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Infective Endocarditis

Uaepong Limpapanasit July 5, 2010


- Mandell 7th ed - Infective Endocarditis & Prevention of Infective Endocarditis, Guidelines From the American Heart Association - Harrison 17th ed

Definition
Infection of the endocardial surface Presence of microorganism in the lesion Sites :
Valve Septal defect Mural endocardium Arteriovenous shunt PDA Coarctation of aorta

Endarteritis

Classification
Acute vs Subacute
Acute : S.aureus, S.pyogenes, S.pneumoniae, N.gonorrhea Subacute : S.viridans, enterococci, CoNS, HACEK

Etiologic agents

Epidermiology
10,000-20,000 new cases in USA (AHA) Mean age : 57.9 Male : Female 1.7 : 1 Site :
Mitral valve alone : 28-45% of case Aortic valve alone : 5-36% Mitral and aortic valve : 0-6% Pulmonary valve : < 1%

Underlying
Rheumatic heart disease : 37 - 76 % Congenital heart disease : 6 - 24% Degenerative cardiac lesions : 30 - 40% Many other conditionsmay predispose to IE
bicuspid aortic valve arterioarterial fistulas hemodialysis shunts or fistulas intracardiac prosthesis or pacemaker wires

Etiologic agent
Agent Streptococci Viridans streptococci Enterococci Other streptococci Staphylococci Coagulase-positive Coagulase-negative Gram-negative aerobic bacilli Fungi Miscellaneous bacteria Mixed infections Culture-negative Cases (%) 60-80 30-40 5-18 15-25 20-35 10-27 1-3 1.5-13 2-4 <5 1-2 <5-24

Community acquired :
Oral cavity, skin, URS : Viridans streptococci, Staphylococci, HACEK (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella) GI : Streptococcus bovis GU : Enterococci

Hospital acquired :
Catheter, wound, H/D : S.aureus Prosthetic valve endocarditis : Coagulase-negative staphylococci, S.aureus, gram neg bacilli, fungi Pacemaker/defribillator assoc. endocarditis : S.aureus, Coagulase-negative staphylococci IVDU : S.aureus, P.aeruginosa, Candida spp., Polymicrobial

Pathogenesis
Valve surface injury Formation of sterile vegetationthe lesions of nonbacterial thrombotic endocarditis (NBTE) During transient bacteremia, bacteria then must reach this site and adhere to and invade the involved tissue Bacterial multiplication and vegetative growth.

NBTE
Endothelial injury
At the site of impact of high-velocity blood jets e.g. small VSD, valvular stenosis On the low-pressure site of cardiac structural lesion MR, AS, AR, VSD, complex congenital HD

Hypercoagulable state (marantic endocarditis)


Malignancy, SLE, APS

Incidence of bacteremia after various procedure


Procedure Dental
Dental extraction Periodontal surgery Chewing candy or paraffin Tooth brushing Oral irrigation device

% Positive Blood Cultures 18-85 32-88 17-51 0-26 27-50 15 28-38 16

Gastrointestinal
-Upper gastrointestinal endoscopy Sigmoidoscopy/ colonoscopy Barium enema Percutaneous needle biopsy of liver 8-12 0-9.5 11 3-13

Urologic
Urethral dilation Urethral catheterization Cystoscopy Transurethral prostatic resection 18-33 8 0-17 12-46

Upper Airway
Bronchoscopy (rigid scope) Tonsillectomy Nasotracheal suctioning/ intubation

Obstetric/gynecologic
Normal vaginal delivery 0-11 0 0 Punch biopsy of the cervix Removal/insertion of IUD

Everett ED, Hirschmann JV. Transient bacteremia and endocarditis prophylaxis: A review. Medicine (Baltimore). 1977;56:61.

Clinical manifestation
Incubation period
Acute IE : less than 2 wk Subacute IE : approximate 5 wk

Result from
Cytokine production constitutional symtom Embolization infection or infarction Hematogenous infection bacteremia Immune complex tissue injury

Fever : common
usually remittent, and the patient's temperature rarely exceeds 40C, except in acute IE.

Nonspecific symptoms
such as anorexia, weight loss, malaise, fatigue, chills, weakness, nausea, vomiting, and night sweats are common, especially in subacute cases.

Cardiac manifestations
Audible heart murmurs occur in greater than 85% of cases Changing murmur or new regurgitant murmur CHF Perivalvular abscess or fistula Pericarditis Heart block Myocardial infarction

Peripheral manifestations
Clubbing fingers Splinter hemorrhages Petechiae Osler nodes Janeway lesions Roth spots

Major embolic episodes


Splenic artery emboli with infarction Renal infarctions Pulmonary emboli Coronary artery emboli Major vessel emboli

Neurologic manifestations
Embolic stroke as the most common manifestation Mycotic aneurysms of the cerebral circulation subarachnoid hemorrhage. Other features include seizures, severe headache, visual changes (particularly homonymous hemianopsias), choreoathetoid movements, mononeuropathy, and cranial nerve palsies. Toxic encephalopathy

