Infective Endocarditis,

 

A disease resulting from infection primarily of the valvular endocardium and occasionally the mural endocardium

Acute endocarditis: Aggressive course, usually caused by more virulent organisms, such as Staphylococcus aureus, group B streptococcus,may not have underlying valve lesion

Subacute endocarditis: Indolent course, usually caused by alpha-hemolytic streptococci, enterococci (usually in setting of underlying structural valve disease)

Endocarditis in intravenous drug abusers: Commonly involves the tricuspid valve. Staphylococcus aureus is the most common infecting organism.

Early prosthetic valve endocarditis: Occurs within 60 days of valve implantation. Staphylococci, gram-negative bacilli and Candida are common infecting organisms.

Late prosthetic valve endocarditis: Occurs 60 days or longer after valve implantation. Staphylococcus epidermidis, alpha-hemolytic streptococci and enterococci are common infecting organisms.

 

System(s) affected: Cardiovascular, Skin/Exocrine, Pulmonary, Endocrine/Metabolic, Renal/Urologic, Hemic/Lymphatic/Immunologic

Incidence/Prevalence in USA: 1.7–4.2/100,000; 0.32–1.3/1000 hospital admissions

Predominant age: All ages

Predominant sex: Male > Female (slightly)

 

SIGNS AND SYMPTOMS

Fever, may be high, low or absent. May be only symptom in prosthetic valve endocarditis.

Night sweats, chilly sensation

Malaise, myalgia, joint pain

Back pain, may be severe

Anorexia, weight loss

Stiff neck

Delirium, headache

Paralysis, hemiparesis, aphasia

Numbness, muscle weakness

Cold extremity with pain

Bloody urine, may be gross or microscopic

Bloody sputum, from septic pulmonary emboli

Petechiae

Conjunctival hemorrhage

Hemorrhagic or necrotic pustule

Pain of finger tip, or toe tip (subjective symptom of Osler node)

Chest pain, shortness of breath, cough

Pallor

Roth spot

Osler node

Janeway lesion

Heart murmur, may be absent

Neck vein distention

Gallops

Rales

Cardiac arrhythmia

Pericardial rub

Pleural friction rub

Splenomegaly

 

CAUSES

Staphylococcus aureus is a causative organism in all types of endocarditis, especially acute endocarditis and endocarditis seen in IV drug abusers

Acute endocarditis

Staphylococcus aureus

Streptococcus groups A, B, C, G

Haemophilus influenzae

Haemophilus parainfluenzae

Streptococcus pneumoniae

Staphylococcus lugdunensis

Enterococcus species

Neisseria gonorrhoeae

Subacute endocarditis

Alpha-hemolytic streptococci (viridans streptococci)

Streptococcus bovis

Enterococcus species (E. faecalis, E. faecium, E. durans)

Haemophilus aphrophilus and H. paraphrophilus

Actinobacillus actinomycetemcomitans

Cardiobacterium hominis

Eikenella corrodens

Kingella kingae

Staphylococcus aureus

Endocarditis in intravenous drug-abusers

Staphylococcus aureus

Pseudomonas aeruginosa

Burkholderia cepacia

Other gram-negative bacilli

Enterococcus species

Candida species

Early prosthetic valve endocarditis

Staphylococcus aureus

Staphylococcus epidermidis

Gram-negative bacilli

Candida species

Aspergillus species

Late prosthetic valve endocarditis

Alpha-hemolytic streptococci (viridans streptococci)

Enterococcus species

Staphylococcus epidermidis

Candida species

Aspergillus species

Culture-negative endocarditis

5–10%

Patients on antibiotics

Bartonella quintana (homeless people)

Bartonella henselae (cat owners)

Brucella

Fungi

Coxiella burnetii (Q fever)

Chlamydia trachomatis

Chlamydia psittaci

 

RISK FACTORS

Conditions predisposed to development of endocarditis

Prosthetic cardiac valves, including bioprosthetic and homograft valves

Previous bacterial endocarditis, even in the absence of heart disease

Most congenital cardiac malformations

Rheumatic and other acquired valvular dysfunction, even after valvular surgery

Hypertrophic cardiomyopathy

Mitral valve prolapse with valvular regurgitation

Indwelling intravascular devices

Dental or surgical procedures that may cause transient bacteremia leading to endocarditis in susceptible hosts

