Included in this chapter are infective endocarditis (IE), myocarditis, pericarditis, Lyme carditis, and postperfusion syndrome. Other conditions in which the cause is not well established but the host’s immune response to an infective agent is thought to play a role are also included, such as Kawasaki’s disease and postpericardiotomy syndrome. Cardiac manifestations of human immunodeficiency virus (HIV) are also included.
Infective Endocarditis
Prevalence
Infective endocarditis accounts for 0.5 to 1 of every 1000 hospital admissions, excluding postoperative endocarditis.
Pathogenesis
- 1.
Two factors are important in the pathogenesis of IE: (1) a damaged area of endothelium and (2) bacteremia, even transient. The presence of structural abnormalities of the heart or great arteries, with a significant pressure gradient or turbulence, produces endothelial damage. Such endothelial damage induces thrombus formation with deposition of sterile clumps of platelet and fibrin (nonbacterial thrombus). Prosthetic valves or prosthetic materials used in surgery also promote deposition of sterile thrombus. Nonbacterial thrombus provides a nidus for bacteria to adhere and eventually form infected vegetation. Platelets and fibrin are deposited over the organisms, leading to the enlargement of the vegetation.
- 2.
Almost all patients who develop IE have a history of congenital or acquired heart disease. Drug addicts may develop endocarditis in the absence of known cardiac anomalies.
- 3.
All congenital heart defects (CHDs), with the exception of secundum-type atrial septal defect (ASD), predispose to endocarditis. More frequently encountered defects are tetralogy of Fallot (TOF), ventricular septal defect (VSD), aortic valve disease, transposition of the great arteries (TGA), and systemic-to-PA shunt. Those with a prosthetic heart valve or prosthetic material in the heart are at particularly high risk of developing endocarditis. Patients with mitral valve prolapse (MVP) with mitral regurgitation (MR) and those with rheumatic MR also are vulnerable to IE.
- 4.
Bacteremia resulting from dental procedures can cause IE. Bacteremia also occurs with activities such as chewing or brushing the teeth. Chewing with diseased teeth or gums may be the most frequent cause of bacteremia. Therefore, good dental hygiene is very important in the prevention of IE.
Pathology
Vegetation of IE is usually found on the low-pressure side of the defect, either around the defect or on the opposite surface of the defect where endothelial damage is established by the jet effect of the defect. For example, vegetations are found in the PA in patent ductus arteriosus (PDA) or systemic-to-PA shunts, on the atrial surface of the mitral valve in MR, on the ventricular surface of the aortic valve and mitral chordae in aortic regurgitation (AR), and on the superior surface of the aortic valve or at the site of a jet lesion in the aorta in patients with aortic stenosis (AS).
Microbiology
- 1.
In the past, Streptococcus viridans, enterococci, and Staphylococcus aureus were responsible for more than 90% of the cases. In recent years, this frequency has decreased to 50% to 60%, with a concomitant increase in cases caused by fungi and HACEK organisms (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella spp.). HACEK organisms are particularly common in neonates and immunocompromised children, accounting for 17% to 30% of cases.
- 2.
α-Hemolytic streptococci (S. viridans) are the most common cause of endocarditis in patients who have had dental procedures or in those with carious teeth or periodontal disease.
- 3.
Enterococci are the organisms most often found after genitourinary or gastrointestinal (GI) surgery or instrumentation.
- 4.
The organisms most commonly found in postoperative endocarditis are staphylococci.
- 5.
Intravenous (IV) drug abusers are at risk for IE caused by infection with S. aureus.
- 6.
Fungal endocarditis (which has a poor prognosis) may occur in sick neonates, in patients who are on long-term antibiotic or steroid therapy, or after open heart surgery. Fungal endocarditis is often associated with very large friable vegetations; emboli from these vegetations frequently produce serious complications.
- 7.
IE associated with indwelling vascular catheters, prosthetic material, and prosthetic valves is frequently caused by S. aureus or coagulase-negative staphylococci.
