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

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.

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

Patients with IE may have involvement of other organs: Metastatic infection (eg, vertebral osteomyelitis), Embolic events (eg, focal neurologic deficits, renal infarct, splenic infarct). Systemic immune reaction (eg, glomerulonephritis). In right-sided endocarditis, septic pulmonary emboli may be seen Chest radiograph of a patient with tricuspid valve endocarditis due to S. aureus Multiple cavitating lung nodules due to septic pulmonary emboli.

Petechiae Janeway lesions

Osler node Splinter hemorrhage

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, dull sensorium, headaches Abdominal symptoms, such as right upper quadrant pain, vomiting, postprandial distress, appendicitis-like symptoms Native valve endocarditis The symptoms of early subacute native valve endocarditis (NVE) are usually subtle and nonspecific; they include the following:

Blood culture criteria for IE: Typical microorganism for infective endocarditis from two separate blood cultures 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, are generally used to make a definitive diagnosis of IE. The criteria combine the clinical, microbiologic, pathologic, and echocardiographic characteristics of a specific case

 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:

 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.

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 rt. 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.

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

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

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

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. 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

CBC (Leukocytosis in acute stage) ESR (Elevated in 90%) BUN Coagulation Profile RF (+50%) Proteinuria Hematuria 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

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 %. 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.

Class I - There is evidence and/or general agreement that TTE or TEE should be performed in patients with native or prosthetic valve IE. Class IIa - The weight of evidence or opinion is in favor of the usefulness of TTE or TEE in patients with native or prosthetic valve IE. Class IIb - The weight of evidence or opinion is less well-established for the usefulness of TTE or TEE in patients with native or prosthetic valve IE. CT: computed tomography; IE: infective endocarditis; NVE: native valve endocarditis; PVE: prosthetic valve endocarditis; TEE: transesophageal echocardiography; TTE: transthoracic echocardiography. * Repeat TEE and/or TTE recommended for re-evaluation of patients with IE and a change in clinical signs or symptoms and in patients at high risk of complications.

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

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

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:

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