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Zoltán Péterfi 1st Department of Internal Medicine, Dep. Infectology Pécs Definition Infectious Endocarditis (IE): an infection of the heart’s endocardial surface Classified into four groups: Native Valve IE Prosthetic Valve IE Intravenous drug abuse (IVDA) IE Nosocomial IE Further Classification Acute Affects normal heart valves Rapidly destructive Metastatic foci Commonly Staphylococcus If not treated, usually fatal within 6 weeks Subacute Often affects damaged heart valves Indolent nature If not treated, usually fatal by one year Infective Endocarditis Febrile illness Persistent bacteremia Characteristic lesion of microbial infection of the endothelial surface of the heart the vegetation Variable in size Amorphous mass of fibrin & platelets Abundant organisms Few inflammatory cells Pathophysiology Turbulent blood flow disrupts the endocardium making it “sticky” Bacteremia delivers the organisms to the endocardial surface Adherence of the organisms to the endocardial surface Eventual invasion of the valvular leaflets Pathophysiology Clinical manifestations Direct ○ Constitutional symptoms of infection (cytokine) Indirect ○ Local destructive effects of infection ○ Embolization – septic or bland ○ Hematogenous seeding of infection - N.B. may present as local infection or persistent fever, metastatic abscesses may be small, miliary ○ Immune response - Immune complex or complement-mediated Infective Endocarditis Nonbacterial Thrombotic Endocarditis Platelet-fibrin thrombi - Endothelial injury - Hypercoagulable state Lesions seen at coaptation points of valves ○ Atrial surface mitral/tricuspid ○ Ventricular surface aortic/pulmonic Modes of endothelial injury ○ High velocity jet ○ Flow from high pressure to low pressure chamber ○ Flow across narrow orifice of high velocity Bacteria deposited on edges of low pressure sink or site of jet impaction Venturi Effect Epidemiology Incidence difficult to ascertain and varies according to location Much more common in males than in females May occur in persons of any age and increasingly common in elderly Mortality ranges from 20-30% Risk Factors Intravenous drug abuse Artificial heart valves and pacemakers Acquired heart defects Calcific aortic stenosis Mitral valve prolapse with regurgitation Congenital heart defects Intravascular catheters Infecting Organisms Common bacteria S. aureus Streptococci Enterococci Not so common bacteria Fungi Pseudomonas HACEK Infective Endocarditis Gram negative organisms P. aeruginosa most common HACEK - slow growing, fastidious organisms that may need 3 weeks to grow out of culture ○ Haemophilus sp. ○ Actinobacillus ○ Cardiobacterium ○ Eikenella ○ Kingella Symptoms Acute High grade fever and chills Shortness of breath Arthralgias/ myalgias Abdominal pain Pleuritic chest pain Back pain Subacute Low grade fever Anorexia Weight loss Fatigue Arthralgias/ myalgias Abdominal pain N/V The onset of symptoms is usually ~2 weeks or less from the initiating bacteremia Signs Fever Heart murmur Nonspecific signs – petechiae, subungal or “splinter” hemorrhages, clubbing, splenomegaly, neurologic changes More specific signs - Osler’s Nodes, Janeway lesions, and Roth Spots Petechiae 1. Nonspecific 2. Often located on extremities or mucous membranes dermatology.about.com/.../ blpetechiaephoto.htm medicine.ucsd.edu/clinicalimg/ Eye-Petechiae.html www.lib.uiowa.edu/ hardin/ md/cdc/3184.html Splinter Hemorrhages 1. Nonspecific 2. Nonblanching 3. Linear reddish-brown lesions found under the nail bed 4. Usually do NOT extend the entire length of the nail Osler’s Nodes 1. More specific 2. Painful and erythematous nodules 3. Located on pulp of fingers and toes 4. More common in subacute IE Janeway Lesions 1. More specific 2. Erythematous, blanching macules 3. Nonpainful 4. Located on palms and soles Roth’s Spots The Essential Blood Test Blood Cultures Minimum of three blood cultures Three separate venipuncture sites Obtain 10-20mL in adults and 0.5-5mL in children Positive Result Typical organisms present in at least 2 separate samples Persistently positive blood culture (atypical organisms) ○ Two positive blood cultures obtained at least 12 hours apart ○ Three or a more positive blood cultures in which the first and last samples were collected at least one hour apart Additional Labs CBC ESR and CRP Complement levels (C3, C4, CH50) RF Urinalysis Baseline chemistries and coags Imaging Chest x-ray Look for multiple focal infiltrates and calcification of heart valves EKG Rarely diagnostic Look for evidence of ischemia, conduction delay, and arrhythmias Echocardiography Indications for Echocardiography Transthoracic echocardiography (TTE) First line if suspected IE Native valves Transesophageal echocardiography (TEE) Prosthetic valves Intracardiac complications Inadequate TTE Fungal or S. aureus or bacteremia ECHOCARDIOGRAPHY MAJOR findings: Vegetation Abscess Paraprosthetic dehiscent minor findings: Fenestration Fistula Pseudoaneurysm Rupture (tendon, valve) TTE NVIE PVIE TEE NVIE PVIE sensitivity specificity 50% 