- 8.
Among newborn infants, S. aureus , coagulase-negative staphylococci, and Candida spp. are the most common causes of IE.
- 9.
A diagnosis of culture-negative endocarditis is made when a patient has clinical or echocardiographic evidence of endocarditis but persistently negative blood culture results. The most common cause of culture-negative endocarditis is current or recent antibiotic therapy or infection caused by a fastidious organism that grows poorly in vitro. Fungal endocarditis is a rare cause of culture-negative endocarditis. At times, the diagnosis can be made only by removal of vegetation (during surgery). In the United States, about 5% to 7% have culture-negative endocarditis.
Clinical Manifestations
History
- 1.
Most patients have a history of an underlying heart defect. However, some patients with bicuspid aortic valve may not have been diagnosed with the defect before the onset of the endocarditis.
- 2.
A history of a recent dental procedure or tonsillectomy is occasionally present, but a history of toothache (from dental or gingival disease) is more frequent than a history of a procedure.
- 3.
Endocarditis is rare in infancy; at this age, it usually follows open heart surgery.
- 4.
The onset is usually insidious with prolonged low-grade fever and somatic complaints, including fatigue, weakness, loss of appetite, pallor, arthralgia, myalgias, weight loss, and diaphoresis.
Physical Examination
- 1.
Heart murmur is universal (100%). The appearance of a new heart murmur and an increase in the intensity of an existing murmur are important. However, many innocent heart murmurs are also of new onset.
- 2.
Fever is common (80%–90%). Fever fluctuates between 101° and 103°F (38.3 ° and 39.4 ° C).
- 3.
Splenomegaly is common (70%).
- 4.
Skin manifestations (50%) (either secondary to microembolization or as an immunologic phenomenon) may be present in the following forms:
- a.
Petechiae on the skin, mucous membranes, or conjunctivae are the most frequent skin lesions.
- b.
Osler’s nodes (tender, pea-sized red nodes at the ends of the fingers or toes) are rare in children.
- c.
Janeway’s lesions (small, painless, hemorrhagic areas on the palms or soles) are rare.
- d.
Splinter hemorrhages (linear hemorrhagic streaks beneath the nails) also are rare.
- a.
- 5.
Embolic or immunologic phenomena in other organs are present in 50% of cases:
- a.
Pulmonary emboli may occur in patients with VSD, PDA, or a systemic-to-PA shunt.
- b.
Seizures and hemiparesis are the result of embolization to the central nervous system (CNS) (20%) and are more common with left-sided defects such as aortic and mitral valve disease or with cyanotic heart disease.
- c.
Hematuria and renal failure may occur.
- d.
Roth’s spots (oval, retinal hemorrhages with pale centers located near the optic disc) occur in fewer than 5% of patients.
- a.
- 6.
Carious teeth or periodontal or gingival disease is frequently present.
- 7.
Clubbing of fingers in the absence of cyanosis develops rarely in more chronic cases.
- 8.
Signs of heart failure may be present as a complication of the infection.
- 9.
The clinical manifestations in a neonate with IE are nonspecific (respiratory distress, tachycardia) and may be indistinguishable from septicemia or congestive heart failure (CHF) from other causes. Embolic phenomena (such as osteomyelitis, meningitis, pneumonia) are common. They may have neurologic signs and symptoms (seizures, hemiparesis, apnea).
Laboratory Studies
- 1.
Positive blood cultures are found in more than 90% of patients in the absence of previous antimicrobial therapy. Antimicrobial pretreatment reduces the yield of positive blood culture to 50% to 60%.
- 2.
A complete blood cell count shows anemia, with hemoglobin levels lower than 12 g/100 mL (present in 80% of patients), and leukocytosis with a shift to the left. Patients with polycythemia preceding the onset of IE may have normal hemoglobin.
- 3.
The sedimentation rate is increased unless there is polycythemia.
- 4.
Microscopic hematuria is found in 30% of patients.
