Treatment of enterococcal endocarditis requires up to 6 weeks of intravenous (IV) antimicrobial therapy. When susceptible, an ampicillin-based regimen is preferred. Studies evaluating ampicillin stability utilizing high-pressure liquid chromatography have indicated enhanced stability (greater than 24 hours at room temperature), supporting outpatient administration. Thus, we report the successful treatment of a 30-year-old male with tricuspid valve enterococcal endocarditis in an outpatient setting using continuous infusion ampicillin via an ambulatory infusion pump. The patient received daily gentamicin at an outpatient infusion center with the ampicillin dose to be infused over the next 24 hours. Outpatient ambulatory infusion pumps allow for delivery of ampicillin via continuous infusion or pump-programmed pulse dosing. Preparation and administration in an outpatient infusion center may be a viable option to circumvent stability and delivery issues. Furthermore, 81% (34/42) of treatment days were completed outpatient, supporting that this approach may increase access to treatment and help reduce the economic burden to health care.

Objectives: As surgical experience with infective endocarditis following transcatheter aortic valve replacement is scarce, this study compared the perioperative and short-term outcomes of patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement. Methods: Between January 2013 and December 2020, 468 consecutive patients were admitted to our center for surgery for IE. Among them, 98 were operated on for endocarditis following surgical aortic valve replacement and 22 for endocarditis following transcatheter aortic valve replacement. Results: The median EuroSCORE II (52.1 (40.6–62.0) v/s 45.4 (32.6–58.1), p = 0.207) and STS-PROM (1.8 (1.6–2.1) v/s 1.9 (1.4–2.2), p = 0.622) were comparable. Endocarditis following transcatheter aortic valve replacement accounted for 13.7% of the aortic prosthetic valve endocarditis between 2013 and 2015; this increased to 26.9% in the years 2019 and 2020.Concomitant procedures were performed in 35 patients (29.2%). The operative mortality was 26.5% in the endocarditis following surgical aortic valve replacement group and 9.1% in the endocarditis following transcatheter aortic valve replacement group (p = 0.098). Upon follow-up, survival at 6 months was found to be 98% in the group with endocarditis following surgical aortic valve replacement and 89% in the group with endocarditis following transcatheter aortic valve replacement (p = 0.081). Conclusions: Patients suffering from endocarditis following surgical aortic valve replacement and transcatheter aortic valve replacement present with comparable risk profiles and can be surgically treated with comparable results. Surgery as a curative option should not be rejected even in this intermediate-risk cohort

Endocardite infecciosa é uma doença associada à elevada morbidade e letalidade. O diagnóstico precoce e o reconhecimento de sua etiologia podem contribuir para o sucesso do tratamento antibiótico; entretanto, cerca de um quarto das endocardites permanece sem diagnóstico etiológico. Este estudo teve como objetivo principal identificar a frequência de endocardite por Bartonella spp. e Coxiella burnetii dentre as endocardites com culturas negativas comunitárias e avaliar os fatores preditores dessas infecções. Como objetivo secundário compararam-se as características clínicolaboratoriais e prognósticas entre as endocardites comunitárias com culturas negativas e positivas. Foram avaliados também os fatores associados à letalidade intra-hospitalar das endocardites com culturas negativas. Entre janeiro de 2004 e janeiro de 2009, foram investigados 369 episódios consecutivos de endocardite em pacientes atendidos no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - InCor HC-FMUSP. Foram estudados os casos que ocorreram em adultos, classificados pelos critérios de Duke modificados como \"endocardite definida\" e de origem comunitária. Assim, foram incluídos 221 episódios de endocardite, 170 com culturas positivas e 51 com culturas negativas. Neste último grupo, foram feitas as pesquisas sorológicas (reação de imunofluorescência indireta) e histopatológica de Bartonella spp. e Coxiella burnetii. Consideraram-se positivos títulos de imunoglobulina G (IgG) >= 800 para Bartonella henselae e ou Bartonella quintana, e IgG antifase I para C. burnetii > 800. O estudo histopatológico das valvas cardíacas foi capaz de identificar morfologicamente a etiologia de 87% das endocardites com culturas negativas, enquanto que o método de Gram do tecido a fresco o fez em somente 10% dos casos. As endocardites com culturas negativas apresentaram maior frequência de dispneia à admissão (p=0,001), menor valor de proteína C reativa (p=0,009), menor Fração de Ejeção do Ventrículo Esquerdo (Feve) (p=0,022) e necessitaram de mais tempo para o início do tratamento antibiótico para endocardite (p < 0,001) quando comparadas àquelas com culturas positivas. Não houve diferença estatisticamente significante entre os grupos na letalidade intra-hospitalar e na sobrevida após alta hospitalar. Verificou-se que a presença de diabetes mellitus (p=0,009) ou sepse grave na admissão (p=0,01) esteve independentemente associada ao óbito intra-hospitalar entre as endocardites com culturas negativas. Dez casos de endocardite por Bartonella spp. (frequência 19,6% [IC95%: 9,8 - 33,1]) e quatro casos de endocardite por Coxiella burnetii (frequência 7,8% [IC95%: 2,2 - 18,9]) foram diagnosticados dentre os 51 episódios de endocardite com culturas negativas. As endocardites por Bartonella spp. apresentavam menor Feve (p=0,025), associação com a identificação de cocobacilo Gram-negativo no exame histológico da valva cardíaca (p=0,001) e presença de gato no domicílio (p=0,001). Conclusões: Bartonella spp. e Coxiella burnetii foram as etiologias de quase um terço (27,5%) das endocardites comunitárias com culturas negativas. A presença de gato no domicílio, Feve <= 45%, e a identificação de cocobacilo Gramnegativo no exame histológico da valva cardíaca em pacientes com endocardite com culturas negativas parecem estar associadas à infecção por Bartonella spp. O exame histológico da valva cardíaca permitiu a identificação morfológica do micro-organismo na maioria dos casos, mesmo quando as hemoculturas estavam negativas. Não se observou diferença na letalidade intra-hospitalar e na sobrevida em longo prazo entre os dois grupos. A presença de diabetes mellitus ou sepse grave à admissão associou-se ao óbito hospitalar nas endocardites com culturas negativas / Infective endocarditis is associated with high morbidity and lethality. Early diagnosis and recognition of the specific etiology can contribute to successful antibiotic treatment. However, approximately one-fourth of endocarditis cases remain without an etiologic diagnosis. This study aimed to identify the frequency of endocarditis caused by Bartonella spp. and Coxiella burnetii among cases of community-acquired culture-negative endocarditis and to also assess risk factors for such infections. As a secondary objective, the clinical, laboratory and prognostic features of community-acquired endocarditis were compared. Factors related to the in-hospital lethality of culture-negative endocarditis were also assessed. Between January 2004 and January 2009, 369 consecutive cases of endocarditis were investigated in patients attending the no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - InCor HC-FMUSP. Cases occurring in adults, those classified by the modified Duke criteria as \"defined endocarditis\" and community-acquired cases were studied. In total, 221 cases of endocarditis comprising 170 culture-positive and 51 culturenegative cases were included. For the culture-negative cases, serology (indirect immunofluorescence reaction) and histopathological analyses for Bartonella spp. and Coxiella burnetii were performed. Cases were considered positive for Bartonella henselae or Bartonella quintana with IgG titers >= 800 and for Coxiella burnetii with antiphase I IgG titers > 800. Histopathological studies of the cardiac valves were capable of morphologically identifying the etiology in 87% of the culture-negative endocarditis cases, whereas the Gram stain was only positive in 10% of cases using fresh tissue. Culture-negative endocarditis patients presented a greater frequency of dyspnea on admission (p=0.001), lower C-reactive protein levels (p=0.009), and a lower left ventricular ejection fraction (LVEF) (p=0.022), and they required more time to start antibiotic therapy (p < 0.001) when compared with culture-positive patients. There was no statistically significant difference between the two groups regarding in-hospital lethality or survival after hospital discharge. Diabetes mellitus (p=0.01) or severe sepsis on admission (p=0.01) were independently associated with in-hospital death for culture-negative endocarditis. Ten cases of endocarditis caused by Bartonella spp. (frequency 19.6% [IC95%: 9.8 - 33.1]) and 4 caused by Coxiella burnetii (frequency 7.8% [IC95%: 2.2 - 18.9]) were diagnosed among the 51 cases of culture-negative endocarditis. Endocarditis caused by Bartonella spp. was associated with lower LVEF values (p=0.025), the identification of Gram-negative coccobacilli in cardiac valve histology (p=0.001) and the presence of a cat in the patient\'s residence (p=0.001). Conclusions: Bartonella spp. and Coxiella burnetii were the causative etiology of almost one-third (27.5%) of the community-acquired cases of culture-negative endocarditis. The presence of a cat in the patient\'s residence, a LVEF <= 45% and the identification of Gram-negative coccobacilli in the histological examination of the cardiac valve in patients with culturenegative endocarditis appear to be associated with Bartonella spp. as the causative etiology. Histological examination of the cardiac valves allowed for morphological identification of the causative microorganism in the majority of cases, even when blood cultures were negative. There was no difference in in-hospital lethality or long-term survival between the two groups. The presence of diabetes mellitus or severe sepsis at admission was associated with in-hospital death in cases of culture-negative endocarditis

