INFECTIVE ENDOCARDITIS

Vegetations (arrows) due to viridans streptococcal endocarditis involving the mitral valve.
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Infective endocarditis (IE) is an infection of the endocardial surface of the heart. The intracardiac effects of this infection include severe valvular insufficiency, which may lead to congestive heart failure and myocardial abscesses. IE also produces a wide variety of systemic signs and symptoms through several mechanisms, including both sterile and infected emboli and various immunological phenomena.

INFECTIVE ENDOCARDITIS

Prevalence USA 38,0 92,9 1 000 000 Canada 20,0 25,0 1 000 000
PRIMARY 25 %* 59,9 %* SECONDARY 75 %* 40,1 %* -rheumatic valvular diseases - 20,3 % -congenital valvular disorders - 11,3 % -aterosclerotic valvular disorders 3,5 %

If left untreated, IE is generally fatal

ETIOLOGY

Organisms Causing Major Clinical Forms of Endocarditis:

Staphylococcus 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%.

ETIOLOGY

Organisms Causing Major Clinical Forms of Endocarditis:

Streptococcus viridans

This organism accounts for approximately 50-60% of cases of subacute disease. Most clinical signs and symptoms are mediated immunologically. These infections may be acute or subacute. S intermedius infection accounts for 15% of streptococcal IE cases. S intermedius is unique among the streptococci; it can actively invade tissue and can cause abscesses.

Streptococcus intermedius group

ETIOLOGY

Organisms Causing Major Clinical Forms of Endocarditis:

Nonenterococcal group D organisms

Group B streptococci

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. 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. 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).

Group A, C, and G streptococci

ETIOLOGY
Coagulase-negative S aureus

Organisms Causing Major Clinical Forms of Endocarditis:

Pseudomonas aeruginosa

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.10
This is usually acute, except when it involves the right side of the heart in IVDA IE. Surgery is commonly required for cure.

HACEK organisms (ie, Haemophilus aphrophilus, Actinobacillus

actinomycetemcomitans, 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.

ETIOLOGY

Organisms Causing Major Clinical Forms of Endocarditis:

Fungi

These 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.

Acute endocarditis usually occurs when heart valves are colonized by virulent bacteria in the course of microbemia. The most common cause of acute endocarditis is Staphylococcus aureus; other less common causes are Streptococcus

pneumoniae, Neisseria gonorrhoeae, Streptococcus pyogenes, and Enterococcus faecalis.

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Patients with subacute endocarditis usually have underlying valvular heart disease and are infected by less virulent organisms such as viridans streptococci, enterococci, nonenterococcal group D streptococci, microaerophilic streptococci, and Haemophilus species.

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Pathophysiology

All cases of IE develop from a commonly shared process, as follows: Bacteremia (nosocomial or spontaneous) that delivers the organisms to the surface of the valve Adherence of the organisms Eventual invasion of the valvular leaflets

Bacteremia can result from various invasive procedures

Endoscopy

Colonoscopy

Rate of 0-20% CoNS, streptococci, diphtheroids

Rate of 0-20%

Barium enema

Escherichia coli, Bacteroides species

Rate of 0-20% Enterococci, aerobic and anaerobic gram-negative rods
Rate of 40-100%

Dental extractions

Transurethral resection of the prostate

S viridans

Transesophageal echocardiography

Rate of 20-40% Coliforms, enterococci, S aureus

Rate of 0-20% S viridans, anaerobic organisms, streptococci

primary portals

oral cavity, skin, upper respiratory tract gastrointestinal tract genitourinary tract
The incidence of nosocomial bacteremias, mostly associated with intravascular lines, has more than doubled in the last few years. Up to 90% of bloodstream infections (BSIs) caused by these devices are secondary to the placement of various types of central venous catheters.
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primary portals