Symptoms Fever Chills Weakness Dyspnea Sweats Anorexia Weight loss Malaise Cough Skin lesions Stroke Nausea/vomiting Headache Myalgia/arthralgia Edema Chest pain Abdominal pain and delirium/coma Delirium/coma Hemoptysis

Patients Affected (%) 80 40 40 40 25 25 25 25 25 20 20 20 20 15 15 15 15 10-15 10

Signs Fever Heart murmur Changing murmur New murmur Embolic phenomenon Skin manifestations Osler nodes Splinter hemorrhages Petechiae Janeway lesion Splenomegaly Septic complications (e.g., pneumonia, meningitis) Mycotic aneurysms Clubbing Retinal lesion Signs of renal failure

Patients (%) 90 85 5-10 3-5 >50 18-50 10-23 15 20-40 <10 20-57 20 20 12-52 2-10 10-25

Data from Lerner PI, Weinstein L. Infective endocarditis in the antibiotic era. N Engl J Med. 1966;274:199; Pelletier LL, Petersdorf RG. Infective endocarditis: A review of 125 cases from the University of Washington Hospitals, 1963-1972. Medicine (Baltimore). 1977;56:287; Venezio FR, Westenfelder GO, Cook FV, et al. Infective endocarditis in a community hospital. Arch Intern Med. 1982;142:789; and Weinstein L, Rubin RH. Infective endocarditis1973. Prog Cardiovasc Dis. 1973;16:239.

Diagnosis : The Modified Duke Criteria


Definite Infective Endocarditis Pathologic criteria Microorganisms: shown by culture or histology in a vegetation, or in a vegetation that has embolized, or in an intracardiac abscess, or Pathologic lesions: vegetation or intracardiac abscess present, confirmed by histology showing active endocarditis Clinical criteria (using specific definitions for these terms*) Presence of 2 major criteria, or Presence of 1 major and 3 minor criteria, or Presence of 5 minor criteria Possible Infective Endocarditis Findings consistent with infective endocarditis that fall short of Definite, but not Rejected Rejected Firm alternative diagnosis explaining evidence of infective endocarditis, or Resolution of endocarditis syndrome with antibiotic therapy for 4 days, or No pathologic evidence of infective endocarditis at surgery or autopsy, after antibiotic therapy for 4 days

Major criteria: A. Positive blood culture for Infective Endocarditis 1- Typical microorganism consistent with IE from 2 separate blood cultures, as noted below: viridans streptococci, Streptococcus bovis, or HACEK* group, or community-acquired Staphylococcus aureus or enterococci, in the absence of a primary focus or 2- Microorganisms consistent with IE from persistently positive blood cultures defined as: 2 positive cultures of blood samples drawn >12 hours apart, or all of 3 or a majority of 4 separate cultures of blood (with first and last sample drawn 1 hour apart) B. Evidence of endocardial involvement 1- Positive echocardiogram for IE defined as : oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation, or abscess, or new partial dehiscence of prosthetic valve or 2- New valvular regurgitation (worsening or changing of preexisting murmur not sufficient) Minor criteria: - Predisposition: predisposing heart condition or intravenous drug use - Fever: temperature > 38.0 C (100.4 F) - Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions - Immunologic phenomena: glomerulonephritis, Osler's nodes, Roth spots, and rheumatoid factor - Microbiological evidence: positive blood culture but does not meet a major criterion as noted above or serological evidence of active infection with organism consistent with IE - Echocardiographic findings: consistent with IE but do not meet a major criterion as noted above

Lab
CBC : ACD, leucocytosis UA : proteinuria, microscopic hematuria Elevated ESR/CRP Decreased srum complement Blood culture : At least three blood culture sets should be obtained in the first 24 hours. More specimens may be necessary if the patient has received ATB during the preceding 2 weeks. Ecchocardiography

Echocardiography
Echocardiography should be performed in all cases of suspected IE (Class I, Level of Evidence: A) TEE to be more sensitive than TTE If the clinical suspicion is relatively low or imaging is likely to be of good quality, then it is reasonable to perform TTE If any circumstances preclude securing optimal echocardiographic windows, including chronic obstructive lung disease, previous thoracic surgery, morbid obesity, or other conditions, then TEE should be performed instead of TTE

Treatment
Antimicrobial therapy
Parenteral, prolonged, bactericidal

Surgical therapy

Antimicrobial therapy
Viridans Group Streptococci and S bovis S pneumoniae, S pyogenes, and Groups B, C, and G Streptococci S aureus Coagulase-Negative Staphylococci Enterococci HACEK Microorganisms Non-HACEK Gram-Negative Bacilli Culture-Negative Endocarditis Fungi

Penicillin-susceptible streptococci and S. bovis


Penicillin G 12-18 million unit divided q 4-6h iv 4 wk or Ceftriaxone 2gm iv od 4 wk or Vancomycin 15 mg/kg iv q12h 4 wk