Endocardite infecciosa é uma doença associada à elevada morbidade e letalidade. O diagnóstico precoce e o reconhecimento de sua etiologia podem contribuir para o sucesso do tratamento antibiótico; entretanto, cerca de um quarto das endocardites permanece sem diagnóstico etiológico. Este estudo teve como objetivo principal identificar a frequência de endocardite por Bartonella spp. e Coxiella burnetii dentre as endocardites com culturas negativas comunitárias e avaliar os fatores preditores dessas infecções. Como objetivo secundário compararam-se as características clínicolaboratoriais e prognósticas entre as endocardites comunitárias com culturas negativas e positivas. Foram avaliados também os fatores associados à letalidade intra-hospitalar das endocardites com culturas negativas. Entre janeiro de 2004 e janeiro de 2009, foram investigados 369 episódios consecutivos de endocardite em pacientes atendidos no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - InCor HC-FMUSP. Foram estudados os casos que ocorreram em adultos, classificados pelos critérios de Duke modificados como \"endocardite definida\" e de origem comunitária. Assim, foram incluídos 221 episódios de endocardite, 170 com culturas positivas e 51 com culturas negativas. Neste último grupo, foram feitas as pesquisas sorológicas (reação de imunofluorescência indireta) e histopatológica de Bartonella spp. e Coxiella burnetii. Consideraram-se positivos títulos de imunoglobulina G (IgG) >= 800 para Bartonella henselae e ou Bartonella quintana, e IgG antifase I para C. burnetii > 800. O estudo histopatológico das valvas cardíacas foi capaz de identificar morfologicamente a etiologia de 87% das endocardites com culturas negativas, enquanto que o método de Gram do tecido a fresco o fez em somente 10% dos casos. As endocardites com culturas negativas apresentaram maior frequência de dispneia à admissão (p=0,001), menor valor de proteína C reativa (p=0,009), menor Fração de Ejeção do Ventrículo Esquerdo (Feve) (p=0,022) e necessitaram de mais tempo para o início do tratamento antibiótico para endocardite (p < 0,001) quando comparadas àquelas com culturas positivas. Não houve diferença estatisticamente significante entre os grupos na letalidade intra-hospitalar e na sobrevida após alta hospitalar. Verificou-se que a presença de diabetes mellitus (p=0,009) ou sepse grave na admissão (p=0,01) esteve independentemente associada ao óbito intra-hospitalar entre as endocardites com culturas negativas. Dez casos de endocardite por Bartonella spp. (frequência 19,6% [IC95%: 9,8 - 33,1]) e quatro casos de endocardite por Coxiella burnetii (frequência 7,8% [IC95%: 2,2 - 18,9]) foram diagnosticados dentre os 51 episódios de endocardite com culturas negativas. As endocardites por Bartonella spp. apresentavam menor Feve (p=0,025), associação com a identificação de cocobacilo Gram-negativo no exame histológico da valva cardíaca (p=0,001) e presença de gato no domicílio (p=0,001). Conclusões: Bartonella spp. e Coxiella burnetii foram as etiologias de quase um terço (27,5%) das endocardites comunitárias com culturas negativas. A presença de gato no domicílio, Feve <= 45%, e a identificação de cocobacilo Gramnegativo no exame histológico da valva cardíaca em pacientes com endocardite com culturas negativas parecem estar associadas à infecção por Bartonella spp. O exame histológico da valva cardíaca permitiu a identificação morfológica do micro-organismo na maioria dos casos, mesmo quando as hemoculturas estavam negativas. Não se observou diferença na letalidade intra-hospitalar e na sobrevida em longo prazo entre os dois grupos. A presença de diabetes mellitus ou sepse grave à admissão associou-se ao óbito hospitalar nas endocardites com culturas negativas / Infective endocarditis is associated with high morbidity and lethality. Early diagnosis and recognition of the specific etiology can contribute to successful antibiotic treatment. However, approximately one-fourth of endocarditis cases remain without an etiologic diagnosis. This study aimed to identify the frequency of endocarditis caused by Bartonella spp. and Coxiella burnetii among cases of community-acquired culture-negative endocarditis and to also assess risk factors for such