Echocardiography
Two-dimensional echocardiography is the main modality for detecting endocardial infection ( Fig. 19-1 ). It detects the site of infection, extent of valvular damage, and cardiac function. Baseline evaluation of ventricular function and cardiac chamber dimension is important for comparison later in the course of the infection. Color Doppler is a sensitive modality for the detection of valvular regurgitation.
- 1.
Certain echocardiographic findings are included as major criteria in the modified Duke criteria. They include:
- a.
Oscillating intracardiac mass on valves or supporting structures, in the path of regurgitation jets, or on implanted material
- b.
Abscesses
- c.
New partial dehiscence of prosthetic valve
- d.
New valvular regurgitation
- a.
- 2.
Although standard transthoracic echocardiography (TTE) is sufficient in most clinical circumstances, transesophageal echocardiography (TEE) may be an important adjunct to TTE in the obese or very muscular adolescents, in postcardiac surgery patients, or in the presence of compromised respiratory function or pulmonary hyperinflation. TEE may be superior to TTE in identifying vegetations on prosthetic valves, detecting complications of LV outflow tract endocarditis (either valvular or subvalvular), and detecting aortic root abscess and involvement of sinus of Valsalva.
- 3.
The absence of vegetations on echocardiography does not in itself rule out IE. Both TTE and TEE may produce false-negative results if vegetations are small or have already embolized, and they may miss initial perivalvular abscess. Repeat examinations are indicated if suspicion exists without diagnosis of IE or worrisome clinical course during early treatment of IE.
- 4.
Conversely, a false-positive diagnosis is possible. An echogenic mass may represent a sterile thrombus, sterile prosthetic material, normal anatomic variation, an abnormal uninfected valve (previous scarring, severe myxomatous changes), or improper gain of the echocardiography machine. Echocardiographic evidence of vegetation may persist for months or years after bacteriologic cure.
- 5.
Certain echocardiographic features suggest a high-risk case or a need for surgery:
- a.
Large vegetations (greatest risk when the vegetation is >10 mm)
- b.
Severe valvular regurgitation
- c.
Abscess cavities
- d.
Pseudoaneurysm
- e.
Valvular perforation or dehiscence
- f.
Decompensated heart failure
- a.
Diagnosis
Recently, the American Heart Association ( Baddour et al, 2005 ) has recommended the modified Duke Criteria in the diagnosis and management of IE. The usefulness of the criteria has been validated in clinical studies.
There are three categories of diagnostic possibilities using the modified Duke criteria: definite, possible, and rejected ( Box 19-1 ).
- 1.
A diagnosis of “definite” IE is made by pathological evidence and fulfillment of certain clinical criteria.
- a.
Pathological evidence of IE includes (1) demonstration of microorganism by culture, (2) histology in a vegetation or from an embolic sites or an intracardiac abscess, or histologic evidence of active endocarditis demonstrated in vegetation or intracardiac abscess.
- b.
Fulfillment of clinical criteria is met by the presence of two major criteria, one major and three minor criteria, or five minor criteria as described in Box 19-2 . Major clinical criteria are (1) positive blood cultures for acceptable microorganism and (2) evidence of endocardial involvement, demonstrated by echocardiographic findings. A positive echocardiographic finding is considered a major criterion.
BOX 19-2
Major Criteria
- A.
Blood culture positive for IE
- 1.
Typical microorganisms consistent with IE from two separate blood cultures: Viridans streptococci, Streptococcus bovis , HACEK group, Staphylococcus aureus ; or community-acquired enterococci in the absence of a primary focus or
- 2.
Microorganisms consistent with IE from persistently positive blood cultures defined as follows: at least two positive cultures of blood samples drawn >12 h apart or all of three or a majority of four or more separate cultures of blood (with first and last sample drawn at least 1 h apart)
- 3.
Single positive blood culture for Coxiella burnetii or anti–phase 1 IgG antibody titer >1:800
- 1.
- B.
Evidence of endocardial involvement
Echocardiogram positive for IE (TEE is recommended for patients with prosthetic valves, rated at least “possible IE” by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients) defined as follows:
- 1.
