重庆医科大学：《内科学》课程授课教案（留学生）infective endocaditis - 邓昌明

重庆医科大学第二临床学院尼泊尔教案 2008年12月3日 授课题目：Infective endocarditis 授课教师：邓昌明副教授 授课对象：2005级尼泊尔留学生 学时：3学时 目的要求： l、掌握Infective endocarditis的概念、分类、发病因素、发病机理、病理改变、 临床表现及基本防治方法。 2、熟悉Infectiveendocarditis的诊断和治疗原则。 重点：Infectiveendocarditis的鉴别诊断，治疗原则和措施。 难点：Infective endocarditis诊断及处理。 采用教具及电化器材：幼灯片、图片、多媒体投影。 教学内容、方法及时间分配： 首先介绍一典型的Infective endocarditis病例，就此引入本文的正题【多媒体投 影。 Definition(12min) Infective endocarditis(IE)is the condition in which there is microbial infection of the endothelial Surface of the heart.The characteristic lesion,the vegetation,is a variably sized mass of Platelets and fibrin in which abundant microorganisms and a little inflammatory cells are enmeshed.Heart valves are most commonly involved however,infection may occur at the site of a septal defect or on chordae tendineae or mural endocard-ium.Many diverse species of bacteria,fungi,mycobacteria, rickettsiae,chlamydiae,and myoplasma Cause IE:nevertheless,Streptococci, and fastidious gram that reside in the oral cavity and upper respiratorytract cause the majority of cause of IE has traditionally been classified as acute or subacute,the acute IE has marked systemic toxicity and is dead in days to less than 6 weeks.the latter is a case of an indolent.less toxic illness resulting in death in 6 weeks to 6 months or more.Toda marked xi and eral weekso weeks to months with only modest toxicity and rarely causes metastatic infection. Acute IE is caused by staphylococcus aureus,whereas the subacute syndrome is more likely caused by viridans streptococci,enterococci,coagulase-negative staphylococci, was 4.2 per 100.000 patient-years from 1970 to 1987.during the 1980's.the yearly incidence of IE per 100.000 population ranged from 1.7 to 2.0.Endocarditis occurred more frequently in men. valve prolapse,degenerative heart disease asymmetrical septal hypertrophy.or intravenous drug abuse.but predisposing conditions cannot be identified in 25 to 45

重庆医科大学第二临床学院尼泊尔教案 2008 年 12 月 3 日 授课题目：Infective endocarditis 授课教师：邓昌明副教授 授课对象：2005 级尼泊尔留学生 学时：3 学时 目的要求： 1、掌握 Infective endocarditis 的概念、分类、发病因素、发病机理、病理改变、 临床表现及基本防治方法。 2、熟悉 Infective endocarditis 的诊断和治疗原则。 重点：Infective endocarditis 的鉴别诊断，治疗原则和措施。 难点：Infective endocarditis 诊断及处理。 采用教具及电化器材：幼灯片、图片、多媒体投影。 教学内容、方法及时间分配： 首先介绍一典型的 Infective endocarditis 病例，就此引入本文的正题【多媒体投 影】。 Definition(12min) Infective endocarditis (IE) is the condition in which there is microbial infection of the endothelial Surface of the heart. The characteristic lesion, the vegetation, is a variably sized mass of Platelets and fibrin in which abundant microorganisms and a little inflammatory cells are enmeshed. Heart valves are most commonly involved; however, infection may occur at the site of a septal defect or on chordae tendineae or mural endocard-ium. Many diverse species of bacteria, fungi, mycobacteria, rickettsiae, chlamydiae, and myoplasma Cause IE; nevertheless, Streptococci, staphylococci, enterococci, and fastidious gram-negative coccobacilli that reside in the oral cavity and upper respiratory tract cause the majority of cause of IE. IE has traditionally been classified as acute or subacute, the acute IE has marked systemic toxicity and is dead in days to less than 6 weeks, the latter is a case of an indolent, less toxic illness resulting in death in 6 weeks to 6 months or more. Today acute IE presents with marked toxicity and progresses over days to several weeks to valvular destruction and metastatic infection. In contrast, subacute IE evolves over weeks to months with only modest toxicity and rarely causes metastatic infection. Acute IE is caused by staphylococcus aureus, whereas the subacute syndrome is more likely caused by viridans streptococci, enterococci, coagulase-negative staphylococci, or gram-negative coccobacilli. Epidemiology(15min) The incidence of IE is remarkably similar in developed Countries. the incidence of IE was 4.2 per 100,000 patient-years from 1970 to 1987. during the 1980’s, the yearly incidence of IE per 100,000 population ranged from 1.7 to 2.0. Endocarditis occurred more frequently in men. From 55 to 75 per cent of patients with native valve endocarditis (NVE) have predisposing conditions: rheumatic heart disease, congenital heart disease, mitral valve prolapse, degenerative heart disease asymmetrical septal hypertrophy, or intravenous drug abuse. but predisposing conditions cannot be identified in 25 to 45

