective endocarditis and associated with streptococcal infection. Risk factors for infective endocarditis include calcific valve disease.     

Antibiotic-resistant oral streptococci in dental patients susceptible to infective endocarditis

The aim of this study was to determine the incidence of amoxycillin and erythromycin resistance in oral streptococci in patients at risk from infective endocarditis. Samples of gingival crevicular flora were taken from 65 patients at the site of dental treatment, prior to the prophylactic administration of amoxycillin (54 patients) or erythromycin (11 patients). Samples were also taken from 65 dental patients who were not considered to be at risk from infective endocarditis. No isolate had a minimum inhibitory concentration (MIC) of amoxycillin greater than 24 mg/L. However, erythromycin-resistant oral streptococci with MIC values greater than 3.5 mg/L were isolated from 22% of patients receiving amoxycillin prophylaxis, 9% of patients receiving amoxycillin prophylaxis, 9% of patients given erythromycin prophylaxis and 9% of patients not at risk from infective endocarditis. The antibiotic-resistant streptococci comprised mainly Streptococcus sanguis biotype II, although S. sanguis biotype I, S. mitis and S. salivarius were also frequently recovered.     

Current trends in the molecular diagnosis of infective endocarditis

The introduction of molecular methods into biomedical science, particularly nucleic acid amplification techniques including the polymerase chain reaction, has significantly improved the diagnosis of several diseases. Likewise, the adoption of such molecular techniques to aid in the detection and identification of causal organisms in patients with infective endocarditis (IE) has been particularly beneficial in cases of difficult, atypical or culture-negative IE. Several different molecular approaches have been suggested for the diagnosis of IE, including variations in the type of cardiological specimens examined, nucleic acid extraction, gene target and molecular platform, each presenting their own advantages and disadvantages. This review examines the molecular approach to the detection and identification of causal agents of IE and provides details and a discussion of the application of such methods, particularly those implemented over the last 7 years.     

Antiphospholipid antibodies proposed in the diagnosis of infective endocarditis

Antiphospholipid antibodies (aPL) may occur alone or associated with other diseases. To evaluate aPL, tested as anticardiolipin antibodies (IgG aCL) in infective endocarditis (IE) diagnosis, we investigated their prevalence in a cohort of 651 patients with IE suspicion. aPL was significantly associated with definite IE versus IE-rejected patients. Their mean levels were significantly higher in patients with definite IE versus possible IE. When applied as Duke minor criterion, they were significantly more often positive, and at higher levels, in patients with definite IE than in patients with possible or rejected IE. aPL could be helpful in difficult cases of IE diagnosis.     

Update on pathogenesis of infective endocarditis

Specific interactions between pathogens and host factors contribute to the apparent tissue and microbial selectivity in infective endocarditis. Streptococci and staphylococci can produce exopolysaccharides and peptides that have been implicated in adherence to host factors. The presence of a platelet-fibrin matrix on the surface of endothelium can serve as a nidus for colonization by gram-positive cocci, which in turn can promote further aggregation of platelets. Tissue factor expression by valvular endothelial cells is low but can be turned on by endocytosis of staphylococci—this could favor infected thrombus formation. The presence of a foreign body such as a prosthetic heart valve increases the risk of endocarditis. Platelets can promote adherence of staphylococci to foreign body surfaces. Infection of heart valves is the result of influences that in the end will favor microbial attachment and survival. Normal endothelium is resistant to colonization by microorganisms. Antibodies and phagocytes offer some protection against the development of endocarditis. Platelets produce microbicidal proteins that appear important in containing the infection. New diagnostic criteria for endocarditis take into account the pathogenetic characteristics of the disease.     

Fatal hemopericardium due to ruptured solitary myocardial abscess unassociated with infective endocarditis

A case is presented of hemopericardium and sudden death due to rupture of a solitary myocardial abscess in an elderly woman with cirrhosis and mild urosepsis. If suspected clinically, such myocardial abscesses may be detectable by noninvasive tomographic cardiac imaging.