2: Infective Endocarditis

Chapter 2

Infective Endocarditis

Infective endocarditis (IE) is a microbial infection of the endothelial surface of the heart or heart valves that most often occurs in proximity to congenital or acquired cardiac defects.< ?xml:namespace prefix = "mbp" />1 A clinically and pathologically similar infection that may occur in the endothelial lining of an artery, usually adjacent to a vascular defect (e.g., coarctation of the aorta) or a prosthetic device (e.g., arteriovenous [AV] shunt), is called infective endarteritis. Although bacteria most often cause these diseases, fungi and other microorganisms also may cause such infection; thus, the designation infective is used in keeping with this multimicrobial origin. The term bacterial endocarditis (BE) is in common use, reflecting the fact that most cases of IE are due to bacteria; however, IE has become the preferred nomenclature and is therefore used in this chapter.

Previously, IE was classified as acute or subacute, to reflect the rapidity of onset and duration of symptoms before diagnosis; however, this classification was found to be somewhat arbitrary. It has now largely been replaced by a classification that is based on the causative microorganism (e.g., streptococcal endocarditis, staphylococcal endocarditis, candidal endocarditis) and the type of valve that is infected (e.g., native valve endocarditis [NVE], prosthetic valve endocarditis [PVE]). IE also is classified according to the source of infection—that is, whether it is community-acquired or hospital-acquired—or whether the patient is an intravenous drug user (IVDU).

IE is a disease of significant morbidity and mortality that is difficult to treat; therefore, emphasis has long been directed toward prevention. Historically, various dental procedures have been reported to be a significant cause of IE, because bacterial species found in the mouth frequently have been found to be the causative agent. Furthermore, whenever a patient is given a diagnosis of IE caused by oral flora, dental procedures performed at any point within the previous several months typically have been blamed for the infection. As a result, antibiotics have been administered before certain invasive dental procedures in an attempt to prevent infection. Of note, however, the effectiveness of such prophylaxis in humans has never been substantiated, and accumulating evidence more and more questions the validity of this practice.


IE is a serious, life-threatening disease that affects more than 15,000 patients each year in the United States; the overall mortality rate approaches 40%.2 IE is a relatively rare disease that occurs most frequently in middle-aged and elderly persons and is more common in men than in women. The incidence rate varies with the population studied. In the general population, the incidence has remained relatively stable over the past 3 decades, ranging between 0.16 and 5.4 cases per 100,000 person-years.3 A somewhat higher incidence has been reported, however, in more recent studies. A community study in Minnesota reported an incidence of 5 to 7 cases per 100,000 person-years, and a study in the metropolitan Philadelphia area reported an overall incidence of 11.6 per 100,000 person-years.4,5 In the Philadelphia study, the rate of community-acquired IE was found to be 4.45 per 100,000 person-years, which is comparable to that reported in previous studies; however, the higher overall incidence was attributed to a high prevalence of intravenous drug users (IVDUs) in the population studied.

When populations at enhanced risk are considered, the incidence rate is increased. One study reported the lifetime risk of acquiring IE with various conditions.6 In that study, the risk ranged from 5 per 100,000 person-years in the general population to 2160 per 100,000 person-years in patients who underwent surgical replacement of an infected prosthetic valve (Table 2-1). Previously, the most common underlying condition predisposing to endocarditis was rheumatic heart disease (RHD) (Figure 2-1); however, in developed countries, the frequency of RHD has markedly declined over the past several decades, and this disorder has become a much less significant factor. Mitral valve prolapse (MVP) (Figure 2-2), which accounts for 25% to 30% of adult cases of NVE, is now the most common underlying condition among patients who acquire IE.5 Aortic valve disease (either stenosis or regurgitation or both) (Figure 2-3) appears to account for about 30% of cases.7 Congenital heart disease (e.g., patent ductus arteriosus, ventricular septal defect, bicuspid aortic valve) (Figure 2-4) is the substrate for IE in 10% to 20% of younger adults and in 8% of older adults.1 Tetralogy of Fallot, the most common type of congenital cyanotic heart disease, generally requiring extensive reconstructive surgery for survival (Figure 2-5), accounts for less than 2% of cases. The incidence of PVE (Figure 2-6) is increasing, and this entity accounts for about one third of all cases of IE. Of note, in many patients with IE, a predisposing cardiac condition cannot be identified (Table 2-2).