per cent of patients.The namre of predisposing conditions and in par.the microbiology of correlate with the age of patients Clinical classification(12min) Cases of IE occurring in defined populations or settings often share clinical features and microbiology. Children The i cidence of IE among hospitalized children ranges from Iin4500 toI in2800 IE has been noted in neonates.with increasing frequency among neonates.IE is associated with very high mortality rates. Adults some of the common features and evolving aspects of IE occurring in adults have been noted in considering the epidemiology of IE.Mitral valve prolapse has emerged as a predominant p edisn sing for 7o30 per cent of NVE no abuse o in case-control studies,the relative risk of endocarditis among patients with mitral valve prolapse range from 3.5 to 8.2.Risk is also increased among men and patients over age 45.The mortality rate was 14 per cent.similar to rates noted in nie in general Rheumatic heart dis s the cent of cases in the1970 ing cardiac lesion for IE in 20 to 25 per endocarditis occurs most frequently on the mitral valve.the aortic valve is the next most common site for lE. Congenital heart disease is the substrate for IE in 10 to 20 per cent of younger adults and per cent of oder adults the common predisposing lesions are ventricular septal defects and biscuspid aortic va Intravenous drug abusers The risk for IE among intravenous drug abusers,2 to 5 per cent per patient-year,is estimated to be severalfold greater than that of patients with rheumatic heart disease or prosthetic valves.Endocarditis occurring in intravenous drug abusers has a unique property to infect right heart valves. ntra abus is a risk factorfo nt NVE. Prosthetic valve endocarditis(PVE)Epidemiologic stdies suggest that PVp comprises 10 to 20 per cent ofall cases of IE in developed countries.PVE has been called“earb”when symptoms begin within60 days of valve surgery and“late”wih onset thereafter patients with antecedent native valve endocarditis.particularly if active,are at increased risk for PVE. Etiological Microoganisms(5min) Viridans streptococci.These streptococci,which cause 30 to 65 per cent of NVE unrelated to drug abuse Streptococcus bovis and other streptococci s.bovis.part of the gastrointestinal tract noma fora causes 2.per cent of the episodes of streptococ.CoupA streptococci.which can infe vahves,caus Streptococcus pneumoniae.Although pneumococcal bacteremia occurs frequently,S. pneumoniae accounts for I to 3 per cent of NVE cases. Staphylococci S.aureus is main cause of acute IE,but S.bovis is major cause of subacute IE

per cent of patients. The nature of predisposing conditions and in part, the microbiology of IE correlate with the age of patients. Clinical classification(12min) Cases of IE occurring in defined populations or settings often share clinical features and microbiology. Children The incidence of IE among hospitalized children ranges from 1 in 4500 to 1 in 2800. Recently. IE has been noted in neonates. with increasing frequency among neonates. IE is associated with very high mortality rates. Adults some of the common features and evolving aspects of IE occurring in adults have been noted in considering the epidemiology of IE. Mitral valve prolapse has emerged as a predominant predisposing structural cardiac abnormality and accounts for 7 to 30 per cent of NVE in adults which is not related to drug abuse or nosocomial infection. in case-control studies, the relative risk of endocarditis among patients with mitral valve prolapse range from 3.5 to 8.2. Risk is also increased among men and patients over age 45. The mortality rate was 14 per cent, similar to rates noted in NVE in general. Rheumatic heart disease was the predisposing cardiac lesion for IE in 20 to 25 per cent of cases in the 1970’s and 1980’s. In patients with rheumatic heart disease, endocarditis occurs most frequently on the mitral valve, the aortic valve is the next most common site for IE. Congenital heart disease is the substrate for IE in 10 to 20 per cent of younger adults and 8 per cent of older adults the common predisposing lesions are ventricular septal defects and biscuspid aortic valves. Intravenous drug abusers The risk for IE among intravenous drug abusers, 2 to 5 per cent per patient-year, is estimated to be severalfold greater than that of patients with rheumatic heart disease or prosthetic valves. Endocarditis occurring in intravenous drug abusers has a unique property to infect right heart valves, intrarenous drug abuse is a risk factor for recurrent NVE. Prosthetic valve endocarditis(PVE) Epidemiologic studies suggest that PVE comprises 10 to 20 per cent of all cases of IE in developed countries. PVE has been called “early” when symptoms begin within 60 days of valve surgery and “late” with onset thereafter, patients with antecedent native valve endocarditis, particularly if active, are at increased risk for PVE. Etiological Microoganisms(5min) Viridans streptococci. These streptococci, which cause 30 to 65 per cent of NVE unrelated to drug abuse. Streptococcus bovis and other streptococci S. bovis, part of the gastrointestinal tract normal flora, causes 27 per cent of the episodes of streptococcal NVE. Group A streptococci, which can infect normal valves, cause rare episodes of endocarditis. Streptococcus pneumoniae. Although pneumococcal bacteremia occurs frequently, S. pneumoniae accounts for 1 to 3 per cent of NVE cases. Staphylococci S. aureus is main cause of acute IE, but S. bovis is major cause of subacute IE