Dental procedures known to produce gingival irritation, including professional cleaning

Tonsillectomy and/or adenoidectomy

Surgical operations that involve intestinal or respiratory mucosa

Bronchoscopy with a rigid bronchoscope

Sclerotherapy for esophageal varices

Esophageal dilatation

Gallbladder surgery

Cystoscopy

Urethral dilatation

Urethral catheterization if urinary tract infection is present

Urinary tract surgery if urinary tract infection is present

Prostatic surgery

Incision and drainage of infected tissue

Vaginal hysterectomy

Vaginal delivery in the presence of infection

 

LABORATORY

Positive blood cultures taken at different times

2-dimensional echocardiography, not always positive for vegetations (transesophageal echocardiography has high sensitivity)

Leukocytosis in acute endocarditis

Anemia in subacute endocarditis

Elevated erythrocyte sedimentation rate

Decreased C3, C4, CH50 in subacute endocarditis

Hematuria, microscopic or macroscopic

Rheumatoid factor in subacute endocarditis

Serologies for Chlamydia, Q fever (Coxiella) and Bartonella may be useful in “culture-negative” endocarditis

 

Drugs that may alter lab results: Antibiotics may make blood cultures falsely negative

 

Disorders that may alter lab results:

Endocarditis caused by fungi, Chlamydia trachomatis, Chlamydia psittaci, Coxiella burnetii, Bartonella species may be associated with negative blood cultures

Prolonged incubation of blood cultures is needed in endocarditis caused by fastidious organisms, e.g., HACEK organisms (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella species), Brucella species

 

PATHOLOGICAL FINDINGS

Vegetations on the affected endocardium are composed of platelets, fibrin and colonies of micro-organisms. Destruction of valvular endocardium, perforation of valve leaflets, rupture of chordae tendineae, abscesses of myocardium, rupture of sinus of Valsalva, pericarditis may occur.

Emboli and/or infarction may be found in different body organs. Abscesses and micro-abscesses may be found in different organs. Kidneys may show embolic and/or immune-complex glomerulonephritis.

 

IMAGING

Pulmonary ventilation perfusion scan may be useful in right-sided endocarditis

Computerized axial tomographic scan may be useful in locating abscesses

 

DIAGNOSTIC PROCEDURES

Transesophageal echocardiography is useful, especially in prosthetic or bioprosthetic valve endocarditis and S. aureus endocarditis associated with intravascular catheter

Cardiac catheterization may be indicated to ascertain the degree of valvular damage

Aortic root injection may be useful when aortic root abscess or rupture of sinus of Valsalva is suspected

Duke criteria for diagnosis of infective endocarditis

2 major criteria, or

1 major and 3 minor criteria, or

5 minor criteria

Major criteria

Positive blood culture

- Typical microorganism for infective endocarditis from 2 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 more than 12 hours apart, or all of 3 or a majority of 4 or more separate blood cultures, with first and last drawn at least 1 hour apart

Evidence of endocardial involvement

Positive echocardiogram: (a) oscillating intracardiac mass, on valve or supporting structures, or in  the path of regurgitant jets, or on implanted material, in the absence of an alternative anatomic explanation, or (b) abscess, or (c) new partial dehiscence of prosthetic valve

New valvular regurgitation (increase or change in pre-existing murmur not sufficient)

Minor criteria

Predisposition: predisposing heart condition or intravenous drug use

Fever ≥ 38.0°C (100.4°F)

Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhage, Janeway lesions

Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth spots, rheumatoid factor

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 as previous noted

† Including nutritional variant strains

†† HACEK = Haemophilus spp, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella spp, Kingella kingae

††† Excluding single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis

 

TREATMENT

APPROPRIATE HEALTH CARE

Initial hospitalized care

Intensive care may be needed in critically ill patients

Outpatient home intravenous antibiotic therapy may be utilized in selected patients who are stable and reliable

 