TABLE 2-1 Lifetime Risk of Acquiring Infective Endocarditis

Predisposing Condition/Factor No. of Patients/100,000 Patient-Years
General population 5
Mitral valve prolapse without audible cardiac murmur 4.6
Mitral valve prolapse with audible murmur of mitral regurgitation 52
Rheumatic heart disease 380-440
Mechanical or bioprosthetic valve 308-383
Cardiac valve replacement surgery for native valve 630
Previous endocarditis 740
Prosthetic valve replacement in patients with PVE 2160

PVE, prosthetic valve endocarditis.

Data from Steckelberg JM, Wilson WR: Risk factors for infective endocarditis, Infect Dis Clin North Am 7:9-19, 1993.


FIGURE 2-1 Mitral stenosis with diffuse fibrous thickening and distortion of the valve leaflets in chronic rheumatic heart disease.

(From Schoen FJ, Mitchell RN: The heart. In Kumar V, et al, editors: Robbins and Cotran pathologic basis of disease, ed 8, Philadelphia, 2010, Saunders.)


FIGURE 2-2 Prolapse of the posterior mitral valve leaflet into the left atrium.

(Courtesy William D. Edwards, MD, Mayo Clinic, Rochester, Minnesota. From Schoen FJ, Mitchell RN: The heart. In Kumar V, et al, editors: Robbins and Cotran pathologic basis of disease, ed 8, Philadelphia, 2010, Saunders.)


FIGURE 2-3 Calcific aortic stenosis of a previously normal valve. Nodular masses of calcium are heaped up within the sinuses of Valsalva.

(From Schoen FJ, Mitchell RN: The heart. In Kumar V, et al, editors: Robbins and Cotran pathologic basis of disease, ed 8, Philadelphia, 2010, Saunders.)


FIGURE 2-4 Gross photograph of a ventricular septal defect (defect denoted by arrow).

(Courtesy William D. Edwards, MD, Mayo Clinic, Rochester, Minnesota. From Schoen FJ, Mitchell RN: The heart. In Kumar V, et al, editors: Robbins and Cotran pathologic basis of disease, ed 8, Philadelphia, 2010, Saunders.)


FIGURE 2-5 Tetralogy of Fallot. 1, Pulmonary stenosis. 2, Ventricular septal defect. 3, Overriding aorta. 4, Right ventricular hypertrophy. Ao, Aorta; LA, left atrium; LV, left ventricle; PA, pulmonary artery; RA, right atrium; RV, right ventricle.

(Redrawn from Mullins CE, Mayer DC: Congenital heart disease: a diagrammatic atlas, New York, 1988, Wiley-Liss.)


FIGURE 2-6 Prosthetic cardiac valves.

A, Starr-Edwards caged ball mechanical valve. B, Hancock porcine bioprosthetic valve. C, Prosthetic valve endocarditis.

TABLE 2-2 Predisposing Conditions Associated with Infective Endocarditis (IE)

Underlying Condition Frequency of IE
Mitral valve prolapse 25-30%
Aortic valve disease 12-30%
Congenital heart disease 10-20%
Prosthetic valve 10-30%
Intravenous drug abuse 5-20%
No identifiable condition 25-47%

The incidence of IE among IVDUs ranges from 150 to 2000 per 100,000 person-years.8 Conversely, among patients with IE, the concomitant rate of intravenous drug abuse ranges from 5% to 20%.9 Several unique features characterize the IE in IVDUs. In most cases, the cardiac valves are normal before infection. Such infection usually affects the valves of the right side of the heart (tricuspid), and Staphylococcus aureus is the most common pathogen.10 Thus, because of these unique characteristics, IE in IVDUs historically has not been linked to dental treatment.


About 90% of community-acquired cases of native valve IE are due to streptococci, staphylococci, or enterococci, with streptococci being the most common causative organisms.3 In IE associated with intravenous drug abuse or secondary to health care contact, staphylococci are the most common pathogen identified. Overall, streptococci continue to be the most common cause of IE, but staphylococci have been gaining increasing importance. Viridans streptococci (α-hemolytic streptococci), constituents of the normal oral flora and gastrointestinal (GI) tract, remain the most common cause of community-acquired NVE, without regard for intravenous drug abuse, and they cause 30% to 65% of cases of IE.1 The species that most commonly cause endocarditis are Streptococcus sanguis, Streptococcus oralis (mitis), Streptococcus salivarius, Streptococcus mutans, and Gemella morbillorum (formerly called Streptococcus morbillorum). Group D streptococci, which include Streptococcus bovis and the enterococci (Enterococcus faecalis), are normal inhabitants of the GI tract and account for 5% to 18% of cases of IE. Streptococcus pneumoniae has decreased in prevalence and now accounts for only 1% to 3% of cases of IE.11 Group A β-hemolytic streptococci rarely cause IE.1

