1. Dr. M. A. SOFI MD; FRCP (London); FRCPEdin; FRCSEdin

2. Signs and symptoms  Fever possibly low- grade and intermittent 90%.  Heart murmurs 85%  Petechiae: Common, but nonspecific, finding  Subungual (splinter) hemorrhages: Dark- red, linear lesions in the nail beds  Osler nodes: Tender subcutaneous nodules usually found on the distal pads of the digits  Janeway lesions: Non-tender maculae on the palms and soles  Roth spots: Retinal hemorrhages with small, clear centers; rare Definition: Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium, or a septal defect

3.  Splenomegaly  Stiff neck  Delirium  Paralysis, hemiparesis, aphasia  Conjunctival hemorrhage  Pallor  Gallops  Rales  Cardiac arrhythmia  Pericardial rub  Pleural friction rub Other signs of IE include the following

4. Petechiae Janeway lesions

5. Osler node Splinter hemorrhage

6.  Low-grade fever: Absent in 3-15% of patients  Anorexia  Weight loss  Influenza-like syndromes  Polymyalgia-like syndromes  Pleuritic pain  Syndromes similar to rheumatic fever, such as fever, dulled sensorium (as in typhoid), headaches  Abdominal symptoms, such as right upper quadrant pain, vomiting, postprandial distress, appendicitis-like symptoms Subacute native valve endocarditis The symptoms of early subacute native valve endocarditis (NVE) are usually subtle and nonspecific; they include the following:

7. Blood culture criteria for IE:  Two blood cultures positive for organisms typically found in patients with IE  Blood cultures persistently positive for one of these organisms, from cultures drawn more than 12 hours apart  Three or more separate blood cultures drawn at least 1 hour apart Echocardiographic criteria for IE  Oscillating intracardiac mass on a valve or on supporting structures, in the path of regurgitant jets, or on implanted material.  Myocardial abscess  Development of partial dehiscence of a prosthetic valve  New-onset valvular regurgitation Diagnosis The Duke diagnostic criteria, developed by Durack and colleagues, are generally used to make a definitive diagnosis of IE. The criteria combine the clinical, microbiologic, pathologic, and echocardiographic characteristics of a specific case

8.  Predisposing heart condition or intravenous drug use  Fever of 38°C or higher  Vascular phenomenon:  Major arterial emboli  Septic pulmonary infarcts  Mycotic aneurysm  Intracranial hemorrhage  Conjunctival hemorrhage  Janeway lesions  Immunologic phenomenon:  Glomerulonephritis  Osler nodes  Roth spots  Rheumatoid factor  Positive blood culture results not meeting major criteria or serologic evidence of active infection with an organism consistent with IE  Echocardiogram results consistent with IE but not meeting major echocardiographic criteria A definitive clinical diagnosis can be made based on the following:  2 major criteria  1 major criterion and 3 minor criteria  5 minor criteria Minor criteria for IE include the following:

9.  RHD (30% of NVE) - Primarily involves the mitral valve followed by the aortic valve  Congenital heart disease (15% of NVE) - Underlying etiologies include:  Patent ductus arteriosus  Ventricular septal defect  Tetralogy of Fallot  Native or surgical high-flow lesion.  Mitral valve prolapse with an associated murmur (20% of NVE) Degenerative heart disease:  Calcific aortic stenosis due to a bicuspid valve  Marfan syndrome  Syphilitic disease Native valve endocarditis: Main underlying causes of NVE Approximately 70% of infections in NVE are caused by Streptococcus species, including S viridans, Streptococcus bovis, and enterococci. Staphylococcus species cause 25% of cases and generally demonstrate a more aggressive acute course.

10. Infection associated with aortic valve prostheses is particularly associated with  local abscess and fistula formation  Valvular dehiscence. This may lead to:  Shock  Heart failure  Heart block  Shunting of blood to the right atrium  Pericardial tamponade  Peripheral emboli to the central nervous system and elsewhere. Early PVE may be caused by a variety of pathogens, including:  S aureus and S epidermidis. These nosocomially acquired organisms are often methicillin-resistant (eg, MRSA).  Late disease is most commonly caused by streptococci.  Overall, CoNS are the most frequent cause of PVE (30%). Prosthetic valve endocarditis Early PVE, which presents shortly after surgery, has a different bacteriology and prognosis than late PVE, which presents in a subacute fashion similar to NVE.