infections. As a secondary objective, the clinical, laboratory and prognostic features of community-acquired endocarditis were compared. Factors related to the in-hospital lethality of culture-negative endocarditis were also assessed. Between January 2004 and January 2009, 369 consecutive cases of endocarditis were investigated in patients attending the no Instituto do Coração do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo - InCor HC-FMUSP. Cases occurring in adults, those classified by the modified Duke criteria as \"defined endocarditis\" and community-acquired cases were studied. In total, 221 cases of endocarditis comprising 170 culture-positive and 51 culturenegative cases were included. For the culture-negative cases, serology (indirect immunofluorescence reaction) and histopathological analyses for Bartonella spp. and Coxiella burnetii were performed. Cases were considered positive for Bartonella henselae or Bartonella quintana with IgG titers >= 800 and for Coxiella burnetii with antiphase I IgG titers > 800. Histopathological studies of the cardiac valves were capable of morphologically identifying the etiology in 87% of the culture-negative endocarditis cases, whereas the Gram stain was only positive in 10% of cases using fresh tissue. Culture-negative endocarditis patients presented a greater frequency of dyspnea on admission (p=0.001), lower C-reactive protein levels (p=0.009), and a lower left ventricular ejection fraction (LVEF) (p=0.022), and they required more time to start antibiotic therapy (p < 0.001) when compared with culture-positive patients. There was no statistically significant difference between the two groups regarding in-hospital lethality or survival after hospital discharge. Diabetes mellitus (p=0.01) or severe sepsis on admission (p=0.01) were independently associated with in-hospital death for culture-negative endocarditis. Ten cases of endocarditis caused by Bartonella spp. (frequency 19.6% [IC95%: 9.8 - 33.1]) and 4 caused by Coxiella burnetii (frequency 7.8% [IC95%: 2.2 - 18.9]) were diagnosed among the 51 cases of culture-negative endocarditis. Endocarditis caused by Bartonella spp. was associated with lower LVEF values (p=0.025), the identification of Gram-negative coccobacilli in cardiac valve histology (p=0.001) and the presence of a cat in the patient\'s residence (p=0.001). Conclusions: Bartonella spp. and Coxiella burnetii were the causative etiology of almost one-third (27.5%) of the community-acquired cases of culture-negative endocarditis. The presence of a cat in the patient\'s residence, a LVEF <= 45% and the identification of Gram-negative coccobacilli in the histological examination of the cardiac valve in patients with culturenegative endocarditis appear to be associated with Bartonella spp. as the causative etiology. Histological examination of the cardiac valves allowed for morphological identification of the causative microorganism in the majority of cases, even when blood cultures were negative. There was no difference in in-hospital lethality or long-term survival between the two groups. The presence of diabetes mellitus or severe sepsis at admission was associated with in-hospital death in cases of culture-negative endocarditis

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.

Streptococci resident in the oral cavity have been linked to infective endocarditis (IE). While viridans streptococci are commonly studied and associated with IE, less research has been focused on Streptococcus pneumoniae. Two-component systems (TCSs), consisting of a histidine kinase (HK) protein and response regulator (RR) protein, are bacterial signaling systems that may mediate S. pneumoniae TIGR4 strain virulence in IE. To test this hypothesis, TCS RR mutants of TIGR4 were examined in vivo through use of rabbit models. There were 14 RR proteins identified and 13 RR mutants synthesized because SP_1227 was found to be essential. The requirement of the 13 RRs for S. pneumoniae growth in IE models was assessed by quantifying mutants after overnight inoculation in IE infected rabbits through use of real time PCR (qPCR), colony enumeration on antibiotic selection plates, and competitive index assays. Real time PCR pinpointed several candidate virulence factors. Candidate RR SP_0798 was selected to be further examined. In the in vivo model, mutant SP_0798 grew significantly less than our control mutant SP_1678, which encodes a hypothetical protein and grew at a comparable rate to wild-type TIGR4 strains. Literature and databases identified SP_0798 as the ciaR gene, which has roles in regulating many diverse cellular functions. Our data suggests that RR SP_0798 is a virulence factor of S. pneumoniae TIGR4 strain in IE. This research may place more emphasis on virulence factors and lead to novel methods to combat pneumococcal endocarditis.