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
- 2.
Abscess or
- 3.
New partial dehiscence of prosthetic valve or
- 4.
New valvular regurgitation (worsening or changing or preexisting murmur not sufficient)
Minor Criteria
- 1.
Predisposition, predisposing heart condition, or IDU
- 2.
Fever, temperature >38°C
- 3.
Vascular phenomena: major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway’s lesions
- 4.
Immunologic phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor
- 5.
Microbiologic evidence: positive blood culture but does not meet a major criterion as noted above ∗
∗ Excludes single positive cultures for coagulase-negative staphylococci and organisms that do not cause endocarditis.
or serologic evidence of active infection with organism consistent with IE
HACEK, Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, and Kingella spp.; IE, infective endocarditis; IDU, injection drug user; TEE, transesophageal echocardiography; TTE, transthoracic echocardiography.
Definition of Terms Used in the Modified Duke Criteria for the Diagnosis of Infective Endocarditis
Baddour LM, Wilson WR, Bayer AS, et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation 111(23):e394-e433, 2005.
- A.
- a.
- 2.
The category of “ possible” IE is made when one of the following is present:
- a.
One major criterion and one minor criterion
- b.
Three minor criteria
- a.
- 3.
The other category of diagnosis is “rejected” IE, which is made:
- a.
When an alternative diagnosis is established
- b.
When clinical manifestations of IE have resolved within 4 days of antibiotic therapy
- c.
No pathological evidence is found on direct examination of the vegetation obtained from surgery or autopsy after antibiotic therapy for less than 4 days
- d.
When criteria for possible IE are not met
- a.
Definite Infective Endocarditis
- A.
Pathological criteria
- 1.
Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen or
- 2.
Pathological lesions; vegetation or intracardiac abscess confirmed by histologic examination showing active endocarditis
- 1.
- B.
Clinical criteria
- 1.
Two major criteria or
- 2.
One major criterion and three minor criteria or
- 3.
Five minor criteria
- 1.
Possible Infective Endocarditis
- 1.
One major criterion and one minor criterion or
- 2.
Three minor criteria
Rejected
- 1.
Firm alternative diagnosis explaining evidence of IE or
- 2.
Resolution of IE syndrome with antibiotic therapy for <4 days or
- 3.
No pathological evidence of IE at surgery or autopsy with antibiotic therapy for <4 days or
- 4.
Does not meet criteria for possible IE as above
IE, infective endocarditis.
Management
- 1.
Blood cultures are indicated for all patients with fever of unexplained origin and a pathologic heart murmur, a history of heart disease, or previous endocarditis.
- a.
Usually three blood cultures are drawn by separate venipunctures over 24 hours unless the patient is very ill. In 90% of cases, the causative agent is recovered from the first two cultures.
- b.
If there is no growth by the second day of incubation, two more may be obtained. There is no value in obtaining more than five blood cultures over 2 days unless the patient received prior antibiotic therapy.
- c.
It is not necessary to obtain the cultures at any particular phase of the fever cycle.
- d.
Adequate volume of blood must be obtained: 1 to 3 mL in infants and young children and 5 to 7 mL in older children are optimal.
- e.
Aerobic incubation alone suffices because it is rare for IE to be caused by anaerobic bacteria.
- a.
- 2.
It is highly recommended that consultation from a local infectious disease specialist be obtained when IE is suspected or confirmed because antibiotics of choice are continually changing, and there may be special situation pertaining to the local area.
- 3.
Initial empirical therapy is started with the following antibiotics while awaiting the results of blood cultures:
- a.
The usual initial regimen is an antistaphylococcal semisynthetic penicillin (nafcillin, oxacillin, or methicillin) and an aminoglycoside (gentamicin). This combination covers against S. viridans, S. aureus, and gram-negative organisms. Some experts add penicillin to the initial regimen to cover against S. viridans, although a semisynthetic penicillin is usually adequate for initial therapy.