11. Diagnosis of endocarditis in IV drug users can be difficult and requires a high index of suspicion.  2/3 of patients have no previous history of heart disease or murmur on admission.  A murmur may be absent in those with tricuspid disease.  Pulmonary manifestations may be prominent in patients with tricuspid infection:  1/3 have pleuritic chest pain, and three quarters demonstrate chest radiographic abnormalities.  S aureus is the most common (< 50% of cases) etiologic organism in patients with IVDA IE.  MRSA accounts for an increasing portion of S aureus infections and has been associated with previous hospitalizations, long-term addiction, and non-prescribed antibiotic use.  Groups A, C, and G streptococci and enterococci are also recovered from patients with IVDA IE. IVDA infective endocarditis

12. Endocarditis may be associated with:  Central or peripheral IV catheters  Pacemakers and defibrillators  Hemodialysis shunts  Hyperalimentation lines  These patients tend to have significant comorbidities, more advanced age, and predominant infection with S aureus.  The mortality rate is high in this group. The organisms that cause NIE/HCIE obviously are related to the type of underlying bacteremia. The gram- positive cocci (ie, S aureus, CoNS, enterococci, nonenterococcal streptococci) are the most common pathogens. Fungal endocarditis is found in IV drug users and ICU patients who receive broad-spectrum antibiotics. Blood cultures are often negative, and diagnosis frequently is made after microscopic examination of large emboli. Nosocomial/healthcare-associated infective endocarditis

13. Causative Organism(s) Clinical Features of IE Staphylococcus aureus Overall, S aureus infection is the most common cause of IE, including PVE, acute IE, and IVDA IE. Approximately 35-60.5% of staphylococcal bacteremias are complicated by IE. More than half the cases are not associated with underlying valvular disease. The mortality rate of S aureus IE is 40-50%. S aureus infection is the second most common cause of nosocomial BSIs, second only to CoNS infection. The incidence of MRSA infections, both the hospital- and community-acquired varieties, has dramatically increased (50% of isolates) The primary risk factor for S aureus BSI is the presence of intravascular lines. Other risk factors include cancer, diabetes, corticosteroid use, IVDA, alcoholism, and renal failure. Clinical features associated with different pathogens Clinical Features of Infective Endocarditis According to Causative Organism

14. Causative Organism(s) Clinical Features of IE Streptococcus viridans This organism accounts for approximately 50-60% of cases of subacute disease. Most clinical signs and symptoms are mediated immunologically. Streptococcus intermedius group These infections may be acute or subacute. S intermedius infection accounts for 15% of streptococcal IE cases. Members of the S intermedius group, especially S anginosus, are unique among the streptococci in that they can actively invade tissue and form abscesses, often in the CNS. AbiotrophiaApproximately 5% of subacute cases of IE are due to infection with Abiotrophia species. They require metabolically active forms of vitamin B-6 for growth. This type of IE is associated with large vegetations that lead to embolization and a high rate of posttreatment relapse. Clinical features associated with different pathogens Clinical Features of Infective Endocarditis According to Causative Organism

15. Causative Organism(s) Clinical Features of IE Group D streptococci Most cases are subacute. The source is the gastrointestinal or genitourinary tract. It is the third most common cause of IE. They pose major resistance problems for antibiotics. Nonenterococcal group D The clinical course is subacute. Infection often reflects underlying abnormalities of the large bowel (eg, ulcerative colitis, polyps, cancer). The organisms are sensitive to penicillin. Group B streptococci Acute disease develops in pregnant patients and older patients with underlying diseases (eg, cancer, diabetes, alcoholism). The mortality rate is 40%. Complications include metastatic infection, arterial thrombi, and congestive heart failure. It often requires valve replacement for cure. Clinical features associated with different pathogens Clinical Features of Infective Endocarditis According to Causative Organism

16. Causative Organism(s) Clinical Features of IE Group A, C, and G streptococci Acute disease resembles that of S aureus IE (30-70% mortality rate), with suppurative complications. Group A organisms respond to penicillin alone. Group C and G organisms require a combination of synergistic antibiotics (as with enterococci). Coagulase- negative S aureus This causes subacute disease. It behaves similarly to S viridans infection. It accounts for approximately 30% of PVE cases and less than 5% of NVE cases. [21] Pseudomonas aeruginosa This is usually acute, except when it involves the right side of the heart in IVDA IE. Surgery is commonly required for cure. Clinical features associated with different pathogens Clinical Features of Infective Endocarditis According to Causative Organism

17. Causative Organism(s) Clinical Features of IE HACEK (ie, Haemophilus aphrophilus, Actinobacillus actinomycetemcom itans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) These organisms usually cause subacute disease. They account for approximately 5% of IE cases. They are the most common gram-negative organisms isolated from patients with IE. Complications may include massive arterial emboli and congestive heart failure. Cure requires ampicillin, gentamicin, and surgery. FungalThese usually cause subacute disease. The most common organism of both fungal NVE and fungal PVE is Candida albicans. Fungal IVDA IE is usually caused by Candida parapsilosis or Candida tropicalis. Aspergillus species are observed in fungal PVE and NIE. BartonellaThe most commonly involved species is Bartonella quintana. IE typically develops in homeless males who have extremely substandard hygiene. Bartonella must be considered in cases of culture-negative endocarditis among homeless individuals Clinical features associated with different pathogens Clinical Features of Infective Endocarditis According to Causative Organism

