Staphylococcus aureus is the leading cause of infective endocarditis in the United States. Infective endocarditis (IE) is defined as an infection of the endocardium, typically involving the heart valves. The hallmark features of IE are vegetations. Vegetations are cauliflower-like, stratified biofilms of bacteria and host factors that develop on the valve leaflets of the heart. The mechanisms of how vegetations form are not well understood, and as a consequence the bacterial factors that are important for development of IE are not well defined. My studies focus on the role of a family of S. aureus exoproteins known as superantigens and their role in IE. Superantigens (SAgs) are a class of secreted virulence factors that have been extensively studied for their role in systemic diseases such as toxic shock syndrome (TSS), pneumonia, and food poisoning. The SAg protein family is comprised of 23 distinct members designated as staphylococcal enterotoxin (SE) or enterotoxin-like (SEl) and toxic shock syndrome toxin-1 (TSST-1). The term superantigen is derived from the ability of SAgs to interact with the immune system, resulting in a nearly 3000-fold increase in activation when compared to standard antigens. SAgs have a defined structure that is composed of 2 domains, a carboxy-terminal beta-grasp domain and amino-terminal oligosaccharide/oligonucleotide binding (OB) fold. Defined groups of SAgs are associated with S. aureus strains isolated from specific diseases, but few studies have been done to determine the role of SAgs in diseases outside of TSS and food poisoning. The enterotoxin gene cluster (egc) is a group of 6 SAgs (selo, selm, sei, selu, seln, and seg) assembled into an operon-like cluster that is present in the majority of S. aureus strains isolated from IE patients. My studies have determined that the egc is able to induce vegetations when expressed in avirulent S. aureus strains. This is the first time the egc has been directly associated with IE. I further characterized the capacity of the individual egc proteins to induce vegetations. Four (selo, selm, sei, and selu) of the 6 egc SAgs were able to induce vegetation formation. This is the first time the individual egc proteins have been characterized and directly associated with IE. I also demonstrated that the egc proteins may not be exclusively expressed as a single polycistronic transcript but that selu and seg contain promoter elements that may drive their individual expression. Lastly, I provide evidence that the egc SAgs may be regulated by MgrA, a global regulator of S. aureus associated with virulence factor expression.

Staphylococcus aureus causes significant illnesses throughout the world, including toxic shock syndrome (TSS), pneumonia, and infective endocarditis. Major contributors to S. aureus illnesses are secreted virulence factors it produces, including superantigens and cytolysins. Rabbit cardiac physiology is considered similar to humans, and rabbits exhibit susceptibility to S. aureus superantigens and cytolysins. As such, rabbits are an excellent model for studying pneumonia, infective endocarditis, and sepsis, We examined the ability of USA200, USA300 and USA400 strains to cause vegetations and lethal sepsis in rabbits. USA200, TSST-1+ strains that produce only low amounts of Α-toxin, exhibited modest LD50 in sepsis (1x108-5x108) colony-forming units (CFUs), and 3/4 caused significant IE. USA200 strain MNPE, which produces high levels of Α-toxin, was both highly lethal (LD50 5x106 CFUs) and effective in causing IE. In contrast, USA300 strains were highly effective in causing lethal sepsis (LD50s 1 x 106 and 5 x 107 CFUs) but were minimally capable of causing IE. USA400 strains were both highly lethal (LD50s of 1 x 107 and 5 x 107 CFUs) and highly effective causes of IE. Additional studies investigated the role of phenol soluble modulins in infection. We showed that PSMs are important for the ability of S. aureus to cause sepsis but not infective endocarditis. Additionally, immunization against PSMs did not protect rabbits from lethal infection. Our studies show that clonal groups of S. aureus differ in abilities to cause infective endocarditis and lethal sepsis and suggest that secreted virulence factors, including superantigens and cytolysins, account for some of these differences. This thesis also investigates the use of superantigens and cytolysins as staphylococcal vaccine candidates. We generated three TSST-1 mutants; G31S/S32P, H135A, and Q136A. All rabbits administered these TSST-1 toxoids generated strong antibody responses (titers>10,000) that neutralized native TSST-1 in TSS models, both in vitro and in vivo. These TSST-1 mutants lacked detectable residual toxicity. Additionally, the TSST-1 mutants exhibited intrinsic adjuvant activity, increasing antibody responses to a second staphylococcal antigen (Β-toxin). This effect may be due to TSST-1 mutants binding to the immune co-stimulatory molecule CD40. The superantigens TSST-1 and SEC and the cytolysin Α-toxin are known to contribute to staphylococcal pneumonia. Immunization of rabbits against these secreted toxins provided complete protection from highly lethal challenge with a USA200 S. aureus strain producing all three exotoxins; USA200 strains are common causes of staphylococcal infections. The same three exotoxins plus the cytolysins Β-toxin and Γ-toxin contribute to infective endocarditis and sepsis caused by USA200 strains. Immunization against these five exotoxins protected rabbits from infective endocarditis and lethal sepsis. Additionally, a heptavalent vaccine composed of the pentavalent units plus SEB and SE-l X protected rabbits from lethal pneumonia caused by USA100 strain 209. Passive immunization using pooled sera protects previously non-immunized rabbits from lethal pneumonia due to MNPE. These data suggest that immunization against toxoid proteins of S. aureus exotoxins protects from serious illnesses, and concurrently superantigen toxoid mutants provide endogenous adjuvant activity.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 4 uppsatser.