Streptococcus sanguinis is an important component of the dental plaque biofilm and is believed to play a beneficial role in the oral cavity. S. sanguinis is also a leading cause of infective endocarditis (IE), a potentially lethal infection of the cardiac valves. S. sanguinis possesses genetic competence, the ability to acquire exogenous DNA into its genome. In the well characterized system of S. pneumoniae, genetic competence requires a quorum sensing system encoded by the early comCDE genes, as well as late genes controlled by the alternate sigma factor, ComX. Previous studies in other streptococcal species have suggested functions for the com regulon apart from DNA uptake. Here we characterized functions of the S. sanguinis com regulon genes in genetic competence, IE virulence, and biofilm formation. Our findings indicated that the early regulatory genes and those under the control of ComX in S. sanguinis play similar roles in genetic competence as their orthologs in other competent streptococci; however the sequence and mechanism of processing of the quorum sensing signal, competence-stimulating peptide, CSP, were determined to be unique. Using a rabbit endocarditis model, we determined that the comCDE and comX genes were not required for virulence, bacteremia, or pathology under a variety of infection conditions. In contrast, examination of biofilms by microscopy and crystal violet staining indicated that S. sanguinis CSP enhanced biofilm formation in a comDE-dependent manner. Deletion of the early com gene SSA_0195 eliminated this effect, while expression of the gene from an inducible promoter increased biofilm formation in the absence of CSP. Deletion of the comX gene resulted in biofilms with increased staining, cell death, and profoundly altered structure. Treatment with DNase I reduced biofilm formation in a com-independent manner. Taken together, these results suggest that expression of SSA_0195 is both necessary and sufficient for CSP-dependent biofilm enhancement, and that the late gene activator, ComX, is required to maintain normal biofilm architecture. Our findings suggest the com regulon of S. sanguinis may be an important determinant of competitiveness in the mouth, where native CSP production may occur at levels sufficient to influence biofilm formation.

L’endocardite infectieuse est une maladie grave dont sont victimes chaque année près de 2000 personnes en France et 17000 aux Etats-Unis. Malgré les progrès thérapeutiques, le taux de décès reste encore élevé avec des chiffres d’environ 20% pour la seule période hospitalière. Ces échecs sont en partie la conséquence d’un diagnostic souvent trop tardif et d’une évaluation pronostique insuffisante. En effet, il semble que la stratégie pour réduire la mortalité repose sur l’utilisation de nouveaux outils pour un diagnostic et une stratification du risque plus rapides, une diminution du délai d’instauration du traitement antibiotique, un transfert des patients à haut risque vers des centres médico-chirurgicaux spécialisés, des indications chirurgicales plus larges et un suivi prolongé.Depuis plusieurs années nous avons développé un programme de recherche basé sur une étroite collaboration entre les chercheurs de l’UMR 6236-CNRS et les médecins et chirurgiens des services de cardiologie et de chirurgie cardiaque. Cette thèse rapporte les résultats de cette recherche translationnelle sur la prise en charge des endocardites, synthèse de l’expérience clinique et fondamentale acquise par notre équipe. Nous avons démontré que la standardisation des processus de diagnostic et de décisions chirurgicales au sein d’une équipe multidisciplinaire permet de réduire la mortalité. Afin d’améliorer encore cette prise en charge, des innovations telles que l’utilisation de nouveaux marqueurs biologiques représente une approche importante. A partir d’une analyse du profil transcriptionnel propre à l’endocardite, nous avons pu identifier plusieurs gènes fortement impliqués dans la physiopathologie de la maladie. Ainsi, ces travaux montrent que la métalloproteinase-9 de la matrice extracellulaire, la S100A11 et l’aquaporine-9 constitueraient de nouveaux biomarqueurs pour le diagnostic et la prédiction des complications des endocardites. / Infective endocarditis is a serious disease affecting around 2000 patients in France and 17000 in the United-States. Despite therapeutic progress, in-hospital mortality remains high, around 20%. This is mainly the consequence of a too late diagnosis and insufficiencies in the risk stratification. In fact, novel perspectives on the management of endocarditis are emerging and offer a hope for decreasing the rate of residual deaths by accelerating the process of diagnosis and risk stratification, a reduction of delays of instauration of antimicrobial therapy, the rapid transfer of high-risk patients to specialised medio-surgical centres, the development of new surgical modalities, and close long-term follow-up.Since many years, we have developed, in our institution, a research program based on a close collaboration between the researchers of the UMR 6236-CNRS and the physicians and the surgeons of the Cardiology and Cardiac Surgery Departments. This thesis reports the results of this translational research on the management of endocarditis. We have demonstrated that the standardization of the diagnostic process and of the surgical indications reduces infective endocarditis-related mortality in infective endocarditis. To improve the management, innovations such as the use of new biomarkers represent a critical new approach for this disease. From a transcriptional based approach, we have identified several new genes strongly involved in the pathophysiology of infective endocarditis. Thus, our works shows that the matrix metalloproteinase-9, S100A11 and aquaporin-9 would be potential new biomarkers for the diagnosis and the prediction of complications during infective endocarditis.