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primary portals

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PATHOGENESIS

The normal cardiac valve endothelium is resistant to colonization by bacteria; endocarditis is the result of the interaction among (1) host factors that predispose the endothelium to infection, (2) circumstances that lead to transient bacteremia, and (3) the tissue tropism and virulence of the circulating bacteria.
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PATHOPHYSIOLOGY

The clinical manifestations of IE result from:

1. Local destructive effects of intracardiac infection (distortion or perforation of valve leaflets, rupture of chordae tendineae, perforations or fistulas between major vessels and cardiac chambers, functional valvular stenosis) with congestive heart failure; 2. Embolization of fragments of the vegetation, resulting in infection or infarction including the spleen, kidney, meninges, brain, bone, pericardium, synovium; 3. The hematogenous seeding of remote sites during continuous bacteremia (hyper-gammaglobulinemia, cryoglobulins, splenomegaly); 4. Immunologic response to the infection with tissue injury due to deposition of preformed immune complexes or antibody-complement interaction with antigens deposited in tissues (glomerulonephritis, Oslers nodes, rheumatological manifestations). 17

Clinical and Laboratory Features of Infective Endocarditis

Fever 80-90 % Chills and sweats 40-75 % Anorexia, weight loss, malaise 25-50 % Myalgias, arthralgias 15-30 % Back pain 7-15 % Heart murmur 80-85 % New/worsened regurgitant murmur 10-40 %

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Clinical and Laboratory Features of Infective Endocarditis

Arterial emboli 20-50 % Splenomegaly 15-50 % Clubbing 10-20 % Neurologic manifestations 20-40 % Peripheral manifestations (Osler's nodes, subungual hemorrhages, Janeway lesions, Roth's spots) 2-15 %
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Clinical and Laboratory Features of Infective Endocarditis

Petechiae 10-40 % Laboratory manifestations: Anemia 70-90 % Leukocytosis 20-30 % Microscopic hematuria 30-50 % Elevated erythrocyte sedimentation rate>90 %
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Clinical and Laboratory Features of Infective Endocarditis

Rheumatoid factor 50 % Circulating immune complexes 65-100 % Decreased serum complement 5-40 %

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Common Peripheral Manifestations of Infective Endocarditis. Splinter hemorrhages (A) are normally seen under the fingernails. They are usually linear and red for the first-two to three days and brownish thereafter. Panel B shows conjunctival petechiae. Osler's nodes (Panel C) are tender, subcutaneous nodules, often in the pulp of the digits or the thenar eminence. Janeway's lesions (Panel D) are nontender, erythematous, hemorrhagic, or pustular lesions, often on the palms or soles.
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Noncardiac Manifestations
Janeways lesions. Hemorrhagic, infarcted macules and papules on the volar fingers in a patient with S. aureus endocarditis.

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Noncardiac Manifestations
Septic vasculitis associated with bacteremia. Dermal nodule with hemorrhage and necrosis on the dorsum of a finger. This type of lesion occurs with bacteremia (e.g., S. aureus) and fungemia (e.g., Candida tropicalis).

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Noncardiac Manifestations
subconjunctival hemorrhage. Submucosal hemorrhage of the lower eyelid in an elderly diabetic with enterococcal endocarditis; splinter hemorrhages in the midportion of the nail bed and Janeway lesions were also present.
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Noncardiac Manifestations
Splinter hemorrhages, embolic Subungual hemorrhages in the midportion of the nail bed (quite different in comparison to traumatic splinter hemorrhages) was noted in several fingernails in a 60-year-old female with enterococcal endocarditis, who had associated subconjunctival hemorrhage.
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Splinter haemorrhages are linear haemorrhages lying parallel to the long axis of finger or toe nails.

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Noncardiac Manifestations
Osler's nodes. Violaceous, tender nodules on the volar fingers associated with minute infective emboli or immune complex deposition.

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Noncardiac Manifestations
Septic emboli with hemorrhage and infarction due to acute Staphylococcus aureus endocarditis.