Funci candida albicans and non-albicans candida species are the most common of the many funga PATHOGENESIS(15min) The pathogenesis of IE is not filly elucidated.The interactions between the human host and selected microorganisms that culminate in IE involve the vascular endothelium.hemostatic mechanisms.the host immune system.gross anatomic abnor ities in the heart,surfa properties of microorganisms.and peripherd events that initiate bacteremia.Each component of these interactions is in itself complex.infhenced by many factors,it is hypothesized that platelet-fibrin deposition occurs spontaneously in persons vulnerable to endocarditis and that these deposits, called nonbacterial thrombotic endocarditis (NBTE)are the sites at which organisms adhere to initiate IE. nbacteria l thro nbotic endocardi Two major mechanisms are very important in the formation of NBTE,endothelial injury and a hypercoagulable state.NBTE has been found in 1.3 per cent of patients at autopsy and,while present at all ages,is more common with increasing age.The sites of these NBTE correspond closely with the location of infected vegetations in patients withIE. Three hemodynamic circumstances may injure th initiating NBTE:(1) high-velocity jet impacting endothelium;(2)flow from a high-to a low-pressure chamber;(3)flow across a narrow orifice at high velocity.The flow through a narrowed orifice deposited bacteria maximally at the low-pressure sink immediately beyond an orifice or at the site where a jet stream impacts a surface.These are the same sites whe h】 hemo lances. Conversion of NBTE to IE The initiating event that utimately converts NBTE to IE is the entry of microorganisms into the circulation as a consequence of localized infection or trauma to a body surface.The frequency and magnitude of bacteremia associated with dail activities and health care procedures appear related to specific mucosa sufaces and skm.the ing bacteria. the dis ease state of the suface.and the extent of the local traume Bacteremia rate are highest fo that traumatize the oral mucosa,particularly the gingiva,and progressively decrease with procedtues involving the genitourinary tract and the gastrointestinal tract Although IE develops when circulating microorganisms are deposited at a site of NBTE.the coincidence of bacteremia cause IE the and NBTE does not uiformly result in IE.To ust be able to persist mu nd propagate m This requires resistance tohost defenses After adherence to the NBTE or endothelium (in the case of virulent organisms) Persistence and multiplication result in a complex dynamic process during which the infected vegetation increases in size by platelet-fibrin aggregation.microorganisms are shed into the blood,and vegetation fragm ents lize.Staphyloc nccmd promote and growth of the vegetation The vegetation has been considered a sheltered site wherein bacteria were protected from polymorphonuclear leukocytes PATHOPHYSIOLOGY(12min) Aside from the constitutional symptoms of infection,which are likely mediated by

Funci candida albicans and non-albicans candida species are the most common of the many fungal organisms identified as causing IE. PATHOGENESIS(15min) The pathogenesis of IE is not fully elucidated. The interactions between the human host and selected microorganisms that culminate in IE involve the vascular endothelium, hemostatic mechanisms, the host immune system, gross anatomic abnormalities in the heart, surface properties of microorganisms, and peripheral events that initiate bacteremia. Each component of these interactions is in itself complex, influenced by many factors, it is hypothesized that platelet-fibrin deposition occurs spontaneously in persons vulnerable to endocarditis and that these deposits, called nonbacterial thrombotic endocarditis (NBTE), are the sites at which microorganisms adhere to initiate IE. Development of nonbacterial thrombotic endocarditis Two major mechanisms are very important in the formation of NBTE, endothelial injury and a hypercoagulable state. NBTE has been found in 1.3 per cent of patients at autopsy and, while present at all ages, is more common with increasing age. The sites of these NBTE correspond closely with the location of infected vegetations in patients with IE. Three hemodynamic circumstances may injure the endothelium, initiating NBTE: (1) a high-velocity jet impacting endothelium; (2) flow from a high-to a low-pressure chamber; (3) flow across a narrow orifice at high velocity. The flow through a narrowed orifice deposited bacteria maximally at the low-pressure sink immediately beyond an orifice or at the site where a jet stream impacts a surface. These are the same sites where NBTE forms as a result of hemodynamic circumstances. Conversion of NBTE to IE The initiating event that ultimately converts NBTE to IE is the entry of microorganisms into the circulation as a consequence of localized infection or trauma to a body surface. The frequency and magnitude of bacteremia associated with daily activities and health care procedures appear related to specific mucosal surfaces and skin, the density of colonizing bacteria, the disease state of the surface, and the extent of the local trauma. Bacteremia rates are highest for events that traumatize the oral mucosa, particularly the gingiva, and progressively decrease with procedures involving the genitourinary tract and the gastrointestinal tract. Although IE develops when circulating microorganisms are deposited at a site of NBTE, the coincidence of bacteremia and NBTE does not uniformly result in IE. To cause IE the organism must be able to persist and propagate on the endothelium. This requires resistance to host defenses. After adherence to the NBTE or endothelium (in the case of virulent organisms). Persistence and multiplication result in a complex dynamic process during which the infected vegetation increases in size by platelet-fibrin aggregation, microorganisms are shed into the blood, and vegetation fragments embolize. Staphylococci and streptococci promote platelet aggregation and growth of the vegetation. The vegetation has been considered a sheltered site wherein bacteria were protected from polymorphonuclear leukocytes. PATHOPHYSIOLOGY(12min) Aside from the constitutional symptoms of infection, which are likely mediated by