- b.
If a methicillin-resistant S. aureus is suspected, vancomycin should be substituted for the semisynthetic penicillin.
- c.
Vancomycin can be used in place of penicillin or a semisynthetic penicillin in penicillin-allergic patients.
- a.
- 4.
The final selection of antibiotics depends on the organism isolated and the results of an antibiotic sensitivity test.
- a.
Streptococcal IE
- (1)
In general, patients with native cardiac valve IE caused by a highly sensitive S. viridans can be successfully treated with IV penicillin (or ceftriaxone given once daily) for 4 weeks. Alternatively, penicillin, ampicillin, or ceftriaxone combined with gentamicin for 2 weeks may be used.
- (2)
For IE caused by penicillin-resistant streptococci, 4 weeks of penicillin, ampicillin, or ceftriaxone combined with gentamicin for the first 2 weeks is recommended.
- (1)
- b.
Staphylococcal endocarditis
- (1)
The drug of choice for native valve IE by methicillin-susceptible staphylococci is one of the semisynthetic β-lactamase–resistant penicillins (nafcillin, oxacillin, or methicillin) for a minimum of 6 weeks (with or without gentamicin for the first 3–5 days).
- (2)
Patients with methicillin-resistant native valve IE are treated with vancomycin for 6 weeks (with or without gentamicin for the first 3–5 days).
- (1)
- c.
Enterococcus-caused native valve endocarditis usually requires a combination of IV penicillin or ampicillin together with gentamicin for 4 to 6 weeks. If patients are allergic to penicillin, vancomycin combined with gentamicin for 6 weeks is required.
- d.
HACEK organisms have begun to become resistant to ampicillin. Ceftriaxone or another third-generation cephalosporin alone or ampicillin plus gentamicin for 4 weeks is recommended. IE caused by other gram-negative bacteria (such as Escherichia coli , Pseudomonas aeruginosa , or Serratia marcescens ) is treated with piperacillin or ceftazidime together with gentamicin for a minimum of 6 weeks.
- e.
Amphotericin B is the most effective agent for most fungal infections.
- f.
For culture-negative endocarditis, treatment is directed against staphylococci, streptococci, and the HACEK organisms using ceftriaxone and gentamicin. When staphylococcal IE is suspected, nafcillin should be added to the above therapy.
- a.
- 5.
Patients with prosthetic valve endocarditis should be treated for 6 weeks based on the organism isolated and the results of the sensitivity test. Operative intervention may be necessary before the antibiotic therapy is completed if the clinical situation warrants (e.g., progressive CHF, significant malfunction of prosthetic valves, persistently positive blood cultures after 2 weeks of therapy). Bacteriologic relapse after an appropriate course of therapy also calls for operative intervention.
Prognosis
The overall recovery rate is 80% to 85%; it is 90% or better for S. viridans and enterococci and about 50% for Staphylococcus organisms. Fungal endocarditis is associated with a very poor outcome.
Prevention
In 2007, the American Heart Association (AHA) made a major change in the antibiotic prophylaxis against IE ( Wilson et al, 2007 ). The same was recommended jointly by the American College of Cardiology (ACC) and the AHA in 2008 in a focused practice guideline ( Nishimura et al, 2008 ). The following are the main reasons for the change in the long-standing tradition of antibiotic prophylaxis in patients with most of the CHDs.
- 1.
An exceedingly small number of IE that could be caused by bacteremia-producing dental procedures. The estimated frequency of bacteremia during routine daily activities (e.g., chewing, toothbrushing, flossing, used of toothpicks, use of water irrigation devices, and other activities) far exceeds that occurring during dental procedures. For example, tooth brushing and flossing result in bacteremia 20% to 40% of the time and chewing food results in bacteremia 7% to 51% of the time. The cumulative risk over time of bacteremia from routine daily activities is estimated to be greater than 100,000 times compared with that resulting from dental procedures.
- 2.
