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Infective endocarditis (IE) is a microbial infection of the heart valves or
other endocardial tissue, usually associated with an underlying cardiac
defect. Disease incidence has remained stable over time accounting for
15,000 to 20,000 new cases per year. Streptococcus viridans,
Staphylococcus aureus, and Enterococcus species are common causes
of IE. Other rare pathogens affecting special populations include
Staphylococcus epidermidis, Pseudomonas aeruginosa, and Candida
Clinical presentation may be highly variable and characterized by
nonspecific symptoms such as fever, weight loss, fatigue, night sweats,
and arthralgias. Peripheral manifestations specific to IE include
conjunctival petechiae, Janeway lesions, and splinter hemorrhages.
Major embolic episodes and infarction involving other organs can
develop in up to one-third of cases. Congestive heart failure (CHF) is
the most common cause of death in IE, and the most common indication
The American Heart Association (AHA) recommends use of the
modified Duke criteria as the primary diagnostic schema to evaluate
patients suspected of IE. The most important factor confirming IE is
positive blood cultures. Transesophageal echocardiogram (TEE) is a
valuable tool to strengthen diagnosis and identify patients at risk for
complications and need for surgical interventions.
General treatment approach to organism eradication requires the
administration of parenteral bactericidal antibiotics at high doses for a
prolonged duration of 4 to 6 weeks. Combination therapy may be
needed to achieve synergy for some pathogens. Selection of regimen
should be based on organism sensitivity, tissue penetration, and host
tolerance of the antibiotic agent(s). The AHA treatment guideline by
Treatment of IE caused by methicillin-resistant Staphylococcus aureus
(MRSA) and by enterococci presents significant challenges owing to
emergence of resistance to standard therapy, vancomycin. Higher doses
of vancomycin targeting a trough concentration of 15 to 20 mcg/mL are
advocated for treatment of MRSA IE, but may be associated with
increased incidence of nephrotoxicity. Alternative agents for treatment
of IE caused by vancomycin-resistant enterococci have limited clinical
success or lack of clinical evidence.
Fungal endocarditis is rare, but carries poor prognosis. It occurs primarily
in intravenous (IV) drug users, patients with prosthetic heart valves or
IV catheters, and those with a compromised immune system.
Management generally requires early valve replacement and
combination antifungal therapy.
The AHA recommends the use of antibiotic prophylaxis in select
patients with specific cardiac conditions associated with the highest risk
of adverse outcomes from endocarditis, who are undergoing dental or
respiratory procedures known to cause significant bacteremia.
Antimicrobial prophylaxis should be directed against the viridans group
IE is a microbial infection of the heart valves or other endocardial tissue, often
associated with an underlying cardiac defect. IE is classified based on the causative
organism to provide information on the probable cause and course of the disease
(acute or subacute), the likelihood of underlying heart disease, and the appropriate
The pathogenesis of endocarditis involves a complex series of events that ultimately
result in the formation of an infected platelet-β-fibrin thrombus on the valve
2 This thrombus is called a vegetation.
The first step in the formation of the vegetation involves modification of the
endocardial surface, which is normally nonthrombogenic.
Valvular insufficiency caused by aortic stenosis or ventricular septal defects can
produce regurgitant blood flow, high-pressure gradients, or narrow orifices, resulting
in turbulence and endocardial damage.
In patients with rheumatic heart disease,
endocardial injury (e.g., mitral valve stenosis) occurs as a result of immune complex
deposition or hemodynamic disturbances.
Once the endocardial surface of the valve is traumatized, small, sterile thrombi
consisting of platelets and fibrin are deposited, forming the lesion called
nonbacterial thrombotic endocarditis (NBTE).