cvtokines the clinical manifestations of ie result from (1)the local destructive effects of intracardiac infe tion;(2)the emboliza tion of bland oi sep fragments vegetations to distant sites,resulting in infarction or infection:(3)the hematogenou seeding of remote sites during continous bacteremia;and(4)an antibody response to the infecting organism with subsequent tissue injury due to deposition of preformed immune complexes or antibody-complement interaction with antigens deposited in tissues The intr cardiac consequences of IE range from an attendant tissue damage catastrophic,when infection is locally destructive or extends beyond the valve leaflet. Distortion of valve leaflets,rupture of chordae tendineae,and performations or fistulas between major vessels and cardiac chambers or between chambers themselves as a consequence of burrowing infection may result in progressive congestive heart Infection,particularly that involving the aortic valve or prosthetic valves,may extend into paravalvular tissue and result in abscesses and persistent fever,disruption of the conduction system with electro cardiographic conduction abnormalities and relevant arhythmias,or purulent pericarditis.Large vegetations,particularly at the mitral can onal valvular stenos and her ynami dent in I 1 to 43 per cent ofpatients The persistent bacteremia of IE.with or without septic emboli.may result in metastatic infection.In general,these infections originate before initiation of antimicrobial therapy:however:clinical manifestation may be delayed.These infections may pre t as local sig and s ymp toms or as sistent fever during therapy:Any organ or tissue may be infected,including the e spleen,kidney,brair meninges,pericardium,bone,synovium,and even vitreous humor Metastati abscesses are often small and miliary.And the humoral and cell-mediated arms of the immune system are stimulated in patient with IE. CLINICAL FEATURES min) The interval be we en the med initiating bacteremiand of symptomsof E is short.It is estimated that more than 80 per cent of patients with NVE develop symptoms within 2 weeks.Interestingly,in some patients with intraoperative or perioperative infection of prosthetic valves.the incubation period may be prolonged to 5 or more months) Fever is the most com on symptom and sign in patients with IE.In patients with subacute IE not associated with rigors.Fever may be absent or minimal in the elderly or in those with congestive heart failure,severe debility.or chronic renal failure and occasionally in patients with nie caused by coagulase-negative staphylococci. Heart murmurs are noted in 80 to 85 per cent of patients with NVE and are emblematic of the les on pre to IE.Murmu only not audible i patients with tricuspid valve IE.Similarly,in acute NVE due to S.aureus,murmurs are heard in only 30 to 45 per cent of patients on initial evaluation but are ultimately noted in 75 to 85 per cent.The new or changing murmurs are relatively in-frequent in subacute NVE and are more prevelent in acute IE and PVE.They are frequently

cytokines, the clinical manifestations of IE result from (1) the local destructive effects of intracardiac infection; (2) the embolization of bland or septic fragments of vegetations to distant sites, resulting in infarction or infection; (3) the hematogenous seeding of remote sites during continous bacteremia; and (4) an antibody response to the infecting organism with subsequent tissue injury due to deposition of preformed immune complexes or antibody-complement interaction with antigens deposited in tissues. The intracardiac consequences of IE range from an attendant tissue damage to catastrophic, when infection is locally destructive or extends beyond the valve leaflet, Distortion of valve leaflets, rupture of chordae tendineae, and performations or fistulas between major vessels and cardiac chambers or between chambers themselves as a consequence of burrowing infection may result in progressive congestive heart failure. Infection, particularly that involving the aortic valve or prosthetic valves, may extend into paravalvular tissue and result in abscesses and persistent fever, disruption of the conduction system with electro cardiographic conduction abnormalities and relevant arrhythmias, or purulent pericarditis. Large vegetations, particularly at the mitral valve, can result in functional valvular stenosis and hemodynamic deterioration. Embolization of fragments from vegetations is evident in 11 to 43 per cent of patients. The persistent bacteremia of IE, with or without septic emboli, may result in metastatic infection. In general, these infections originate before initiation of antimicrobial therapy; however, clinical manifestation may be delayed. These infections may present as local signs and symptoms or as persistent fever during therapy. Any organ or tissue may be infected, including the spleen, kidney, brain, meninges, pericardium, bone, synovium, and even vitreous humor. Metastatic abscesses are often small and miliary. And the humoral and cell-mediated arms of the immune system are stimulated in patient with IE. CLINICAL FEATURES(9min) The interval between the presumed initiating bacteremia and the onset of symptoms of IE is short. It is estimated that more than 80 per cent of patients with NVE develop symptoms within 2 weeks. Interestingly, in some patients with intraoperative or perioperative infection of prosthetic valves, the incubation period may be prolonged (2 to 5 or more months). Fever is the most common symptom and sign in patients with IE. In patients with subacute IE, fevers are low grade, rarely exceeding 39.4℃， remittent, and usually not associated with rigors. Fever may be absent or minimal in the elderly or in those with congestive heart failure, severe debility, or chronic renal failure and occasionally in patients with NVE caused by coagulase-negative staphylococci. Heart murmurs are noted in 80 to 85 per cent of patients with NVE and are emblematic of the lesion predisposing to IE. Murmurs are commonly not audible in patients with tricuspid valve IE. Similarly, in acute NVE due to S. aureus, murmurs are heard in only 30 to 45 per cent of patients on initial evaluation but are ultimately noted in 75 to 85 per cent. The new or changing murmurs are relatively in-frequent in subacute NVE and are more prevelent in acute IE and PVE. They are frequently