Staphylococci are the cause of at least 30% to 40% of cases of IE; of these, 80% to 90% are due to coagulase-positive S. aureus.2 S. aureus, the cause of most cases of acute IE, is the most common pathogen in IE associated with intravenous drug abuse. It also is the most common pathogen in nonvalvular cardiovascular device infections.12 Of note, S. aureus is not a normal constituent of the oral flora. In PVE, staphylococci are the most common pathogens in early and intermediate infections; however, streptococci predominate in late PVE. The proportion of cases of S. aureus–related IE appears to be increasing at community-based and university hospitals. This increase appears to be due in large part to increasing health care contact, such as through surgical procedures or the use of indwelling catheters.

Other microbial agents that less commonly cause IE include the HACEK group (Haemophilus, Actinobacillus, Cardiobacterium, Eikenella, Kingella), Pseudomonas aeruginosa, Corynebacterium pseudodiphtheriticum, Listeria monocytogenes, Bacteroides fragilis, and fungi.

Pathophysiology and Complications

Although the precise mechanism whereby IE occurs has not been fully elucidated, it is thought to be the result of a series of complex interactions of several factors involving endothelium, bacteria, and the host immune response. The sequence of events leading to infection usually begins with injury or damage to an endothelial surface, most often of a cardiac valve leaflet. Although IE can occur on normal endothelium, most cases begin with a damaged surface, usually in proximity to an anatomic defect or prosthesis. Endothelial damage can result from any of a variety of events, including the following1:

Directed flow from a high-velocity jet onto the endothelium

Flow from a high- to a low-pressure chamber

Flow across a narrowed orifice at high velocity

Fibrin and platelets then adhere to the roughened endothelial surface, where they form small clusters or masses, resulting in a condition called nonbacterial thrombotic endocarditis (NBTE) (Figure 2-7). A similar and frequently indistinguishable condition is found in some patients with systemic lupus erythematosus and is called Libman-Sacks verrucous endocarditis. Initially, these masses are sterile and do not contain microorganisms. With the occurrence of a transient bacteremia, however, bacteria can be seeded into and adhere to the mass. Additional platelets and fibrin are then deposited onto the surface of the mass, which serves to sequester and protect the bacteria, which undergo rapid multiplication within the protection of the vegetative mass (Figure 2-8). Once the vegetative process is established, the metabolic activity and cellular division of the bacteria are diminished, which decreases the effectiveness of antibiotics. Bacteria are slowly and continually released from the vegetations and shed into the bloodstream, resulting in a continuous bacteremia; fragments of the friable vegetations break off and embolize. A variety of host immune responses to bacteria may occur. This sequence of events results in the clinical manifestations of IE.


FIGURE 2-7 Nonbacterial thrombotic endocarditis (NBTE).

(From Schoen FJ, Mitchell RN: The heart. In Kumar V, et al, editors: Robbins and Cotran pathologic basis of disease, ed 8, Philadelphia, 2010, Saunders.)


FIGURE 2-8 Viridans streptococcal endocarditis of mitral valve.

(Courtesy W. O’Conner, MD, Lexington, Kentucky.)

The clinical outcome of IE depends on several factors, including1

Local destructive effects of intracardiac (valvular) lesions

Embolization of vegetative fragments to distant sites, resulting in infarction or infection

Hematogenous seeding of remote sites during continuous bacteremia

Antibody response to the infecting organism, with subsequent tissue injury caused by deposition of pre-formed immune complexes or antibody-complement interaction with antigens deposited in tissues

Although combination antibiotic and surgical treatment is effective for many patients, complications are common and serious. The most common complication of IE, and the leading cause of death, is heart failure, which results from severe valvular dysfunction. This pathologic process most commonly begins as a problem with aortic valve involvement, followed by mitral and then tricuspid valve infection. Embolization of vegetation fragments often leads to further complications such as stroke. Myocardial infarction can occur as the result of embolism of the coronary arteries, and distal emboli can produce peripheral metastatic abscesses. Pulmonary emboli, usually septic in nature, occur in 66% to 75% of IVDUs who have tricuspid valve endocarditis.10 Emboli also may involve other systemic organs, including the liver, spleen, and kidney, as well as abdominal mesenteric vessels. The incidence of embolic events is markedly reduced by the initiation of antibiotic therapy.1 Renal dysfunction also is common and may be due to immune complex glomerulonephritis or infarction.13