78% sensitivity specificity 100% 89% 17% 94% 83% 95% 23 24 Making the Diagnosis Pelletier and Petersdorf criteria (1977) Classification scheme of definite, probable, and possible IE Reasonably specific but lacked sensitivity Von Reyn criteria (1981) Added “rejected” as a category Added more clinical criteria Improved specificity and clinical utility Duke criteria (1994) Included the role of echocardiography in diagnosis Added IVDA as a “predisposing heart condition” Modified Duke Criteria Definite IE Microorganism (via culture or histology) in a valvular vegetation, embolized vegetation, or intracardiac abscess Histologic evidence of vegetation or intracardiac abscess Possible IE 2 major 1 major and 3 minor 5 minor Rejected IE Resolution of illness with four days or less of antibiotics Treatment Parenteral antibiotics High serum concentrations to penetrate vegetations Prolonged treatment to kill dormant bacteria clustered in vegetations Surgery Intracardiac complications Surveillance blood cultures Antibiotic therapy Streptococci (alfa haemolytic): Penicillin susceptible viridans or S. bovis (MIC<1 mg/l) ○ penicillin or ceftriaxon 4 weeks ○ penicillin + aminoglycoside 2 weeks Intermediate susceptible streptococci (MIC >1 mg/l) ○ penicillin vagy ceftriaxon 4-6 weeks+ aminoglicoside 2 weeks ○ vancomycin/teicoplanin 4-6 weeks (beta-lactame intolerance) 28 Enterococci No bactericidic antibiotics combination!! Penicillin, aminoglicoside, vancomycin susceptible ○ penicillin G or Ampicillin + gentamycin 4-6 weeks ○ vancomycin + gentamycin 4-6 weeks Penicillin allergic, vancomycin rezistant strains ○ teicoplanin + gentamycin 4-6 weeks Penicillin rezistant (MIC> 8 mg/l) ○ vancomycin + gentamycin 4-6 weeks ○ amoxicillin/calvulanic acid + gentamycin4-6 weeks 29 Staphylococci NVIE methicillin susceptible ○ oxacillin or cefazolin + gentamycin ○ vancomycin 4-6 weeks 4-6 weeks NVIE methicillin rezistant ○ vancomycin 4-6 weeks PVIE methicillin susceptible ○ oxacillin + rifampicin + gentamycin 6 weeks PVIE methicillin rezistant ○ vancomycin + rifampicin + gentamycin 6 weeks 30 Complications Embolic Local spread of infection Metastatic spread of infection Formation of immune complexes – glomerulonephritis and arthritis Embolic Complications Occur in up to 40% of patients with IE Predictors of embolization Size of vegetation Left-sided vegetations Fungal pathogens, S. aureus, and Strep. bovis Incidence decreases significantly after initiation of effective antibiotics Embolic Complications Stroke Myocardial Infarction Fragments of valvular vegetation or vegetation-induced stenosis of coronary ostia Ischemic limbs Hypoxia from pulmonary emboli Abdominal pain (splenic or renal infarction) Septic Pulmonary Emboli Septic Retinal Embolus Local Spread of Infection Heart failure Extensive valvular damage Paravalvular abscess (30-40%) Most common in aortic valve, IVDA, and S. aureus May extend into adjacent conduction tissue causing arrythmias Higher rates of embolization and mortality Pericarditis Fistulous intracardiac connections Local Spread of Infection Acute S. aureus IE with perforation of the aortic valve and aortic valve vegetations. Acute S. aureus IE with mitral valve ring abscess extending into myocardium. Metastatic Spread of Infection Metastatic abscess Kidneys, spleen, brain, soft tissues Meningitis and/or encephalitis Vertebral osteomyelitis Septic arthritis Poor Prognostic Factors Female S. aureus Vegetation size Aortic valve Prosthetic valve Older age Diabetes mellitus Low serum albumin Apache II score Heart failure Paravalvular abscess Embolic events Prevention Prophylactic regimen targeted against likely organism Strep. viridans – oral, respiratory, eosphogeal Enterococcus – genitourinary, gastrointestinal S. aureus – infected skin, mucosal surfaces Prevention – the underlying lesion High risk lesions Intermediate risk Prosthetic valves MVP with murmur Prior IE Pure MS Cyanotic congenital heart Tricuspid disease disease PDA AR, AS, MR,MS with MR VSD Coarctation Surgical systemicpulmonary shunts Lesions at highest risk Pulmonary stenosis ASH Bicuspid Ao valve with no hemodynamic significance Chemoprophylaxis Adult Prophylaxis: Dental, Oral, Respiratory, Esophageal Standard Regimen Amoxicillin 2g PO 1h before procedure or Ampicillin 2g IM/IV 30m before procedure Penicillin Allergic Clindamycin 600 mg PO 1h before procedure or 600 mg IV 30m before Cephalexin OR Cefadroxil 2g PO 1 hour before Cefazolin 1.0g IM/IV 30 min before procedure Azithromycin or Clarithromycin 500mg PO 1h before Adult Genitourinary or Gastrointestinal Procedures High Risk Patients Standard Regimen Before procedure (30 minutes): Ampicillin 2g IV/IM AND Gentamicin 1.5 mg/kg (MAX 120 mg) IM/IV After procedure (6 hours later) Ampicillin 1g IM/IV OR Amoxicillin 1g PO Penicillin Allergic Complete infusion 30 minutes before procedure Vancomycin 1g IV over 1-2h AND Gentamycin 1.5 mg/kg IV/IM (MAX 120 mg) Moderate Risk Patients Standard Regimen Amoxicillin 2g PO 1h before OR Ampicillin 2g IM/IV 30m before Penicillin Allergic Vancomycin 1g IV over 1-2h, complete 30m before