Infective Endocarditis (IE) PDF

Infective endocarditis (IE) By Dr. Shereen M.M. Abdelaziz Associate Professor of Medical Microbiology & Immunology College of Medicine Objectives: ❑ List the causative microorganisms associated with IE ❑ Discuss the risk factors of IE...

Infective endocarditis (IE) By Dr. Shereen M.M. Abdelaziz Associate Professor of Medical Microbiology & Immunology College of Medicine Objectives: ❑ List the causative microorganisms associated with IE ❑ Discuss the risk factors of IE ❑ Understand the pathophysiology of IE ❑ Outline the clinical presentation and the course of IE ❑ Discuss the laboratory diagnosis of IE ❑ Discuss the most common microbiological characteristics of the causative pathogens  Definition: infectious inflammation of the endocardium that affects the heart valves. Etiology: The condition is a result of bacteremia, which is most commonly caused by dental procedures, surgery, distant primary infections, and non-sterile injections. Risk factors 1. Rheumatic heart disease 2. IV drug use 3. Immunosuppression 4. Prosthetic heart valve 5. Congenital heart disease  Main causative pathogens: Pathogen Characteristics Course of disease Streptococcus Normal flora of oral cavity Most common viridans and upper respiratory tract cause of subacute Common cause of IE IE, especially following dental surgical in previously procedures or extremely damaged heart poor oral hygiene valves Staphylococcus Affects previously healthy Most aureus valves common cause of Usually fatal (if left acute IE untreated)  Pathogen Characteristics Course of disease Staphylococcus Cause IE in patients with Common cause epidermidis peripheral venous of subacute (Coagulase -ve catheters, prosthetic heart S. aureus) valves or any prothesis Enterococcus Normal flora of human Subacute IE faecalis colon, urethra and female especially genital tract following urinary IE in patients with tract infections preexisting heart valve damage Less common pathogens (Subacute IE) Pathogen Characteristics Streptococcus Normal flora of colon gallolyticus IE associated with colorectal cancer in elderly and immunocompromised persons HACEK (G-ve Oropharyngeal flora bacilii) IV drug users who contaminate their Haemophylus needles with saliva Aggregatibacter Cardiobacterium In patients with poor dental Eikenella hygiene and/or periodontal infection Kingella Candida species Normal flora of mucous membrane Causes IE in immunosuppressed patients. IE often associated with vascular catheters Pathogenesis 1- Valvular endothelial damage as in cases of Rheumatic fever, Prosthetic Valve …etc. causes turbulent blood flow → fibrin-platelet aggregate on valve 2- Bacteremia: Bacterial colonization of damaged valve Further depositions of fibrin & platelets → Vegetations Valve destruction with loss of function  Clinical features: Constitutional symptoms (fatigue, fever/chills, malaise). Signs of pathological cardiac changes (e.g., new or changed heart murmur, heart failure signs). Possibly manifestations of subsequent damage to other organs (e.g., glomerulonephritis, septic embolic stroke).  Lab Diagnosis 1. Blood cultures (Before Antimicrobial therapy) The standard test to determine the microbiologic etiology of the disease. Standard blood culture of 5 days period allows recovery of most cultivable microorganisms including Candida and the fastidious HACEK organisms. Subculture on solid media to isolate the causative organism for its further identification (via morphology and biochemical reactions) and determination of antibiotic sensitivity pattern is mandatory. 2. Serology 3. PCR  Prophylaxis: Antibiotics are only administered in specific circumstances, e.g., in patients with preexisting heart conditions undergoing dental or surgical procedures. Prognosis: If left untreated, infective endocarditis can be fatal within a few weeks. MCQ: 1- Which of the following is not a character of staphylococcal infective endocarditis? A.Large vegetations seen on the valves B.Affects pre-damaged valves C.Most common cause of acute IE for all groups D.If left untreated becomes fatal within 6 weeks Which group of patients is risky for Streptococcus gallolyticus infective endocarditis? A. IV drug users who contaminate their needles with saliva B. Patients with colorectal