Besides, the ability of antibiotic therapy to prevent or reduce bacteremia is controversial, and nonfatal adverse reactions (e.g., rash, diarrhea, and GI upset) also occur frequently.
Therefore, an emphasis should be on maintaining good oral hygiene and eradicating dental disease to decrease the frequency of bacteremia from routine daily activities. The new guidelines recommend antibiotic prophylaxis only for cardiac conditions listed in Box 19-3 . Procedures for which antibiotic prophylaxis is recommended and those for which it is not recommended are listed in Box 19-4 . Note that prophylaxis is no longer recommended for routine bronchoscopy; it is recommended for tonsillectomy and adenoidectomy only in high-risk patients (see Box 19-4 ). Prophylaxis is no longer recommended for GI or genitourinary procedures, such as diagnostic esophagogastroduodenoscopy or colonoscopy. Regimens for dental and oral procedures are given in Table 19-1 .
- 1.
Patients with prosthetic cardiac valve or prosthetic material used for cardiac valve repair
- 2.
Patients with previous IE
- 3.
Patients with CHD:
- a.
Unrepaired cyanotic CHD, including palliative shunts and conduits
- b.
Completely repaired CHD with prosthetic material or device, whether placed by surgery or by catheter intervention, during the first 6 months after the procedure ∗
∗ Prophylaxis is recommended because endothelialization of prosthetic material occurs within 6 months after the procedure.
- c.
Repaired CHD with residual defects at the site or adjacent to the site of a prosthetic patch or prosthetic device (which inhibits endothelialization)
- a.
- 4.
Cardiac transplantation recipients with valve regurgitation caused by a structurally abnormal valve
CHD, congenital heart disease; IE, infective endocarditis.
- 1.
Dental procedures
All dental procedures that involve manipulation of gingival tissue of the periapical region of teeth or perforation of the oral mucosa. Antibiotic choices and dosages for dental procedures are shown in Table 19-1 .
- 2.
Respiratory tract procedures
- a.
Prophylaxis is recommended for the procedures that involve incision or biopsy of the respiratory mucosa, such as tonsillectomy and adenoidectomy.
- b.
Prophylaxis is not recommended for bronchoscopy (unless it involves incision of the mucosa, such as for abscess or empyema).
- a.
- 3.
GI or GU procedures
- a.
No prophylaxis is used for diagnostic esophagogastroduodenoscopy or colonoscopy.
- b.
Prophylaxis is reasonable in patients with infected GI or GU tract (with amoxicillin or ampicillin to cover against enterococci).
- a.
- 4.
Skin, skin structure, or musculoskeletal tissue
- a.
Prophylaxis is recommended for surgical procedures that involve infected skin, skin structure, or musculoskeletal tissue (with antibiotics against staphylococcus and ß-hemolytic streptococcus, such as antistaphylococcal penicillin or a cephalosporin).
- b.
Vancomycin or clindamycin is administered if unable to tolerate ß-lactam or if infection is caused by methicillin-resistant staphylococcus.
- a.
GI, gastrointestinal; GU, genitourinary.
| Situation | Agent | Single Dose 30–60 min Before Procedure | |
|---|---|---|---|
| Children | Adults | ||
| Oral | Amoxicillin | 50 mg/kg | 2 g |
| Unable to take oral medications | Ampicillin or | 50 mg/kg (IM, IV) | 2 g (IM, IV) |
| Cefazolin or ceftriaxone | 50 mg/kg (IM, IV) | 1 g (IM, IV) | |
| Allergic to penicillin or ampicillin—oral | Cephalexin ∗ † or | 50 mg/kg | 2 g |
| Clindamycin, or | 20 mg/kg | 600 mg | |
| Azithromycin or | 15 mg/kg | 500 mg | |
| Clarithromycin | 15 mg/kg | 500 mg | |
| Allergic to penicillin or ampicillin and unable to take oral medication | Cefazolin or ceftriaxone | 50 mg/kg (IM, IV) | 1 g (IM, IV) |
| Clindamycin | 20 mg/kg | 600 mg | |
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