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Noncardiac Manifestations

Vasculitis
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Clubbing. Seen in patients with chronic lung disease, cyanotic heart disease, cirrhosis and infective endocarditis.

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Infective endocarditis: metastatic infections due to emboli.

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Noncardiac Manifestations
Computed tomography of the abdomen showing large embolic infarcts in the spleen and left kidney of a patient with Bartonella endocarditis.

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The Duke Criteria for the Clinical Diagnosis of Infective Endocarditis

MAJOR CRITERIA: Positive blood culture - Typical microorganism for infective endocarditis from two separate blood cultures - Viridans streptococci, Streptococcus bovis, HACEK group, or - Community-acquired Staphylococcus aureus or enterococci in the absence of a primary focus, or Persistently positive blood culture, defined as recovery of a microorganism consistent with infective endocarditis from: - Blood cultures drawn >12 h apart; or - All of three or a majority of four or more separate blood cultures, with first and last drawn at least 1 h apart

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The Duke Criteria for the Clinical Diagnosis of Infective Endocarditis

MAJOR CRITERIA: Evidence of endocardial involvement Positive echocardiogram - Oscillating intracardiac mass on valve or supporting structures or in the path of regurgitant jets or in implanted material, in the absence of an alternative anatomic explanation, or - Abscess, or - New partial dehiscence of prosthetic valve, or New valvular regurgitation (increase or change in preexisting murmur not sufficient)

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The Duke Criteria for the Clinical Diagnosis of Infective Endocarditis

MINOR CRITERIA : Predisposition: predisposing heart condition or injection drug use Fever 38.0C Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, Janeway lesions Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth's spots, rheumatoid factor
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The Duke Criteria for the Clinical Diagnosis of Infective Endocarditis

MINOR CRITERIA :
Microbiologic evidence: positive blood culture but not meeting major criterion as noted previously or serologic evidence of active infection with organism consistent with infective endocarditis Echocardiogram: consistent with infective endocarditis but not meeting major criterion
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The Duke Criteria for the Clinical Diagnosis of Infective Endocarditis

Documentation of two major criteria, of one major and three minor criteria, or of five minor criteria allows a clinical diagnosis of definite endocarditis.

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INFECTIVE ENDOCARDITIS

Vegetations (arrows) due to viridans streptococcal endocarditis involving the mitral valve.
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Characteristic sites of vegetations within the heart. In the presence of aortic insufficiency, vegetations characteristically occur on the ventricular surface of the aortic valve (A) or on the chordae tendinae or papillary muscles (B). In mitral regurgitation, the vegetations characteristically are located on the atrial surface of the mitral valve (C) or at sites of jet lesions (D) on the atrial wall.

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Classification of infective endocarditis due to recommendation of Ukranian society of cardiologists (confirmed by VI National Congress of Ukranian Cardiologists, 20000.

Activity of process: active, nonactive. Native valvular endocarditis: primary, secondary (trauma, foreign body); prosthetic valve endocarditis. Site: mitral valve, aortic valve, tricuspid valve, valve of the pulmonary artery, endocardium. Etiology: Gram-positive bacilli, Gram-negative bacilli, L-forms, rickttsia, fungi Stage of valvular disease, of cardiac insufficiency. Complications.
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Antibiotic Treatment for Infective Endocarditis Caused by Common Organisms

Streptococci Penicillin-susceptible streptococci, S. bovis Penicillin G 2-3 million units IV q4h for 4 weeks Penicillin G 2-3 million units IV q4h plus gentamicin 1 mg/kg IM or IV q8h, both for 2 weeks Ceftriaxone 2 g/d IV as single dose for 4 weeks Vancomycind 15 mg/kg IV q12h for 4 weeks
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Antibiotic Treatment for Infective Endocarditis Caused by Common Organisms

