BACKGROUND: Treatment of left-sided Infective Endocarditis (IE) is challenging due to the presence of both surgical and medical interventions. The choice typically depends on the patient’s surgical risk and severity of infection. Our aim is to compare outcomes of IE patients who undergo valve replacement surgery with patients who are treated with solely antibiotics. METHODS: Patients undergoing valve surgery at our institution from 1995 to 2014 (n=196) and patients who were treated medically for IE from 2001 to 2014 (n=120) were included in this study. In total, 316 patients were included and clinical data was retrospectively collected from chart review. Society of Thoracic Surgeons (STS) Scores were calculated to assess for surgical risk and data for preoperative fever, angina, and abscess was collected to assess for severity of infection. The primary outcome of interest was mortality at 30 days and 1 year post-treatment and secondary outcomes included post-treatment development of septic shock, MI, embolic events, recurrence of infection, stroke, and renal dysfunction. Cox regression analyses were performed to assess the likelihood of mortality based on the patient’s pre-intervention comorbidities and characteristics. A Kaplan-Meier Analysis was also conducted to assess for survival at both 30 days and 1 year. RESULTS: Pre-operative fever (68.88% surgical vs 52.50% medical, p=0.002), angina (13.78% surgical vs 2.50% medical, p<0.05), and presence of abscess (33.37% surgical vs 6.67% medical, p<0.05) were significantly higher in the surgical population. Mortality at both 30-days (7.65% surgical vs 29.17% medical, p<0.05) and 1 year (17.35% surgical vs 46.67% medical, p<0.05) was significantly higher in the medical cohort. Mortality in patients presenting with valvular abscess was significantly higher in the surgical population at 30 days (4.5% surgical vs 62.5% medical, p<0.05) and 1 year (15.15% surgical vs. 75.00% medical, p<0.05). Surgical risk was significantly higher in medical patients overall (p<0.05), but not significantly higher in the pathogen specific subgroups. By individual pathogen, medical mortality was significantly higher at both 30 days and 1 year in the MRSA (p=0.0004 and p=0.0002) and Staphylococcus population (p=0.001 and p=0.0005) but only significantly higher in the Streptococcus population at 1 year (p=0.032). CONCLUSION: Valve Replacement Surgery in patients with left-sided MRSA and non-MRSA Staphylococcus IE leads to significantly better mortality outcomes at 30 days and 1 year than medical management. Specifically, we suggest that patients with preoperative valvular abscess undergo valve replacement surgery, regardless of pathogen, and that patients with MRSA and non-MRSA Staphylococcus IE be strongly considered for surgical intervention.

published_or_final_version / Medicine / Master / Master of Medical Sciences

Thesis (M.Med.Sc.)--University of Hong Kong, 2009. / Includes bibliographical references (p. 81-91).

Purpose: The aim was to determine the echocardiographic features of patients with infective endocarditis, and to compare the findings in HIV positive versus HIV negative patients. Methods: This was a prospective study, conducted over three years using the modified Duke criteria in diagnoses. A control group of age-matched patients with clinical and echocardiographic evidence of valvular regurgitation, who did not satisfy the criteria and who underwent surgery was used in comparison. Results: During this period 91 patients were screened for infective endocarditis. 77 satisfied the criteria for a definite diagnosis of IE. Blood cultures were positive in 46% cases. The commonest organism was S. aureus. Most patients had advanced valve disruption with heart failure and a high peri-operative mortality. The clinical features in the two groups of patients was similar. The incidence of echocardiographic complications was 50.6% in the whole group. Except for leaflet aneurysms in four HIV positive cases, complications were not more frequent in this group. Conclusion: There was a high rate of culture negative cases in this study, probably related to prior antibiotic usage; in this setting the modified Duke criteria have diagnostic limitations. There was no difference in the clinical presentation of infective endocarditis between HIV positive and HIV negative patients. Leaflet aneurysms were more common in the HIV positive patients. / Thesis (M.Med.)-University of KwaZulu-Natal, 2008.

Thesis (Ph. D.)--University of Sydney, 2005. / Title from title screen (viewed 21 May 2008). Submitted in fulfilment of the requirements for the degree of Doctor of Philosophy to the Discipline of Oral Biology, Faculty of Dentistry. Includes bibliographical references. Also available in print form.

Infective endocarditis due to Bartonella bacilliformis is rare. A 64-year-old woman, without previous heart disease, presented with 6 weeks of fever, myalgias, and arthralgias. A systolic murmur was heard on the tricuspid area upon examination, and an echocardiogram showed endocardial lesions in the right atrium. Bartonella bacilliformis was isolated in blood cultures, defining the diagnosis of infective endocarditis using Duke’s criteria. Subsequently, the patient developed clinical and laboratory features compatible with antineutrophil cytoplasmic antibody-associated vasculitis. This case presents an uncommon complication of B. bacilliformis infection associated with the development of systemic vasculitis.