important harbingers of congestive hear failre Enlargement of spleen is noted less commonly in recent reports than previously.and it is more common in subacute IE of long duration. Although 50 per cent of patients with IE were reported to have one or more of the classic peripheral manifestations of this illess,these findings are encountered less frequently today. Petechiae the most common of these manifestations.are found on the palpebra conjunctiva.the buccal and palatal mucosa,and the extremities Splinter of subungual hemorrhages are the dark red.linear or occasionally flame-shaped streaks in the nail bed of the fingers or toes. Osler's nodes are small.tender subcutaneous nodules that develop in the pulp of the digits or occasionally more proximally in the fingers and persist for hours to several days Roth spots,oval retinal hemorrhages with pale centers.are infrequent findings in patients with Ie. Janeway lesions are small erythematous or hemorrhagic macular nontender lesions on the palms and soles and are the consequence of septic embolic events. Musculoskeletal symptoms are common patienth IE.these inclucle arthralgias and myalgias Systemic emboli are among the most common clinical sequence of IE.occurring in up to 40 per cent of patients,and are frequent subclinical events found only at autopsy Emboli ofien antedate diagnosis.the incidence of embolic events decreases promptly administration Neursal smptoms and simns 30 n more frequent when IE is caused by S.anreus.and are associated with increased mortality rates.Neurological manifestation,such as a stroke.intracelebral hemorrage. or subarachnoid hemorrage.Severe headche seizure and encephalopathy Congestive heart failur nocrnptRPebea (CHE) ing IF is primarily the result of chordae Renal insufficiency as a result of immune complex-mediated glomerulonephritis occurs in less than 15 per cent of patients with IE focal glomerulonephritis and renal infarcts cause hematuria DIAGNOSISO5min) sym and sigr of endocarditisare ofe ofen resul from a complication of IE rather than rfect the intracardiac infectio itself.Consequentl.if physicians are to avoid overlooking the diagnosis of lE.a high index of suspicion must be investigated when patients with fever present with one or more of the cardinal elements of IE:a predisposing cardiac lesion or behavior pattern mbolic pheno and evidan active IE must be considered in a patient with significant valvular heart disease and persistent unexplained fever,in the intravenous drug abuser with fever especially if there is cough and pleuritic chest pain,or in the young patient with an unexpected stroke or subarachnoid hemorrhage.The development of a new regurgitant murmur must raise the possibility ofIE

important harbingers of congestive heart failure. Enlargement of spleen is noted less commonly in recent reports than previously, and it is more common in subacute IE of long duration. Although 50 per cent of patients with IE were reported to have one or more of the classic peripheral manifestations of this illess, these findings are encountered less frequently today. Petechiae the most common of these manifestations, are found on the palpebral conjunctiva, the buccal and palatal mucosa, and the extremities. Splinter of subungual hemorrhages are the dark red, linear or occasionally flame-shaped streaks in the nail bed of the fingers or toes. Osler’s nodes are small, tender subcutaneous nodules that develop in the pulp of the digits or occasionally more proximally in the fingers and persist for hours to several days. Roth spots, oval retinal hemorrhages with pale centers, are infrequent findings in patients with IE. Janeway lesions are small erythematous or hemorrhagic macular nontender lesions on the palms and soles and are the consequence of septic embolic events. Musculoskeletal symptoms are relatively common in patient with IE, these inclucle arthralgias and myalgias. Systemic emboli are among the most common clinical sequence of IE, occurring in up to 40 per cent of patients, and are frequent subclinical events found only at autopsy. Emboli often antedate diagnosis, the incidence of embolic events decreases promptly during the administration of effective antibiotic therapy. Neurological symptoms and signs occur in 30 to 40 per cent of patients with IE, are more frequent when IE is caused by S. anreus, and are associated with increased mortality rates. Neurological manifestation, such as a stroke, intracelebral hemorrage, or subarachnoid hemorrage. Severe headche seizure and encephalopathy. Congestive heart failure (CHF) complicating IE is primarily the result of valve destruction or distortion or rupture of chordae tendineae. Renal insufficiency as a result of immune complex-mediated glomerulonephritis occurs in less than 15 per cent of patients with IE focal glomerulonephritis and renal infarcts cause hematuria. DIAGNOSIS(15min) The symptoms and signs of endocarditis are often constitutional and when localized, often result from a complication of IE rather than reflect the intracardiac infection itself. Consequently, if physicians are to avoid overlooking the diagnosis of IE, a high index of suspicion must be investigated when patients with fever present with one or more of the cardinal elements of IE: a predisposing cardiac lesion or behavior pattern, bacteremia, embolic phenomenon, and evidence of an active endocardial process. IE must be considered in a patient with significant valvular heart disease and a persistent unexplained fever, in the intravenous drug abuser with fever especially if there is cough and pleuritic chest pain, or in the young patient with an unexpected stroke or subarachnoid hemorrhage. The development of a new regurgitant murmur must raise the possibility of IE