GENERAL MEASURES

Treatment for congestive heart failure if it occurs

Oxygen treatment may be indicated

Hemodialysis may be used in patients who develop renal failure

 

SURGICAL MEASURES

Cardiac surgery to replace infected valve may be performed before antibiotic treatment course is completed when (any one):

There is evidence of congestive heart failure due to valve incompetence,

Multiple major systemic emboli have occurred,

The infection is caused by resistant organisms, e.g., fungus, Pseudomonas aeruginosa,

There is dehiscence of infected prosthetic valve,

There is relapse of prosthetic valve endocarditis,

There is persistent bacteremia despite antibiotic treatment

 

ACTIVITY

Bedrest is indicated initially

Ambulation when clinically improved

 

DIET No special diet

 

PATIENT EDUCATION

Instruct patient regarding importance of dental hygiene

Emphasize to patient that it is important to take antibiotic prophylaxis when undergoing certain dental/surgical procedures

Give the patient an AHA wallet card listing antibiotic regimens for prophylaxis. Obtain the AHA wallet card, 78–1005 (CP), from local chapters of American Heart Association.

 

MEDICATIONS DRUG(S) OF CHOICE

Endocarditis due to penicillin-susceptible viridans streptococci and Streptococcus bovis: Aqueous crystalline penicillin G 10–20 million U/24 h IV in 4–6 equally divided doses, plus gentamicin [see Other Notes] for 2 weeks (6 weeks for prosthetic valve endocarditis). In patients with native valve endocarditis: Those older than 65 years of age, those with impairment of the eighth nerve or of renal function, or those with central nervous system involvement, use aqueous crystalline penicillin G only, in the same dosage alone for 4 weeks.

Endocarditis due to enterococci: Aqueous crystalline penicillin G 20–40 million U/24 h in 6 equally divided doses, plus gentamicin (see Other Notes) for 4–6 weeks (6 weeks for prosthetic valve endocarditis). Test the enterococcal strain in vitro for high-level resistance to gentamicin and streptomycin (minimal inhibitory concentration [MIC] > 2000 µg/mL). Use streptomycin, 1 gm IM every 24 hours, instead of gentamicin if there is high-level resistance to gentamicin and not to streptomycin.

Endocarditis of native valve due to staphylococcus: Oxacillin or nafcillin 2 g IV every 4 h for 6 weeks. For the first 3–5 days, gentamicin (see Other Notes) may be added.

Prosthetic valve endocarditis due to staphylococci: Vancomycin 15 mg/kg (usual dose 1 g) IV infused over 1 h every 12 h, plus rifampin 300 mg po every 8 h, both for 6 weeks, plus gentamicin (see Other Notes) for the first 2 weeks

Endocarditis due to HACEK organisms (Haemophilus species, Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae) - ceftriaxone 2 gm IM or IV every 24 h for 4 weeks

 

Contraindications: For patients who are allergic to penicillin, use alternative drugs

 

Precautions:

In patients with renal impairment, dosage adjustment should be made for penicillin G, gentamicin, cefazolin, vancomycin

Rapid infusion of vancomycin (less than one hour) may cause “red-neck syndrome”, an intense redness or rash over the upper half of the body. This is due to histamine release and not an allergic reaction. It will disappear when the rate of infusion is reduced.

 

Significant possible interactions:

The combination of vancomycin and gentamicin may cause increased incidence of renal toxicity

Rifampin may increase the requirement for coumarin oral anticoagulant and oral hypoglycemic agents

 

ALTERNATIVE DRUGS

For patients who are allergic to penicillin

Endocarditis due to penicillin-susceptible viridans streptococci and Streptococcus bovis: ceftriaxone 2 g IM or IV once daily for 4 weeks or ceftriaxone 2 g IV plus gentamicin 3 mg/kg once daily for 2 weeks (not to be used in patients with immediate type hypersensitivity to penicillin), or vancomycin 15 mg/kg (usual dose 1 g) IV infused over 1 h every 12 h for 4 weeks (6 weeks for prosthetic valve endocarditis)

Endocarditis due to enterococci: Desensitization to penicillin should be considered. Vancomycin 15 mg/kg (usual dose 1 g) IV infused over 1 h every 12 h, plus gentamicin (see Other Notes) for 4–6 weeks (6 weeks for prosthetic valve endocarditis).