M.Med.(Internal Medicine), Faculty of Health Sciences, University of the Witwatersrand, 2009. / In Africa, infective endocarditis (IE) is still a disease of young adults with underlying rheumatic heart disease (RHD). As of 2006, almost two-thirds of all persons infected with human immunodeficiency virus (HIV) are living in sub-Saharan Africa. Southern Africa thus remains the epicentre of the global HIV epidemic. The HIV sero-prevalence data reported in Southern Africa are as high as 20% - 30% of the adult population aged between 15 and 49 years. In South Africa, the prevalence of HIV among adults aged 15 - 49 is 18.8%. Based on a simple extrapolation, there is a higher possibility of encountering a significant number of patients infected with HIV and underlying RHD with IE in Southern Africa than in any other part of the world. In Africa because both HIV and valvular heart disease are relatively common, the co-existence of the two conditions in individual patients is not rare. Despite the major advances in diagnosis and management of this classical disease, the overall mortality rates for both native-valve and prosthetic-valve endocarditis remain as high as 20 to 25 percent after 1 year and at 50% after 10 years. However, the mortality rate varies, depending on a number of factors, such as: • the causative microorganism • the presence of complications • the development of perivalvular extension or a myocardial abscess • neurological events • the existence of conditions such as congestive heart failure • renal failure • severe immunosuppression due to HIV infection in intravenous drug abusers • the use of combined medical therapy and surgical therapy in appropriate patients. vi The clinical outcome of infective endocarditis in HIV patients is poor, severe immunodeficiency in IVDAs with IE has been reported to be associated with poor outcome. However, such an association has never been documented in non-IVDAs, particularly in Africa, where the expected majority patients with HIV and IE are non- IVDAs. The clinical profile including bacteriology of infective endocarditis in HIV patients is different from HIV uninfected patients. The clinical impact of the HIV epidemic on infective endocarditis in Africa has not been elucidated in the world literature and there is, moreover, a paucity of literature describing this clinical entity of HIV and IE in Africa. Objective The objective of this study was to highlight the co-existence of infective endocarditis in HIV positive, non-intravenous drug abuse in South Africa and Africa by: reporting three cases admitted at the researcher’s institution within a period of two months; and undertaking a literature review. Methods This was a retrospective case report and literature review study of IE in HIV infected patients. Three HIV positive patients with IE and with or without underlying chronic rheumatic heart disease were reported. The patients were admitted at the researcher’s institution within a period of two months. All three patients did not report intravenous drug abuse. However, all patients died within a short period of admission to the hospital. The systematic review of cases published in the literature was delivered from MEDLINE SEARCH from January 1985 to December 2006. The following key words were used: Human Immunodeficiency Virus, Acquired Immunodeficiency Syndrome, Rheumatic Heart Disease, Infective Endocarditis, and Intravenous Drug Abusers and Non-Intravenous Drug Abusers. Most of the articles were identified in English; where articles were identified in Spanish and French, only abstracts were used. vii Literature emanating from Africa was emphasized. In addition, the references quoted in this study were reviewed for relevance on the topic. Results Three patients with definitive IE and infected with HIV were reported: one patient was without underlying chronic rheumatic valvular heart disease and two showed underlying chronic rheumatic valvular heart disease. There are few reported studies of IE not related to intravenous drug abuse in HIV infected patients in the literature, which is probably attributable to the reported low prevalence of IE in this sub-group of patients. Most of these published studies are limited to a series of case reports and very little data or reports originate from Africa. Conclusion The clinical pattern of IE in HIV positive patients who are not IVDAs is not well described in literature. However, in this anecdotal case report, the three patients studied retrospectively had a poor outcome. Based on this anecdotal report of three cases described, if an extrapolation was done from these numbers and a prospective analysis performed, we would observed a substantial number of non-IVDU cases with infective endocarditis and HIV/AIDS in Africa. The literature review in its current form may shed some light on HIV and IE in non-IVDU patients, but doesn’t specifically address the issue of the potential co-existence of HIV and IE in Africa. Given the high prevalence both HIV/AIDS and rheumatic valvular heart disease in Africa, in future, we are more likely to see a significant proportion of patients with IE and underlying rheumatic valvular heart disease who are coincidentally HIV infected. There is a useful need for prospective studies describing the prevalence and outcome and for subsequently defining the management of this condition in Africa.