Objective: Following the incidental multicenter study of Endocarditis 2007 check the quality of microbiological diagnosis of infective endocarditis (IE) in the Czech Republic. Material and Methods: Prospective multicenter study of Endocarditis 2007 examined the incidence and characteristics of infective endocarditis for 12 months (February 1, 2007 to January 31, 2008) in 29 hospitals in the country. Mandates doctors sent to the Prague Centre report all cases of IE in a pre-defined catchment area of their hospitals. Was used for reporting standard form, data about patients were anonymous. There were collected 132 reports of IE. My own work consisted in re-processing and verification of data on etiology and diagnosis of IE. The basis of retrospective telephone inquiries were directed to the appropriate microbiological department, with particular emphasis on the actual number of blood cultures for individual patients, and culture findings. After comparing data with data received reports from microbiology laboratories was corrected any incorrect information. So the results were validated by the study. At the same time to assess the quality of the interpretation of microbiological findings of clinicians. Conclusion: Previous use of antibiotics reduces the probability of detection of pathogens. This relationship...

Evalúa la técnica de Electrocauterio como alternativa para tratamiento de pulpotomía y sus beneficios. La atención de tratamiento integral en sala de operaciones en paciente de 6 años del Servicio de Cardiología del INSN, con Diagnostico de Endocarditis bacteriana, se realizó dos pulpotomias en dientes deciduos con electrocauterio, se colocó base Oxido de Zinc + Eugenol, luego se colocó Ionómero de vidrio y resina fotocurable con técnica incremental. La respuesta de las piezas tratadas con Electrocauterio fue favorable clínica y radiográficamente. Se concluye que al considerar al Electrocauterio como tratamiento no farmacológico alternativo. / Trabajo académico

With the advent of more effective therapies for human immunodeficiency virus (HIV) infection, HIV-infected patients are living longer and cardiovascular disease is becoming more obvious in this population. Patients with HIV infection represent one of the most rapidly developing groups with cardiovascular disease globally. Cardiovascular disease complicating HIV infection is likely to contribute to burgeoning healthcare costs. Pericarditis, myocarditis, cardiomyopathy, atherosclerotic coronary vasculopathy, arterial aneurysms, pulmonary hypertension, and endocarditis occur with increased frequency in these patients. Pedcardial tamponade, dilated cardiomyopathy, endocarditis, and vasculopathy can lead to fatal outcomes in this population. The advent of cardiomyopathy heralds a very poor prognosis in patients infected with HIV. Coronary vasculopathy without obvious risk factors can lead to myocardial ischemia in young patients infected with the virus. MoreoVer, the protease inhibitors used to treat HIV infection induce a syndrome of lipodystrophy and dyslipidemia that may be associated with accelerated atherosclerosis as well as insulin resistance. All these factors contribute to increased cardiovascular morbidity and mortality in the HIV-infected population. HIV infection, opportunistic infections, secreted viral proteins such as gp120 (envelope protein) or Tat (transactivator of viral transcription), and cytokines elaborated during the course of HIV infection of the immune system all contribute to pathogenesis of these disorders. Further basic and clinical studies are required to understand the pathogenesis of cardiovascular complications and develop appropriate management strategies for these patients.

Vancomycin has been considered first-line treatment for bacteremia caused by methicillin-resistant Staphylococcus aureus (MRSA) despite treatment failures in up to 20% of patients with MRSA bacteremia secondary to endocarditis. However, trimethoprim-sulfamethoxazole (TMP-SMX) is as effective as vancomycin for the management of MRSA bacteremia. secondary to endocarditis in injection drug users. We report the successful management of a left ventricular assist device-related MRSA infection with persistent MRSA bacteremia that failed to respond to vancomycin, linezolid, and quinupristin/dalfopristin but did respond to TMP-SMX.

Aortic dissection is a life-threatening emergency associated with significant mortality rate. Early diagnosis is essential to improve the survival. Although the most common presentation is severe chest pain, it can be variable leading to delay in the diagnosis especially if it is painless. Painless aortic dissection is a rare entity with sparse data available based on case reports. We present a case of a young male with an atypical presentation where the presumptive diagnosis of infective endocarditis was made based on initial presentation but was eventually diagnosed as painless aortic dissection.

In the setting of an increasing incidence of endocarditis in the United States, we report a patient with necrotizing crescentic glomerulonephritis (GN) associated with native valve bacterial endocarditis due to Streptococcus parasanguinis. He was started on appropriate antibiotic treatment and subsequent blood cultures showed no growth. However, due to continuing decline in kidney function, immunosuppressive therapy was started. Despite immunosuppressive therapy and antibiotics, renal function did not improve and chronic hemodialysis was required. Due to rarity of condition, there are no definite treatment guidelines available. Antibiotics, steroids, immunosuppressive agents can be of help in most cases. Further research in this regard may help with early diagnosis and better treatment modalities.

complex has been further divided into , , and . is considered to be the least virulent fungi of the complex. Candida endocarditis is uncommon but is associated with a very high mortality rate. Prosthetic or previously damaged valves act as common targets, but native, structurally normal valves are seldom affected. We hereby present a case of endocarditis involving a native aortic valve in an immunocompetent 55-year-old male who was successfully treated with surgical valve replacement and antifungal therapy.