Introduction: Advances in modern medicine have enabled early detection of infective diagnosis through blood cultures and echocardiography, which have been standardized by the widely accepted Modified Duke Criteria and have enabled rapid administration of antibiotics. As a consequence, the well-discussed and often variable clinical findings have become less common and have relegated to minor criteria in diagnosis. Fever is the single most common presenting symptom, whereas more specific signs such as petechiae may be seen in only 20-40% of patients. Even more rare are the pathognomonic Janeway lesions, Roth spots, and Osler nodes. Here we present a case in which early diagnosis was established through minor criteria manifest upon physical exam, and we highlight the timely insight provided from physical exam. Case: A 29-year-old man was admitted to the hospital for altered mental status, fever, vomiting, diarrhea, and vertigo. His past medical history included IV drug abuse, thrombotic thrombocytopenia, Hepatitis C, and seizures. Upon admission, his encephalopathy progressed rapidly, and he was mechanically ventilated and started on hemodialysis. Blood cultures grew Methicillin sensitive Staphylococcus aureus and Elizabethkingia meningosepticum and susceptibilities were attained. Echocardiography showed 3.1 cm vegetation on the aortic valve. By the Modified Duke Criteria, the diagnosis of infective endocarditis was confirmed. Discussion: The increasing incidence of complex infective endocarditis—including polymicrobial infection as well as the increasing resistance to antibiotic therapy—poses challenges to the rapid assessment and treatment necessary to mitigate the multi-organ involvement and the devastating consequences of septic emboli. Developments in medical technology have expedited both the diagnosis and treatment of infective endocarditis, which has subsequently decreased the extent and frequency of classical signs. Nonetheless, this case illustrates the unavoidable vitality of the physical exam, because this patient’s quick and clear presentation enabled diagnosis solely through physical exam. Empiric antibiotic treatment was started promptly and subsequently adjusted based on culture and susceptibilities.

Submitted in partial fulfillment of the requirements for the degree of Master of Technology (Clinical Technology : Cardiology), Department of Clinical Technology, Durban University of Technology, Durban, South Africa, 2015. / Introduction Infective endocarditis is a serious disease that needs rapid diagnosis and accurate risk stratification to offer the best therapeutic strategy. Echocardiography plays a key role in the management of the disease but may be limited in some clinical situations. Moreover, this method is insensitive for very early detection of the infection and assessment of therapeutic response because it does not provide imaging at the molecular and cellular levels. Recently, several novel morphological, molecular and hybrid imaging modalities have been investigated in infective endocarditis and offer new perspectives for better management of the disease. Aims and Objectives of the Study This prospective, quantitative and observational study was investigated at Dr George Mukhari Hospital in Pretoria, South Africa. Infective Endocarditis is a serious disease associated with poor prognosis despite improvements in medical and surgical therapies. Infective Endocarditis results in complex pathogenesis that involves many host-pathogen interactions. Indeed, previous endocardial lesions can lead to the exposure of the underlying extracellular matrix proteins, local inflammation and then thrombus formation, which is termed ‘non-bacterial vegetation’. The project aims to compare the echocardiographic findings (transthoracic echocardiographic-TTE) with intraoperative findings on patients with infective endocarditis. If the correlation existed then the echocardiogram findings were accurate when performed in patients with infective endocarditis. Methodology The research participants consisted of forty (40) patients with infective endocarditis at Dr George Mukhari Hospital in Pretoria, South Africa. A cardiologist examined the patient’s clinically for features of infective endocarditis. Two techniques were used to assess the infective endocarditis. These included echocardiography and Intraoperative findings (visual and histology). Bloods were cultured to demonstrate the presence of micro-organisms. Blood was sent to the laboratory for culture in order to detect the presence of micro-organisms. The researcher performed an Echocardiogram to assess which valve was affected, the left ventricular endiastolic diameter (LVED), the left ventricular ensystolic diameter (LVES), the shortening fraction (SF), the ejection fraction (EF) and the size of the vegetation/mass or abscess. For patients requiring a heart surgery, the cardiac surgeon performed the valve replacement, and the intra-operative findings was assessed visually to confirm the presence of vegetation or abscess and leaflets destruction. During the operation, which was performed by the same cardiac surgeon, a biopsy sample was taken for histological examination to confirm the presence of vegetation or abscess. Thereafter, the cardiac surgeon performed the valve repair/ replacement/ bioprosthesis. The researcher was blinded to the findings in the theatre as the researcher was not present in the theatre. The results from the laboratory was sent to the researcher. The researcher was then able to confirm the presence of vegetation or mass/ abscess and leaf destruction. Results The histology confirmed what was seen on echocardiographical findings and intraoperative findings (visual). The intraoperative and echocardiography findings showed thirty two of 40 (80%) vegetation, two of 40 (5%) perforation, four of 40 (10%) pseudoaneursym and two of 40 (5%) abscesses. The prognosis of patients with poor ejection fraction (40-50% EF) was poorer than those with good ejection fraction (60-75%). The clinical findings of all patients confirmed infective endocarditis and thirty two of 40 (80%) blood cultures were positive and eight of 40 (20%) were negative. There were seven of 40 (17,5%) patients who showed poor correlation 40- 50% between echocardiographical findings and post-operative findings. The results of thirty three of 40 (82%) patients showed moderate correlation 69% between the echocardiographical findings and post-operative findings. Conclusion My findings of the study was that eight of 40 (20%) had stenosis and thirty two of 40 (80%) had regurgitation in patients who had infective endocarditis. There was an overall moderate association (r=0.68) between echocardiography and the intraoperative findings in all patients for LVES.

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.

Thesis (M.S.)--University of Michigan, 1976.