Made available in DSpace on 2016-01-26T12:51:34Z (GMT). No. of bitstreams: 1 siriohassemsobrinho_tese.pdf: 4305683 bytes, checksum: 9e829b180193bd2845ed65aadcd1897c (MD5) Previous issue date: 2010-07-16 / Bacterial endocarditis is a serious infectious disease, the treatment of which is traditionally performed with the patient hospitalized and receiving intravenous medication. When the etiological agent is Streptococcus, progression is generally less aggressive. Thus, the possibility of outpatient treatment becomes an attractive option from the social and economic standpoint. In the literature, this type of treatment is known as outpatient parenteral antimicrobial therapy (OPAT). Objective: The aim of the present study was to demonstrate that outpatient treatment is safe and effective in cases of streptococcic endocarditis. Patients and Methods: Six patients with bacterial endocarditis, diagnosed using the modified Duke University criteria, were followed up between January 2006 and November 2008. Four patients were female (66.6%) and two were male (33.4%). Mean age was 47.8 years, ranging from 32 to 65 years. All patients were eligible for outpatient treatment and agreed to take part in the study, having been either partially or wholly treated in an outpatient regimen. xiii Imaging and laboratory exams were performed at the beginning and end of treatment and when otherwise deemed necessary. Results: All patients progressed with no complications and with the complete resolution of the infection. The results of the laboratory and imaging exams are presented and discussed. Conclusion: Streptococcic bacterial endocarditis may be safely and effectively treated in an outpatient regimen for selected patients with no concomitant aggravating factors. / A Endocardite bacteriana é uma grave doença infecciosa cujo tratamento é tradicionalmente feito com o paciente internado, recebendo medicação intravenosa. As endocardites cujo agente etiológico é o Streptococcus costumam ter evolução menos agressiva. Assim, a possibilidade de tratamento ambulatorial passa a ser atraente tanto do ponto de vista social como econômico. Esse tipo de tratamento é conhecido na literatura pela sigla OPAT (Outpatient Parenteral Antimicrobial Therapy) Objetivo: O objetivo deste estudo foi demonstrar que, em casos de endocardite estreptocócica bem selecionados, o tratamento ambulatorial é seguro e eficaz. Casuística e Método: Foram acompanhados seis pacientes com endocardite bacteriana por Streptococcus, diagnosticados pelos critérios modificados da Universidade de Duke, no período de janeiro de 2006 a novembro de 2008. Quatro pacientes eram do sexo feminino (66,6%) e dois eram do sexo masculino (33.4%). A idade média foi de 47,8 anos, variando de 32 a 65 anos. xi Todos os pacientes que eram elegíveis para o tratamento ambulatorial concordaram em fazer parte do estudo tendo sido tratados parcialmente ou integralmente em regime ambulatorial. Os exames de imagem e laboratoriais eram feitos no início e ao final do tratamento ou de acordo com a necessidade Resultado: Todos evoluíram sem complicações e com resolução completa do quadro infeccioso. São apresentados e comentados os resultados evolutivos dos exames laboratoriais e de imagem realizados. Conclusão: A endocardite bacteriana Estreptocócica pode ser tratada de forma segura em regime ambulatorial em pacientes selecionados, nos quais não existe concomitância de fatores agravantes, com conseqüente benefício para o paciente.