Endocarditis of native valve due to staphylococcus: Cefazolin 2 gm IV every 8 h (not to be used in patients with immediate-type hypersensitivity to penicillin), or vancomycin 15 mg/kg (usual dose 1 g) IV infused over 1 h every 12 h, for 6 weeks

 

FOLLOWUP

PATIENT MONITORING

Gentamicin blood levels should be performed if used for more than 5 days, and in patients with renal dysfunction. Peak gentamicin level should be around 3 µg/mL and trough less than 1 µg/mL.

Vancomycin blood levels should be performed in patients with renal dysfunction. Desired peak level is 30–45 mcg/mL and trough less than 10 mcg/mL.

Twice weekly BUN and serum creatinine should be performed while the patient is receiving gentamicin

Consider audiometry baseline and follow-up during long-term aminoglycoside therapy

 

PREVENTION/AVOIDANCE

Dental caries should be treated while the patient is being treated for endocarditis

Patients should maintain good oral hygiene

Antibiotic prophylaxis should be given to the patient who is undergoing dental or surgical procedures that may cause transient bacteremia

Standard antibiotic regimen for dental/oral/upper respiratory tract procedures: (may be used in patients with prosthetic valves)

Amoxicillin 2 g orally 1 h before procedure

For patients who are allergic to penicillin: clindamycin 600 mg orally 1 h before a procedure

Alternate antibiotic regimens for dental/oral/upper respiratory tract procedures

For patients unable to take oral medications: Ampicillin 2.0 g IV (or IM) 30 minutes before procedure

For patients who are allergic to penicillin: Clindamycin 600 mg IV 30 minutes before a procedure

Standard antibiotic regimen for genitourinary/gastrointestinal procedures

Ampicillin 2.0 g IV (or IM) plus gentamicin 1.5 mg/kg IV (or IM) (not to exceed 120 mg) 30 minutes before procedure

For patients who are allergic to penicillin: vancomycin 1.0 g IV infused over one hour plus gentamicin 1.5 mg/kg IV (or IM) (not to exceed 120 mg); complete infusion 30 minutes before procedure

Alternate oral regimen for moderate-risk patients undergoing genitourinary/gastrointestinal procedures

Amoxicillin 2.0 g orally one hour before procedure or ampicillin 2 g IV (or IM) 30 minutes before procedure

For patients who are allergic to penicillin: vancomycin 1.0 g IV infused over 1 hour; complete infusion 30 minutes before procedure

 

POSSIBLE COMPLICATIONS

Congestive heart failure

Ruptured valve cusp

Sinus of Valsalva aneurysm

Aortic root abscesses

Myocardial abscesses

Myocardial infarction

Pericarditis

Cardiac arrhythmia

Meningitis

Cerebral emboli

Brain abscesses

Ruptured mycotic aneurysm

Septic pulmonary infarcts

Splenic infarcts

Arterial emboli and infarcts

Arthritis

Myositis

Glomerulonephritis

Acute renal failure

Mesenteric infarct

 

EXPECTED COURSE/PROGNOSIS

In staphylococcal endocarditis, fever and positive blood cultures may persist up to 10 days after appropriate treatment started

In streptococcal endocarditis, there should be clinical response within 48 hours of antibiotic treatment and blood cultures should be negative soon after antibiotic treatment is started

Prognosis depends largely on the possible complications

 

MISCELLANEOUS

ASSOCIATED CONDITIONS

Most patients who have tricuspid valve endocarditis are intravenous drug abusers or have indwelling IV lines

 

Geriatric: Prognosis is worse in elderly people

 

PREGNANCY

Gentamicin should be used with caution; avoid use if possible

 

SYNONYMS

Bacterial endocarditis

Infectious endocarditis

Subacute bacterial endocarditis

Subacute infective endocarditis

Acute bacterial endocarditis

Acute infective endocarditis

 

OTHER NOTES

 Gentamicin dosing: 3 mg/kg/day in divided doses every 8–12 hours, depending on renal function and results of peak/trough measures.