cancer C. Patients in close contact with pets D. Patients with poor dental hygiene Enumerate: A. Three of the most common pathogens causing infective endocarditis. B. The standard test for diagnosis of infective endocarditis. C. Two risk factors for infective endocarditis. Complete: Regarding the clinical course, S. aureus causes …………….IE while Strept. viridans causes ……….IE  Rheumatic Fever By Dr. Shereen M.M. Abdelaziz Associate Professor of Medical Microbiology & Immunology College of Medicine Objectives: Identify the leading cause of the disease (post Streptococcus pyogenes infection) Understand the mechanism and pathophysiology of the disease Recognize the role of molecular mimicry and type II hypersensitivity State the diagnosis of the disease Learn the most important preventive measures Definition: Delayed complication that usually occurs 2–4 weeks after throat infection caused by group A β- hemolytic streptococcal (GAS). Epidemiology: Peak incidence: 5–15 years Prevalence: Developing countries: the most common cause of cardiovascular disease in children and adolescents Developed countries: rare Etiology: Most commonly accepted mechanism is Molecular mimicry: Streptococcus pyogenes possess antigenic determinants (M protein) that are similar to myosin of the heart tissues. In case of acute strep throat infection without antibiotic treatment → antibodies formed against M protein of the pathogen may cross react with myosin of the heart tissues and cause rheumatic fever. ❑ Rheumatic fever is not associated with streptococcal skin infections  Type II hypersensitivity reaction → acute inflammatory sequel Clinical features: Constitutional symptoms (fever , malaise, fatigue) + (J NES criteria): Joints: migratory poly-arthritis Heart: Pancarditis (endocarditis, myocarditis, and pericarditis). Subcutaneous nodules Erythema marginatum: Painless non-pruritic ring-like lesion on trunk Sydenham chorea: Involuntary irregular movements of the limbs, neck, head, and/or face.  Chronic valvular lesions can occur as a complication of acute rheumatic fever Diagnosis: based on the JONES criteria + evidence of a preceding throat GAS infection as confirmed by laboratory test. Confirmation of GAS infection ▪ ↑ Antistreptolysin O titer (ASOT) ▪ Positive rapid streptococcal antigen test from throat swab  Laboratory Tests Specimens: Swabs from throat and blood for serology N.B: Blood cultures are all negative 1. Rapid antigen detection test (RADT): in throat swabs. Negative result doesn’t confirm the absence of GAS. 2. Streptococcal antibody tests: a. Anti-streptolysin O test (ASO test): Streptolysin O: Protein toxin produced by GAS that causes lyses of RBCs (causes β-hemolysis when organism is cultured on blood agar) ASO: Host antibodies formed against the toxin. Antibody titers get raised within 1 week and reaches to the maximum level within 3-6 weeks post-infection. Anti-streptolysin O (ASO) antibody titers (≥ 200 Todd units) is CONFIRMATORY for Rheumatic Fever.  ASOT with titer= 1/400 Todd units b. Antideoxyribonuclease B: Titers get raised within 1-2 week and it reaches to the maximum level within 6-8 weeks. 3- PCR based diagnosis assay: PCR-based diagnosis is more exact than serology. It also helps in early diagnosis of rheumatic heart disease. 4- Acute phase reactants (ESR, CRP): Serum proteins synthesized by the liver. Elevated in cases of active RF as well as in other degenerative and inflammatory conditions. A positive CRP, and a high ESR are helpful in the diagnosis and follow up of cases of RF. Complications: ❑ Cardiac involvement is the most important prognostic factor during an initial rheumatic fever episode. ❑Early death in rheumatic fever is usually due to myocarditis. ❑Chronic valvular heart lesions cause recurrent episodes of rheumatic heart disease. Treatment: General measures: bed rest (especially important in patients with carditis) Antibiotics: to eradicate GAS Symptomatic treatment: of fever, arthritis and cardiac affection. Damage to the cardiac valves: interventional measures may be considered at least one year after the acute inflammatory phase.  