BAcTEREMIA positive blood cultures may stimulate consideration of ie as a possible diagnosis.Sustained low-level(organisms/ml)bacteremia or more are posirive,the diagnosis of must be considered A microbial cause for infective endocarditis is established by recovering the infection agent from the blood or from surgically removed endocardial vegetations or embolic material bacteremia in patients with endocarditis is continuous:hence.there is no tage to obtaining blood culmres in relationship to fever.Furth ore,blond arterial and venous source s are culture positive at simil rate In patients who have not received prior antibiotics and who will ultimately have blood culture-positive IE.it is likel that 95 to 100 per cent of all cultures obtained will be positive OBTAINING BLOOD CULTURE Three separate sets of blood culture,each from a obtained over 24 d to ev uate patient Laboratory Tests Blood Cultures are the crucial laboratory tests Used in the diagnosis of ie Other tests are inevitably obtained and merit mention.Anemia with normochromic norm wserum iron,and low iron-bindin sent of patlents anemla may be absent acute IE.Sbdeu IE the white blood cell count is usually normal:in contrast.a leukocytosis with increased segmented granulocytes is common in acute IE. The erythrocyte Sedimentation rate [ESR]is elevated (average about 55mm/hr)in almost all patients with IE. The urine e analysis is ofien abnormal even wher Proteinuria and microscopic hematuria are noted in 50 Per cent of Patient Echocardiography Evaluation of Patients with clinically suspected IE by this technique frequently allows the morphologic confirmation of infection and increasingly aids in decisions regarding management.Although many patients with g the aotic or mitral valv can be ima ged adeo atedly by echocardiography (TTE),transesophageal echocardiography (TEE)using biplan technology with incorporated color flow and continuous as well as pulsed Doppler is the state of the art.TEE allows visualization of smaller vegetations.M-mode is less sensitive than two-dimensinal echocardiography and TTe is less sensitive than Tee In spite of the sensitivity of TEE in detecting vegetations in patients with proven IE Echocardiography does not provide a specific diagnosis Vegetations and valve dysfunction may be demonstrated,but determination of causality requires clinical or direct anatomical and microbiological confirmation. TREATMENT(15min) mic ustbe eradicated.accomp plish this res infection Also. the invasive ,destructive intracardiac and focal extracardia complications of infection must be addressed if morbidity and mortality are to be minimized. In selecting antimicrobial therapy for patients with IE,the ability of potential agents

BACTEREMIA positive blood cultures may stimulate consideration of IE as a possible diagnosis. Sustained low-level(<100 organisms/ml) bacteremia or more are positive, the diagnosis of IE must be considered. A microbial cause for infective endocarditis is established by recovering the infection agent from the blood or from surgically removed endocardial vegetations or embolic material. Bacteremia in patients with endocarditis is continuous; hence, there is no advantage to obtaining blood cultures in relationship to fever. Furthermore, blood obtained from arterial and venous sources are culture positive at similar rates. In patients who have not received prior antibiotics and who will ultimately have blood culture-positive IE, it is likely that 95 to 100 per cent of all cultures obtained will be positive. OBTAINING BLOOD CULTURE Three separate sets of blood culture, each from a separate venipuncture, obtained over 24 hours, are recommended to evaluate patients with suspected endocarditis, one flask should be placed into at least 10 ml of blood. Laboratory Tests Blood Cultures are the crucial laboratory tests Used in the diagnosis of IE. Other tests are inevitably obtained and merit mention. Anemia, with normochromic normocytic red cell indices, a low serum iron, and low serum iron-binding capacity, is seen in 70 to 90 per cent of patients. anemia may be absent in acute IE, In Subacute IE the white blood cell count is usually normal; in contrast, a leukocytosis with increased segmented granulocytes is common in acute IE. The erythrocyte Sedimentation rate [ESR] is elevated (average about 55mm/hr) in almost all patients with IE. The urine analysis is often abnormal, even when renal function remains normal. Proteinuria and microscopic hematuria are noted in 50 Per cent of Patients. Echocardiography Evaluation of Patients with clinically suspected IE by this technique frequently allows the morphologic confirmation of infection and increasingly aids in decisions regarding management . Although many patients with NVE involving the aotic or mitral valve can be imaged adequatedly by transthoracic echocardiography (TTE), transesophageal echocardiography (TEE) using biplane technology with incorporated color flow and continuous as well as pulsed Doppler is the state of the art . TEE allows visualization of smaller vegetations. M-mode is less sensitive than two-dimensinal echocardiography and TTE is less sensitive than TEE . In spite of the sensitivity of TEE in detecting vegetations in patients with proven IE. Echocardiography does not provide a specific diagnosis , Vegetations and valve dysfunction may be demonstrated , but determination of causality requires clinical or direct anatomical and microbiological confirmation. TREATMENT(15min) Two major objectives must be addressed to effectively treat IE. The infecting microorganism must be eradicated .Failure to accomplish this results in relapse of infection . Also, the invasive ,destructive intracardiac and focal extracardiac complications of infection must be addressed if morbidity and mortality are to be minimized. In selecting antimicrobial therapy for patients with IE , the ability of potential agents