Relatively Penicillin-resistant streptococci


Penicillin G 24 mU divided q 4-6h iv or Ceftriaxone 4 wk plus Gentamicin 3 mg/kg iv od 2 wk or Vancomycin 15 mg/kg iv q12h 4 wk

Prosthetic Valves or Other Prosthetic Material Caused by Viridans Group Streptococci and Streptococcus bovis
Penicillin-susceptible
Penicillin G 24 mU divided q 4-6h iv or Ceftriaxone 6 wk plus Gentamicin 3 mg/kg iv od 2 wk or Vancomycin 15 mg/kg iv q12h 6 wk

Penicllin-resistant
Penicillin G 24 mU divided q 4-6h iv or Ceftriaxone 6 wk plus Gentamicin 3 mg/kg iv od 6 wk or Vancomycin 15 mg/kg iv q12h 6 wk

Staphylococci in the Absence of Prosthetic materials


Oxacillin-susceptible
Nafcillin or oxacillin 12 g/24 h IV in 46 divided doses or Cefazolin 6 g/24 h IV in 3 divided doses 6 wk plus Gentamicin 3 mg/ kg IV/IM in 2 or 3 divided doses 35 d

Oxacillin-resistant
Vancomycin 15 mg/kg iv q12h 6 wk

Prosthetic Valve Endocarditis Caused by Staphlococci


Oxacillin-susceptible
Nafcillin or oxacillin 12 g/24 h IV in 46 divided doses 6 wk plus Rifampin 900 mg per 24 h IV/PO in 3 divided doses 6 wk plus Gentamicin 3 mg/kg IV/IM in 2 or 3 divided doses 2 wk

Oxacillin-resistant
Vancomycin 15 mg/kg iv q12h 6 wk plus Rifampin 900 mg per 24 h IV/PO in 3 divided doses 6 wk plus Gentamicin 3 mg/kg IV/IM in 2 or 3 divided doses 2 wk

Native Valve or Prosthetic Valve Enterococcal Endocarditis Caused by Strains Susceptible to Penicillin, Gentamicin, and Vancomycin
Ampicillin 12 g/24 h IV in 6 divided doses or Penicillin G 1830 mU/ IV in 6 equally divided doses 46 wk plus Gentamicin 3 mg/kg IV/IM in 2 or 3 divided doses 4-6 wk Vancomycin 15 mg/kg iv q12h 6 wk plus Gentamicin 3 mg/kg IV/IM in 2 or 3 divided doses 6 wk

Native or Prosthetic Valve Enterococcal Endocarditis Caused by Strains Resistant to Penicillin and Susceptible to Aminoglycoside and Vancomycin Vancomycin 15 mg/kg iv q12h 6 wk plus Gentamicin 3 mg/kg IV/IM in 2 or 3 divided doses 6 wk

Native and Prosthetic Valve Endocarditis Caused by HACEK* Microorganisms Ceftriaxone sodium 2 g IV od 4 wk Ampicillin- sulbactam 12 g IV in 4 divided doses 4 wk Ciprofloxacin1000 mg/24 h PO or 800 mg/ 24 h IV in 2 divided doses 4 wk

Culture-Negative Endocarditis
Native valve
Ampicillin-sulbactam 12 g/24 h IV in 4 divided doses 4-6 wk plus Gentamicin 3 mg/kg IV in 3 divided doses 4-6 wk or Vancomycin 30 mg/kg per 24 h IV in 2 divided doses 46 wk plus Gentamicin sulfate 3 mg/kg IV in 3 divided doses 46wk plus Ciprofloxacin 1000 mg/24 h PO or 800 mg/24 h IV in 2 divided doses 46 wk

Prosthetic valve
Vancomycin 30 mg/kg per 24 h IV in 2 divided doses 6 wk plus Gentamicin 3 mg/kg per 24 h IV in 3 divided doses 2 wk plus Cefepime 6 g/24 h IV in 3 divided doses 6 wk plus Rifampin 900 mg/24 h PO/IV in 3 divided doses 6 wk

Suspected Bartonella, culture negative


Ceftriaxone sodium 2 g/24 h IV/IM in 1 dose 6 wk plus Gentamicin 3 mg/kg per 24 h IV/ IM in 3 equally divided doses 2 wk with/ without Doxycycline 200 mg/kg per 24 h IV/ PO in 2 equally divided doses 6 wk

Fungi
Candida and Aspergillus species account for the large majority of fungal endocardial infection Treatment is a combination of a parenteral antifungal agent, usually an amphotericin B 6 wk and valve replacement.

Surgical therapy
Indication
Mod to severe CHF Partially dehisced unstable prosthetic valve Persistent bacteremia despite optimal ATB Lack of effective microbicidal therapy S.aureus prosthetic valve endocarditis with intracardiac complication Relapse after optimal ATB Vegetation size > 10 mm

Prevention
Antibiotic prophylaxis is reasonable for all dental procedures that involve manipulation of gingival tissues or periapical region of teeth or perforation of oral mucosa (including procedures on respiratory tract). Antibiotic prophylaxis solely to prevent IE is not recommended for GU or GI tract procedures.