Prevention: Rheumatic fever is preventable if the patient is treated within the first 10 days following onset of acute pharyngitis. Prolonged (least 5 years) prophylactic antibiotic therapy (by beta lactams or macrolides) is indicated after an episode of rheumatic fever to reduce the risk of subsequent episodes if the patient is again infected with S. pyogenes. MCQ: 1-which one of the following tests can diagnose prior infection with GAS in patients with acute rheumatic fever by? 1. Blood culture. 2. Culture of a heart valve in a patient with carditis. 3. A high titer of antibody against the hyaluronic acid capsule. 4. A high titer of antibody against streptolysin O. 2-Which one of the following organisms causes tonsillopharyngitis, which may later be complicated by acute rheumatic fever? 1. Staphylococcus aureus 2. Group A β-hemolytic streptococcus 3. Group B streptococcus 4. Enterococcus 3-Which one of the following is not a clinical feature of acute rheumatic fever? 1. Migratory arthritis 2. Carditis 3. Sydenham’s chorea 4. Painful skin rash 4-which one of the following describes acute rheumatic fever? 1. Direct tissue damage by the bacteria is responsible for the development of acute rheumatic fever 2. Genetic predisposition is required for the development of acute rheumatic fever 3. It is common in females 4. Immune mediated damage is the most widely accepted theory for the pathogenesis of acute rheumatic fever 5-Which of the following is the antibody formed against Group A β-hemolytic streptococcus (GAS) that may cross react with the heart myosin and cause rheumatic fever? 1. Protein A 2. M protein 3. The capsule 4. None of the above Complete: 1. The most commonly accepted mechanism of rheumatic fever is ……………. 2. The main cause of rheumatic fever is type ………. Hypersensitivity reaction Dr/ Rasha Mokhtar Abdelkareem Lecturer Of Pathology Faculty Of Medicine  After the lecture, students should be able to: I. Define rheumatic fever and discuss its etiology, pathogenesis, pathology and complications. II. Enumerate pathological types of pericarditis and its causes. Outline the clinical features and complications of pericarditis. III. Outline the main types of endocarditis. Summarize the clinical features, pathogenesis and appearance of vegetation in each of these types. IV. Define myocarditis and cardiomyopathy and enumerate their types.   ANATOMY AND PHYSIOLOGY OF THE HEART  Muscular pump that ejects blood into the vascular tree with sufficient pressure to maintain optimal circulation.  Divided into four chambers: a right and a left atrium both lying superiorly, a right and a left ventricle both lying inferiorly and are larger.  The blood in the heart chambers moves in a carefully prescribed pathway:  venous blood from systemic circulation → right atrium → right ventricle → pulmonary arteries → lungs → pulmonary veins → left atrium → left ventricle → aorta → systemic arterial supply  Definition: an auto-immune collagen disease characterized by inflammatory changes in the fibrous tissue of different body organs specially the heart, joints, subcutaneous tissue, blood vessels, and CNS.  Incidence:  Common in children and young adults, between 5-15 years.  Girls are affected more than boys.  There is a strong individual predisposition.  Its incidence has declined in the developed countries as a result of improved living conditions and early use of antibiotics in streptococcal infection  But it is still common in the developing countries of the world.  Predisposing factors:  Overcrowding,  damp weather,  poor housing and low socioeconomic conditions. These factors predispose to upper respiratory tract infections with subsequent development of RF.  Etiology:  RF is a febrile illness follows a streptococcal pharyngitis and/or tonsillitis caused by group A of ß- hemolytic streptococci.  Develops after a latent period of 2-4 weeks (after recovery from infection).  Only a small number of patients with streptococcal infection develop an attack of RF.  The bacteria are neither found in the lesions nor in the blood stream.  RF tends to recur after subsequent attacks of streptococcal pharyngitis.  Treatment of streptococcal pharyngitis does not abolish the risk of subsequent RF.  Long term administration of penicillin prevents further attacks of streptococcal pharyngitis and of subsequent RF.  Pathogenesis  Systemic disease affecting the connective tissue around arterioles.  