Signs and Symptoms

The classic findings in IE include fever, heart murmur, and positive blood culture, although the clinical presentation may vary. Of particular significance is that the interval between the presumed initiating bacteremia and the onset of symptoms of IE is estimated to be less than 2 weeks in more than 80% of patients with IE.1,14 In many cases of IE that have been purported to be due to dentally induced bacteremia, the interval between the dental appointment and the diagnosis of IE has been much longer than 2 weeks (sometimes months), so it is very unlikely that the initiating bacteremia was associated with dental treatment.

Fever, the most common sign of IE, occurs in up to 80% to 95% of patients.3 It may be absent, however, in the elderly or in patients with heart failure or renal failure. New or changing heart murmurs, systolic or diastolic, are found in 80% to 85% of patients.1 Heart murmurs often are not heard initially in patients who are IVDUs but appear later in the course of the disease. This sequence is characteristic of tricuspid valve IE caused by S. aureus. Peripheral manifestations of IE due to emboli and/or immunologic responses are less frequently seen since the advent of antibiotics. These include petechiae of the palpebral conjunctiva, the buccal and palatal mucosa, and extremities (Figure 2-9), Osler’s nodes (small, tender, subcutaneous nodules that develop in the pulp of the digits) (Figure 2-10), Janeway lesions (small, erythematous or hemorrhagic, macular nontender lesions on the palms and soles), splinter hemorrhages in the nail beds (Figure 2-11), and Roth spots (oval retinal hemorrhages with pale centers) (Figure 2-12). Other signs include splenomegaly and clubbing of the digits (Figure 2-13). Sustained bacteremia is typical of IE, and blood cultures are positive in most cases. Although up to 30% of cases of IE initially are found to be “culture-negative,” when strict diagnostic criteria are used, only 5% of cases are culture-negative.15 Many patients with negative blood cultures have taken antibiotics before the diagnosis of IE. Three separate sets of blood cultures obtained over a 24-hour period are recommended in the evaluation of a patient for suspected IE.16


FIGURE 2-9 Petechiae in infective endocarditis.

(From Fowler VG Jr, Bayer AS: Infective endocarditis. In Goldman L, Ausiello D, editors: Cecil medicine, ed 23, Philadelphia, 2008, Saunders.)


FIGURE 2-10 Osler’s node in infective endocarditis.

(From Fowler VG Jr, Bayer AS: Infective endocarditis. In Goldman L, Ausiello D, editors: Cecil medicine, ed 23, Philadelphia, 2008, Saunders.)


FIGURE 2-11 Splinter hemorrhages of the nail beds in infective endocarditis.

(From Porter SR, et al: Medicine and surgery for dentistry, ed 2, London, 1999, Churchill Livingstone.)


FIGURE 2-12 A Roth spot in the retina in infective endocarditis.

(From Forbes CD, Jackson WF: Color atlas and text of clinical medicine, ed 3, Edinburgh, 2003, Mosby.)


FIGURE 2-13 Nail clubbing may appear within a few weeks of development of IE.

(From Zipes DP, et al, editors: Braunwald’s heart disease: a textbook of cardiovascular medicine, ed 7, Philadelphia, 2005, Saunders.)

The diagnosis of IE should be considered for a patient with fever along with one or more of the following cardinal elements of IE: a predisposing cardiac lesion or behavior pattern, bacteremia, embolic phenomena, and evidence of an active endocardial process.1 The clinical presentation in IE is variable, and other conditions can cause similar signs and symptoms. The Duke criteria were developed and later modified to facilitate the definitive diagnosis of IE.16,17 Application of this set of diagnostic criteria involves ascertaining the presence or absence of major and minor criteria.

Major criteria are two of the aforementioned cardinal elements:

Positive blood cultures

Evidence of endocardial involvement (e.g., positive findings on echocardiography, presence of new valvular regurgitation)

Minor criteria include the following factors:

Predisposing heart condition or IV drug use


Vascular phenomena including embolic events

Immunologic phenomena

Microbiologic evidence other than positive blood culture

Definitive diagnosis of IE requires the presence of two major criteria, one major and three minor criteria, or five minor criteria.