18.  Thrombotic nonbacterial endocarditis  Vasculitis  Temporal arteritis  Marantic endocarditis  Connective tissue disease  Fever of unknown origin (FUO)  Intra-abdominal infections  Septic pulmonary infarction  Tricuspid regurgitation  Antiphospholipid Syndrome  Atrial Myxoma  Cardiac Neoplasms, Primary  Endocarditis  Lyme Disease  Polymyalgia Rheumatica  Reactive Arthritis  Systemic Lupus Erythematosus Differential Diagnoses

19.  25% of S aureus bloodstream infections (BSIs) represent IE or metastatic infections  S aureus to produce an endotheliosis, the presence of a continuous bacteremia does not necessarily imply an infected valvular vegetation  Clue to continuous bacteremia/IE is the presence of S aureus bacteriuria associated with hematuria  25% of patients with staphylococcal bacteremia and 23% of those with catheters as the primary focus have evidence of IE based on transesophageal echocardiography (TEE) findings, in the absence of clinical and transthoracic echocardiography (TTE) findings.  CBC (Leukocytosis in acute stage)  ESR (Elevated in 90%)  BUN  Coagulation Profile  RF (+50%)  Proteinuria  Hematuria 50%  3-5 sets of blood cultures over 24 hours  3 sets may be drawn over 30 minutes (with separate venipunctures)  Culture-negative infective endocarditis  Vasculitis  Prior antibiotic therapy  Fungal infections  Atypical organisms Diagnostic work up : The criterion standard test for diagnosing infective endocarditis (IE) is the documentation of a continuous bacteremia (>30 min in duration) based on blood culture results

20.  TTE sensitivity of approximately 60% for identification of valvular lesions in patients with NVE.  TTE has a sensitivity of 20% in patients with PVE.  The sensitivity of TEE in detecting the vegetations of NVE is 90-100%.  In patients with PVE, the sensitivity of TEE is greater than 90%.  TEE successfully visualizes vegetations of the tricuspid valve in more than 90% of cases of pacemaker IE, compared with less than the 50% achieved by TTE.  Echocardiography is useful for predicting the potential complications of IE, especially those that are embolic in nature  Echocardiographic predictors of systemic embolization in patients with IE are the following ◦ Large valvular vegetations (>10 mm in diameter) ◦ Multiple vegetations ◦ Mobile but pedunculated vegetations ◦ Prolapsing vegetations  Echocardiography is also highly useful for detecting abscesses Echocardiography: Echocardiography has become the indirect diagnostic method of choice. The diagnosis of IE can never be excluded based on negative echocardiogram findings, either from TTE or from TEE.

21. The major goals of therapy for infective endocarditis (IE) are: 1. Eradicate the infectious agent from the thrombus 2. Intra cardiac and extra cardiac consequences of IE. 3. Surgical intervention. 4. Emergency care: Correct diagnosis & stabilization General Measures:  Treatment of congestive heart failure  Oxygen  Hemodialysis (may be required in patients with RF)  Empiric antibiotic therapy is chosen based on the most likely infecting organisms. Treatment

22.  Native valve endocarditis (NVE): Penicillin G wih gentamicin for synergistic coverage of streptococci  Patients with IVdrug use have been treated with nafcillin and gentamicin to cover for methicillin-sensitive staphylococci.  Prosthetic valve endocarditis (PVE) may be caused by MRSA or coagulase- negative staphylococci (CoNS)  Culture-negative NVE is usually treated with vancomycin and gentamicin  Patients with culture- negative PVE are usually given vancomycin and gentamicin, targeting enterococcal or CoNS infections Treatment

23.  CHF refractory to standard medical therapy  Fungal IE (except that caused by Histoplasma capsulatum)  Persistent sepsis after 72 hours of appropriate antibiotic Rx  Recurrent septic emboli, especially after 2 weeks of antibiotic treatment  Rupture of an aneurysm of the sinus of Valsalva  Conduction disturbances caused by a septal abscess  Kissing infection of the anterior mitral leaflet in patients with IE of the aortic valve  Paravalvular abscess and intracardiac fistula almost always require surgical intervention Approximately 15-25% of patients with IE eventually require surgery. Indications for surgical intervention in patients with NVE are as follows:

24. Patients at higher risk include:  Presence of prosthetic heart valve  History of endocarditis  Cardiac transplant recipients who develop cardiac valvulopathy  Congenital heart disease with a high- pressure gradient lesion Also consider prophylaxis in procedures involving:  Manipulation of gingival tissue or the periapical region of teeth, or perforation of the oral mucosa  Incision in the respiratory mucosa  Infected skin or musculoskeletal tissue including incision and drainage of an abscess  Prophylaxis is no longer routinely recommended for GI procedures. Prevention of Infective Endocarditis: 15-25% cases of IE are due to procedures that produce bacteremia