Streptococci pyogenes and myocardium shares common antigens.  When a susceptible host becomes infected with group A Streptococcus, autoantibodies against the bacteria are produced, triggering an autoimmune response.  These autoantibodies cause damage to human tissues due to cross-reactivity between epitopes in the components of bacteria and the host.  Molecularmimicry and cross-reactivity between streptococcal M protein in particular and the human molecules forms the basis of autoimmune damage to human target tissues in RHD i.e. cardiac muscle, valves, joints, skin, neurons etc. Rheumatic fever  MORPHOLOGIC FEATURES A. Cardiac Lesions  RHEUMATIC PANCARDITIS  Although all the three layers of the heart are affected in RF, the intensity of their involvement is variable.  1. Pericarditis:  Grossly,  there is loss of normal shiny pericardial surface due to deposition of fibrin  Milk spots white fibrotic areas  bread and butter appearance: the parietal pericardium is pulled off from the visceral pericardium, the two separated surfaces are shaggy due to thick fibrin covering them. Microscopically, fibrin is identified on the surfaces. The subserosal connective tissue is infiltrated by lymphocytes, plasma cells, histiocytes and a few neutrophils.  2. Myocarditis:  Grossly,  in the early (acute) stage, the myocardium, especially of the left ventricle, is soft and flabby.  In the intermediate stage, the interstitial tissue of the myocardium shows small foci of necrosis.  Later, tiny pale foci of the Aschoff bodies may be visible throughout the myocardium.  The Aschoff bodies are spheroidal or fusiform distinct tiny structures, 1-2 mm in size, occurring in the interstitium of the heart in RF and may be visible to naked eye.  Microscopically  The collagen fibres swell and fragment resembling a mass of fibrin (Fibrinoid degeneration or necrosis).  Inflammatory reaction forms around the foci of fibrinoid degeneration.  The reaction consists of lymphocytes. macrophages and occasional plasma cells and Aschoff' s cells (modified cardiac histiocytes, have abundant amphophilic cytoplasm and central round or ovoid nuclei). Some of the cells are large and multinucleated so called Aschoff's giant cells.  Old lesions heal by fibrosis in months to years.  3. Endocarditis:  Mural lesion:  Aschoff's nodules develop mainly on the posterior wall of the left atrium. Healing of the lesion by fibrosis ends in a white fibrous patch called "MacCallum's patch".  Valvular lesion:  Acute rheumatic valvulitis affects mainly the mitral and aortic valves.  The pathological changes are as follows: The cusps are swollen due to inflammatory edema and show infiltration by histiocytes, lymphocytes and plasma cells. The endothelium at the line of contact of the inflamed cusps undergoes degeneration and necrosis due to the sustained trauma at every heart beat.  On the rough surface multiple, firm, adherent, small vegetations 1-3 mm in diameter form. They develop on the atrial surface of the mitral and tricuspid valves and on the ventricular surface of the aortic and pulmonary valves.  The vegetations also form over the cordae tendinae and the posterior wall of the left atrium.  The vegetations undergo organization and the inflamed cusps heal by fibrosis. location of vegetations in rheumatic endocarditis  The cusps appear fibrotic, thick, irregular and may show calcified patches (chronic rheumatic valvulitis).  The cordae tendinae are fibrosed, thick and short.  Microscopically o the cusps show abnormal vascularization, fibrosis, hyalinosis and sometimes calcification.  If the cusps adhere together during the acute inflammatory stage, healing results in stenosis of the valve.  If no adhesions occur the cusps retract during healing causing incompetence of the valve  Inchronic RF both the mitral and aortic valves are affected in 50% of cases, and the mitral valve alone in about 25% of cases.  The mitral, aortic and tricuspid valves are involved in about 15% of cases, while involvement of all 4 valves or of the aortic valve alone is rare.  Thevalves of the right side of the heart are never affected alone.  Joints:  Fleeting arthritis; one joint is affected after the other, occurs specially in large joints.  Joint cavity shows serous exudate; joint effusion.  