to kill the causative and minimum bac must be considered.The MIC is the lowest concentration that inhibits growth and the MBC is the lowest concentration that decreases a standard inoculum of organisms 99.9 per cent during 24 hours. Antimicrobial Therapy for specific organisms The antimicrobia therap agent but should do so while causing little or no toxicity.Therapy foragiven patien requires modidfication to accommodate end-organ dysfunction.existing allergies and other anticipated toxicities.With the exception of staphylococcal endocarditis,the antimicrobial regimens recommended for the treatment of patients with NVE and PVE e similar;altho ugh more p longed tre PENICILIN-SUSCEPTIBLE VIRI DANS STREPTOCOCCI OR STREPTOCOCCU BOVIS The 4-week regimens yield bacteriologic cure rates of 98 Per cent among Patients who complete therapy.Penicillin G of 12-18 million U is used(24 hours IV either continuously or every 4 hours in six equally divided doses).For the treatment of streptococcal endocarditis in patients with a history of immediate allergic reactions to a penicillin or cephalos vancomycin is recommended Patients with other forms of penicillin allergy may be treated cautiousl with the ceftriaxone regimen or with cefacolin,2 gm IV every 8 hours for 4 weeks. RELATIVELY PENICILLIN-RESISTANT STREDTOCOCCI.Approximately 15 per cent of streptococci that cause endocarditis are relatively resistant to penicillin effective tre can be lished with eithe vancomycin alone or by adding gentamicin to the initial 2 weeks of the ceftriaxone regimen STREPTOCOCCUS PYOGENS.STREPTOCOCCUS PNEUMO NIAE,AND GROUP B,C,and G STREPTOCOCCI Endocartditis caused by these streptococci has been either refractory to antibiotic therapy or associated with extensive valyular damage.Peni icillin G in a dose of 3 million every 4 hours for 4w eks is recom mended fo the treatm nt of group A streptococca and Pneumococcal endocarditis IE caused by group G,C or B streptococci is more difficult to treat than that caused by penicillin-susceptible viridans streptococci. consequently,the addition of gentamicin to the first 2 weeks of a 4-week regimen using high doses ofpenicillin is often advocated ENTEROCOCCI O for tero occal endocarditis ires the synergistic bactericidal interaction of an antimicrobial targeted against the bacterial cell wall (penicillin.ampicillin.or vancomvein)and an aminoglycoside that is able to exert a lethal effect(Primary streptomycin or gentamicin).The standard regimens recommended for the treatment of enterococcal endocarditis are designed to achieve bactericidal approximately 85 per cent.Therapy is administered for 4 to6weeks.with the nge course used to treat patients with IE that was symptomatic for more than 3 months ,with complicated disease,and when there is enterococcal PVE.During treatment careful clinical follow-up of patients and aminoglcoside levels is reauired to prevent nephrotoxicity