Laboratory Findings

Other than blood culturing, laboratory tests used for the diagnosis and treatment of IE are basic and nonspecific and may include a complete blood count with differential, electrolyte panel, renal function tests, urinalysis, plain chest radiograph, and electrocardiogram (ECG).1,3 Patients with IE frequently are found to have a normocytic, normochromic anemia that tends to worsen as the disease progresses. The white blood cell count may or may not be elevated. Urinalysis often reveals microscopic hematuria and proteinuria. Appearance on the chest film may be abnormal with evidence of heart failure. ECG may show evidence of conduction block with myocardial involvement or infarction. Other abnormal findings may include an elevated erythrocyte sedimentation rate, increased immune globulins, circulating immune complexes, and positive rheumatoid factor.

Echocardiography, transthoracic or transesophageal, is used to confirm the presence of vegetation in patients suspected of having IE; it has become a cornerstone in the diagnostic process. Echocardiographic evidence of vegetation is one of the major findings included in the Duke criteria.

Medical Management

Before the advent of antibiotics, IE almost always was fatal. This poor outcome has changed dramatically with early diagnosis and the institution of antibiotic therapy or surgical treatment, or both. Although the survival rate has greatly improved, the overall mortality rate still hovers around 40%.2 However, the mortality rate varies significantly among groups of patients with IE of differing causes. For example, for viridans group streptococcal PVE, the reported mortality rate is approximately 20%, but that for viridans group streptococcal NVE is 5% or less.11 For S. aureus endocarditis in non-IVDU patients, the mortality rate ranges between 25% and 40%, and for fungal endocarditis, the mortality rate exceeds 80%. For IE of the tricuspid valve in IVDUs, the mortality rate is between 2% and 4%.10 The management of patients with IE requires effective antibiotic therapy and, in cases involving significant structural damage, surgical intervention.

Recently, guidelines for the diagnosis, antimicrobial therapy, and management of infective endocarditis have been revised as an American Heart Association (AHA) Scientific Statement.11 Most strains of viridans streptococci, “other” streptococci (including Streptococcus pyogenes), and nonenterococcal group D streptococci (primarily S. bovis) are exquisitely sensitive to penicillins, with a minimal inhibitory concentration (MIC) of less than 0.2 µg/mL. Bacteriologic cure rates of 98% or higher may be anticipated in patients who complete 4 weeks of therapy with parenteral penicillin or ceftriaxone for NVE caused by highly penicillin-susceptible viridans group streptococci or S. bovis. The addition of gentamicin sulfate to penicillin exerts a synergistic killing effect on viridans group streptococci and S. bovis. A 2-week regimen of penicillin or ceftriaxone combined with single-daily-dose gentamicin is appropriate for uncomplicated cases of endocarditis caused by highly penicillin-susceptible viridans group streptococci or S. bovis in patients at low risk for adverse events caused by gentamicin therapy. For patients who are unable to tolerate penicillin or ceftriaxone, vancomycin is the most effective alternative.

Patients with endocarditis arising as a complication after surgery to place prosthetic valves or other prosthetic material that is caused by a highly penicillin-susceptible strain (MIC of 0.12 µg/mL or less) should receive 6 weeks of therapy with penicillin or ceftriaxone, with or without gentamicin for the first 2 weeks. Those with endocarditis caused by a strain that is relatively or highly resistant to penicillin (MIC greater than 0.12 µg/mL) should receive 6 weeks of therapy with penicillin or ceftriaxone combined with gentamicin. Vancomycin therapy is recommended only for patients who are unable to tolerate penicillin or ceftriaxone.

Regardless of whether IE is community- or hospital-acquired, most S. aureus organisms produce β-lactamase; therefore, the condition is highly resistant to penicillin G. The drug of choice for treatment of IE caused by methicillin-susceptible S. aureus (MSSA) is one of the semisynthetic, penicillinase-resistant penicillins such as nafcillin or oxacillin sodium. For patients with native valve S. aureus endocarditis, a 6-week course of oxacillin or nafcillin with the optional addition of gentamicin for 3 to 5 days is recommended. Staphylococcal PVE is treated as for NVE, except that treatment is given for a longer period. For strains resistant to oxacillin, vancomycin is combined with rifampin and gentamicin.

Surgical intervention may be necessary to facilitate a cure for IE or to repair damage caused by the infection. Indications for surgery include moderate to severe heart failure caused by valvular dysfunction, unstable or obstructed prosthesis, infection uncontrollable by antibiotics alone, fungal endocarditis, and intracardiac complications with PVE.


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Jan 4, 2015 | Posted by in General Dentistry | Comments Off on 2: Infective Endocarditis

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