Synovial, capsular and pericapsular tissues (tendons and their sheaths) show congestion, edema, cellular infiltrate of histiocytes, lymphocytes, plasma cells and scanty Aschoff bodies.  Articular cartilage is not affected, so with resolution of inflammation complete restoration of the joint functions occur.  Subcutaneous nodules: 1. It develops over bony prominences or tendons of the arms and legs, elbow, wrist, spine, occipital protuberance in severe cases. 2. The nodules are between 1 and 2 cm in diameter, painless and resemble enlarged Aschoff bodies.  Erythematous skin rashes may occur; “erythema marginatum”. It is a long-lasting reddish rash that begins on the trunk or arms as macules, which spread outward and clear in the middle to form rings, which continue to spread and coalesce with other rings  Brain:  Edema, thrombosis, hemorrhage and perivascular round cell infiltration occur in the basal ganglia and cerebral cortex, causes sudden, involuntary, irregular, purposeless, rapid movements particularly of the extremities called “Sydenham's chorea” with muscular in-coordination and weakness. A. Major criteria: B. Minor criteria: 1. Carditis 1. Fever 2. Polyarthritis 2. Arthralgia 3. Chorea (Sydenham’s chorea) 3. Previous history of RF 4. Erythema marginatum 4. Laboratory findings of 5. Subcutaneous nodules elevated ESR, raised C-reactive protein, and leucocytosis 5. ECG finding of prolonged PR interval. Complication of rheumatic fever :  Repeated attacks cause damage to the heart in the form of: 1. valvular stenosis or incompetence, 2. myocardial fibrosis 3. pericardial adhesions ending in congestive heart failure. 4. Subacute infective endocarditis may complicate chronic rheumatic valvulitis.  The most serious effect is rheumatic myocarditis → various degrees of acute HF.  Causes of death: A. Heart failure: from active carditis or secondary to chronic rheumatic valvulitis. B. Embolic manifestation: from atrial or vascular thrombosis. It causes death in 20-35% of cases. C. Bacterial endocarditis: causes death in 10-15% of cases. D. Pneumonia: in congested lungs.  Def: inflammation of pericardium  Types: 1. Fibrinous (Serofibrinous) Pericarditis 2. Suppurative Pericarditis  Fibrinous (Serofibrinous) Pericarditis: Caused by the following diseases: 1. Rheumatic fever is the commonest cause. 2. Complicates lobar pneumonia and bronchopneumonia. 3. Tuberculous pericarditis. 4. Over myocardial infarction. 6. A terminal complication in uraemia and diabetes mellitus.  Suppurative Pericarditis: Is caused by: (1) Streptococcus, staphylococcus, and meningococcus septicaemia. (2) Blood and lymphatic spread from pneumococcal infection of the lung. (3) Direct spread from empyema, osteomyelitis of the ribs, sub-phrenic abscess or liver abscess. (4) Penetrating chest wounds.  Pathological features: Suppurative inflammation with pus accumulation in the pericardial sac.  Complication:  If the patient survives, the lesion heals by organization causing pericardial adhesions, constrictive pericarditis or adherent mediastino- pericarditis. Adherent Mediastino-pericarditis: Fibrous adhesions between the parietal pericardium and adjacent mediastinal structures, pleura, diaphragm and thoracic cage. Constrictive Pericarditis: Dense adhesions between the two layers; of the pericardium with partial or complete obliteration of the pericardial sac.  The lesion limits the diastolic expansion of the heart and constricts the orifice of the venae cava causing chronic general venous congestion.  TYPES OF ENDOCRADITIS 1. INFECTIVE 2. Non-Infective ENDOCARDITIS Endocarditis: a. Acute infective endocarditis (AIE or ABE). a. Rheumatic endocarditis. b. Atypical verrucous endocarditis (Libman-Sacks b. Subacute infective endocarditis). endocarditis (SIE or SBE). c. Non infective thrombotic endocarditis (Terminal endocarditis)  Aetiology: Causative organisms: Virulent bacteria e.g. streptococcus haemolyticus, staphylococcus aureus, pneumococci and gonococci.  Pathogenesis:  Acute infective endocarditis is a part of a septicaemia.  The source of bacteria is a septic focus in the body as puerperal sepsis, acute Osteomyelitis, carbuncle, pneumonia.  Bacteria reach the heart by the blood stream and attack the healthy valve.  