to kill the causative organism as well as the minimum inhibitory concentration (MIC) and minimum bactericidal concentration(MBC) of these antibiotics for the organism must be considered. The MIC is the lowest concentration that inhibits growth and the MBC is the lowest concentration that decreases a standard inoculum of organisms 99.9 per cent during 24 hours. Antimicrobial Therapy for specific organisms. The antimicrobial therapy for endocarditis should not only eradicate the causative agent but should do so while causing little or no toxicity . Therapy for a given patient requires modidfication to accommodate end-organ dysfunction, existing allergies ,and other anticipated toxicities . With the exception of staphylococcal endocarditis ,the antimicrobial regimens recommended for the treatment of patients with NVE and PVE are similar, although more prolonged treatment is often advised for patients with PVE. PENICILIN-SUSCEPTIBLE VIRIDANS STREPTOCOCCI OR STREPTOCOCCUS BOVIS The 4-week regimens yield bacteriologic cure rates of 98 Per cent among Patients who complete therapy . Penicillin G of 12-18 million U is used ( 24 hours IV either continuously or every 4 hours in six equally divided doses). For the treatment of streptococcal endocarditis in patients with a history of immediate allergic reactions to a penicillin or cephalosporin antibiotics , vancomycin is recommended . Patients with other forms of penicillin allergy may be treated cautiously with the ceftriaxone regimen or with cefazolin, 2 gm IV every 8 hours for 4 weeks. RELATIVELY PENICILLIN-RESISTANT STREDTOCOCCI. Approximately 15 per cent of streptococci that cause endocarditis are relatively resistant to penicillin . effective treatment can be accomplished with either vancomycin alone or by adding gentamicin to the initial 2 weeks of the ceftriaxone regimen. STREPTOCOCCUS PYOGENS, STREPTOCOCCUS PNEUMO￾NIAE, AND GROUP B , C, and G STREPTOCOCCI Endocartditis caused by these streptococci has been either refractory to antibiotic therapy or associated with extensive valvular damage. Penicillin G in a dose of 3 million units intravenously every 4 hours for 4 weeks is recommended for the treatment of group A streptococcal and Pneumococcal endocarditis . IE caused by group G, C or B streptococci is more difficult to treat than that caused by penicillin-susceptible viridans streptococci, consequently , the addition of gentamicin to the first 2 weeks of a 4-week regimen using high doses of penicillin is often advocated. ENTEROCOCCI Optimal therapy for enterococcal endocarditis requires the synergistic bactericidal interaction of an antimicrobial targeted against the bacterial cell wall (penicillin , ampicillin , or vancomycin) and an aminoglycoside that is able to exert a lethal effect (Primary streptomycin or gentamicin). The standard regimens recommended for the treatment of enterococcal endocarditis are designed to achieve bactericidal synergy. Synergistic combination therapy has resulted in cure rates of approximately 85 per cent . Therapy is administered for 4 to 6 weeks, with the longer course used to treat patients with IE that was symptomatic for more than 3 months ,with complicated disease, and when there is enterococcal PVE. During treatment ,careful clinical follow-up of patients and aminoglycoside levels is required to prevent nephrotoxicity and ototoxicity

cost-containment pressures frequently result in initiation of antimicrobial therapy for es have been obtai ined Patients must be monitored carefully during therapy and for several mohths thereafter to detect complications of endocarditis or therapy Surgical Treatment of intracardiac complications diac surg in intracardiac comp of endocarditis data suggest combines antibiotics and surgical intervention.Accordingly.these complications (for instance,Valvular dysfunction,unstable prosthesis,uncontrolled infection and relapse afier optimal therapy)have become indications for cardiac surgery. PREVENTION(I0mim) rationale for prophylaxis for endocarditis can be derived by considering the pathogenesis,epidemiology,and microbiology of the illness.This rationale,even in the absence of supporting clinical trials has generated recommendations for prophylaxis against endocarditis that are routinely applied in developed countries. GENERAL METHODS The incidence of IE otherwise predi tients to IE.patients with persisting congenital lesions and those with acquired Valvular heart disease who remain at risk for IE should be instructed regarding their risk for endocarditis and the potential benefits of antibiotic prophylaxis.Maintenance of may be a more than procedure-focused IE.some activi to induce bacteremia should be avoided.Infections associated with bacteremia must be treated promptly and if possible eradicated before the involved tissues are incised or manipulated. CHEMOPROPHYLAXIS The widely promulgated recommendations of antimicrobial prophylaxis for are based cumstantialevidencesuplemcntcdby studies of prophylaxis using animal models Even if antibiotic prophylaxis is effective as well as safe and inexpensive,only a small percentage of the cases are preventable

cost-containment pressures frequently result in initiation of antimicrobial therapy for suspected endocarditis immediately after blood cultures have been obtained. MONITORING THERAPY FOR ENDOCARDITIS Patients must be monitored carefully during therapy and for several mohths thereafter to detect complications of endocarditis or therapy. Surgical Treatment of Intracardiac Complications Cardiac surgical intervention plays an increasingly important role in the treatment of patients with intracardiac complications of endocarditis. Retrospective data suggest that mortality is unacceptably high when mortality is reduced when treatment combines antibiotics and surgical intervention . Accordingly, these complications (for instance, Valvular dysfunction, unstable prosthesis, uncontrolled infection and relapse after optimal therapy)have become indications for cardiac surgery. PREVENTION(10min) A rationale for prophylaxis for endocarditis can be derived by considering the pathogenesis, epidemiology, and microbiology of the illness . This rationale, even in the absence of supporting clinical trials has generated recommendations for prophylaxis against endocarditis that are routinely applied in developed countries. GENERAL METHODS The incidence of IE can be significantly reduced by total surgical correction of some congenital lesions that otherwise predispose patients to IE.patients with persisting congenital lesions and those with acquired Valvular heart disease who remain at risk for IE should be instructed regarding their risk for endocarditis and the potential benefits of antibiotic prophylaxis . Maintenance of good oral hygiene may be a more important preventive than procedure-focused chemoprophylaxis. Among Patients at risk for IE, some activities or prcocedurs likely to induce bacteremia should be avoided. Infections associated with bacteremia must be treated promptly and if possible eradicated before the involved tissues are incised or manipulated. CHEMOPROPHYLAXIS The widely promulgated recommendations of antimicrobial prophylaxis for endocarditis are based upon circumstantial evidence supplemented by studies of prophylaxis using animal models. Even if antibiotic prophylaxis is effective as well as safe and inexpensive, only a small percentage of the cases are preventable