Relatively penicillin-resistant streptococci - Penicillin G 3 million units IV q4h for 4-6 weeks plus gentamicin 1 mg/kg IV q8h for 2 weeks Penicillin-resistant streptococci, pyridoxalrequiring streptococci (Abiotrophia spp.) - Penicillin G 3-4 million units IV q4h plus gentamicinc 1 mg/kg IV q8h, both for 4-6 weeks

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Antibiotic Treatment for Infective Endocarditis Caused by Common Organisms

Enterococci Penicillin G 3-4 million units IV q4h plus gentamicinc 1 mg/kg IV q8h, both for 4-6 weeks Ampicillin 2 g IV q4h plus gentamicin 1 mg/kg IV q8h, both for 4-6 weeks Vancomycin 15 mg/kg IV q12h plus gentamicin 1 mg/kg IV q8h, both for 4-6 weeks

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Antibiotic Treatment for Infective Endocarditis Caused by Common Organisms

Staphylococci Methicillin-susceptible, infecting native valves (no foreign devices) Nafcillin or oxacillin 2 g IV q4h for 4-6 weeks plus (optional) gentamicinc 1 mg/kg IM or IV q8h for 3-5 days Cefazolin 2 g IV q8h for 4-6 weeks plus (optional) gentamicin 1 mg/kg IM or IV q8h for 3-5 days Vancomycin 15 mg/kg IV q12h for 4-6 weeks
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Antibiotic Treatment for Infective Endocarditis Caused by Common Organisms

Methicillin-resistant, infecting native valves (no foreign devices) (Staphylococci) Vancomycin 15 mg/kg IV q12h for 4-6 weeks Methicillin-susceptible, infecting prosthetic valves (Staphylococci) Nafcillin or oxacillin 2 g IV q4h for 6-8 weeks plus gentamicin 1 mg/kg IM or IV q8h for 2 weeks plus rifampin 300 mg PO q8h for 6-8 weeks
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Antibiotic Treatment for Infective Endocarditis Caused by Common Organisms

Methicillin-resistant, infecting prosthetic valves (Staphylococci) Vancomycin 15 mg/kg IV q12h for 6-8 weeks plus gentamicin 1 mg/kg IM or IV q8h for 2 weeks plus rifampin 300 mg PO q8h for 6-8 weeks HACEK organisms Ceftriaxone 2 g/d IV as single dose for 4 weeks Ampicillin 2 g IV q4h plus gentamicin 1 mg/kg IM or IV q8h, both for 4 weeks
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Indications for Cardiac Surgical Intervention in Patients with Endocarditis

Surgery required for optimal outcome Moderate to severe congestive heart failure due to valve dysfunction Partially dehisced unstable prosthetic valve Persistent bacteremia despite optimal antimicrobial therapy Lack of effective microbicidal therapy (e.g., fungal or Brucella endocarditis) S. aureus prosthetic valve endocarditis with an intracardiac complication Relapse of prosthetic valve endocarditis after optimal antimicrobial therapy Persistent unexplained fever (10 days) in culture-negative prosthetic valve endocarditis
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Indications for Cardiac Surgical Intervention in Patients with Endocarditis

Surgery to be strongly considered for improved outcomea Perivalvular extension of infection Poorly responsive S. aureus endocarditis involving the aortic or mitral valve Large (>10-mm diameter) hypermobile vegetations with increased risk of embolism Persistent unexplained fever (10 days) in culturenegative native valve endocarditis Poorly responsive or relapsed endocarditis due to highly antibiotic-resistant enterococci or gram-negative bacilli 53

Prevention

Approximately 15-25% of cases of IE are a consequence of invasive procedures that produce a significant bacteremia. Because only 50% of those who developed valvular infection following a procedure were identified as being candidates for antibiotic prophylaxis, only approximately 10% of cases of IE can be prevented by the administration of preprocedure antibiotics. Maintaining good oral hygiene is probably more effective in the overall prevention of valvular infection because gingivitis is the most common source of spontaneous bacteremias. The American Heart Association periodically compiles recommendations for IE prophylaxis.