Pathological features: (1) The valves commonly affected are the mitral and aortic. (2) The affected valve shows suppurative inflammation with ulceration and perforation of the cusps. (3) Bulky septic vegetations develop on the surfaces of the inflamed cusps, cordae tendinae and mural endocardium. They are friable and yellow in color.  The vegetations consist of fibrin, platelets, bacterial colonies and acute inflammatory cells in the form of polymorphonuclear leucocytes and pus cells. (4) Fragmentation of the vegetations gives rise to septic emboli which cause pyaemic abscesses.  The disease terminates by death in 1-2 month due to the resulting valve incompetence and the severe bacterial infection  Aetiology: Causative organisms: It is caused by bacteria relatively of low virulence. The most important is “viridans” group of α- hemolytic streptococci. Rarely haemophilus influenza, E. coli and other bacteria.  Pathogenesis: The organisms enter the blood stream from dental sepsis and throat infections during mastication, dental extraction and tonsillectomy (Bacteraemia). They invade valves predisposed to infection by: (a) Chronic rheumatic valvulitis. (b) Congenital malformations as bicuspid aortic valve, pulmonary stenosis, septal defects... etc.   Pathological Lesions: I. Cardiac Lesions: (1) Vegetations develop mainly on the mitral and aortic valves as they are the valves commonly affected by rheumatic valvulitis. The vegetations are bulky, polypoid, friable and easily detached. They are grey, reddish or brown in color. Vegetations develop on any surface of the cusps, cordae tendinae and may extend over the posterior wall of the left atrium over the MacCallum’s patch. Microscopically: the vegetations show: (a) A top layer of platelets and fibrin covering colonies of bacteria. (b) A base of granulation tissue infiltrated by macrophages, further down it changes into fibrous tissue which blends with the cusp substance. (2) The myocardium shows cloudy swelling and fatty degeneration due to toxaemia. Endocarditis of the mitral valve (subacute, caused by Streptococcus viridens). vegetations are denoted by arrows.  II. Embolic Lesions: Vegetations fragment and form emboli causing: (1) Infarcts: In the spleen, kidney and brain. (2) Retinal necrosis and blindness: Due to embolism in the retinal artery. (3) Coronary artery embolism: Rare. (4) Mycotic aneurysms: Occur commonly in the cerebral and mesenteric arteries, rarely elsewhere.  III. Toxic Lesions: (1) Fever, anaemia, leucocytosis and clubbing of the fingers. (2) Degeneration in the liver and kidney and enlargement of the spleen. Course: (1) Termination in congestive heart failure within 6-18 months. (2) With antibiotics the vegetations undergo organization, fibrosis, calcification. Disturbance in the valvular function may cause failure. FEATURE Acute bacterial endocarditis. Subacute bacterial endocarditis. 1. Duration 6 weeks 2. Most common Staph. aureus, Streptococcus organisms b-streptococci viridans 3. Virulence of Highly virulent Less virulent organisms 4. Previous condition Usually previously Usually previously of valves normal damaged 5. Lesion on valves Invasive, destructive, Usually not invasive suppurative or suppurative 6. Clinical features Features of acute Splenomegaly, systemic infection clubbing of fingers, Petechiae  Atypicalverrucous endocarditis is a manifestation of collagen diseases. Vegetations are small, granular and multiple. Œ Non-bacterial thrombotic endocarditis is an involvement of the heart valves by sterile thrombotic vegetations, often preceded by hypercoagulable state.  Definition: It is an inflammation of the myocardium, which occurs as a result of: a) Direct involvement by the causal agents. b) Toxin-mediated injury. c) A local hypersensitivity reaction.  The commonest causes are viral.  Types: 1. Viral interstitial myocarditis 2. Suppurative myocarditis 3. Toxic myocarditis 4. Hypersensitivity reactions 5. Granulomatous myocarditis  A heterogenous group of disorders, in which there is chronic myocardial dysfunction of uncertain cause.  Cardiomyopathy is classified as hypertrophic, dilated and restrictive.  They may be further divided into:  primary types of unknown etiology, and confined to the myocardium  secondary types which occur with some systemic disorders.