2 NBTE occurs most commonly on
the atrial surfaces of the mitral and tricuspid valves and on the ventricular surface of
NBTE serves as a nidus for microbial colonization during periods of bacteremia
(e.g., procedures involving perforation of the oral mucosa, respiratory tract,
genitourinary tract, or infected skin). Organisms such as Streptococcus viridans
group, Enterococcus species, Staphylococcus aureus, Staphylococcus epidermidis,
Pseudomonas aeruginosa, and Candida albicans possess adherence factors that
facilitate their pathogenicity. In particular, platelet aggregation has been shown to be
an important virulence factor in experimental streptococcal endocarditis potentially
leading to larger vegetations and multifocal embolic spread.
becomes colonized by microorganisms, the surface is rapidly covered with a sheath
of fibrin and platelets. This avascular encasement provides an environment protected
from host defenses and is conducive to further bacterial replication and vegetation
2 The bacterial colony count can be as high as 10
Endocarditis can result in life-threatening hemodynamic disturbances and embolic
episodes affecting many organs. Without antimicrobial therapy and surgical
intervention, IE is virtually 100% fatal. Because of bacterial proliferation to high
densities in the fibrin mesh protected from normal host defenses, cure of infection
requires prolonged therapy of 4 to 6 weeks with relapse not uncommon.
In 2009, there were 38,976 hospital admissions of endocarditis with an hospital
5 The overall incidence has been stable; however,
health–care-associated IE has emerged as a result of increased use of invasive
medical devices and procedures (e.g., IV catheters, total parenteral nutrition [TPN]
IV lines, hemodialysis shunts or fistulas, intracardiac prosthesis, central venous
1 With the exception of IV drug users, the mean patient age
has shifted from younger than 30 years in the 1920s to older than 55 years today.
This increase in age is likely attributable to (a) a decline in the incidence of acute
rheumatic fever and rheumatic heart disease counterbalanced by degenerative
valvular disease in an increasing elderly population, (b) the increasing longevity of
the general population, and (c) increased exposure to more intense and invasive
medical procedures in both the overall and the aging populations. Men are infected
more often than women (roughly 2:1), and the disease remains uncommon in children,
primarily in association with underlying congenital cardiac defect and nosocomial
In general, any structural cardiac defect that leads to the turbulence of blood flow
predisposes to the development of IE. Rheumatic heart disease was at one time the
most common underlying cardiac defect associated with endocarditis; however, the
proportion of cases related to rheumatic heart disease have declined to 25% or less
in developed countries while remaining the predominant defect in developing
5 Mitral valve prolapse with thickened leaflets and valvular redundancy is
a recognized predisposing risk to IE, with a documented occurrence rate of 10%.
Clinical presentation is often subtle with lower associated mortality in these
individuals compared with left-sided IE of other types. In the absence of underlying
valvular defects, degenerative cardiac lesions, such as calcified mitral annulus
secondary to atherosclerotic cardiovascular disease and postmyocardial infarction
thrombus, may be a significant risk factor for the elderly. IV drug users constitute a
unique population at greatest risk for recurrent and polymicrobial IE.
Hemodialysis dependency (8%), diabetes mellitus (16%), and congenital heart
disease (12%) are the most common demographic characteristics associated with
7 Up to 25% of all cases are acquired in health-care-related settings. Notably, in
the United States, health-care-associated IE is more likely compared with community
Streptococci and staphylococci are the cause of 80% to 90% of cases of IE. When
comparing epidemiologic studies in the aggregate during the past decades,
staphylococci are increasingly prevalent as a cause of IE. Viridans streptococci
remain the predominant cause of IE in children and in young women with isolated
Staphylococcus aureus is the leading cause of IE.
8 Acquisition of IE in nearly half
of these cases was likely health-care-related, supporting a low threshold to evaluate
underlying IE in the setting of health-care-related S. aureus bacteremia. More
importantly, methicillin-resistant strains account for up to 40% of IE cases involving
Endocarditis in IV drug users often is caused by S. aureus, whereas prosthetic
valve endocarditis (PVE) is more commonly caused by coagulase-negative
staphylococci, such as S. epidermidis. Gram-negative bacilli and fungi together
account for less than 10% of all endocarditis cases, which usually are associated
with IV drug use, valvular prostheses, and hospital IV access procedures.
Endocarditis caused by anaerobes and other organisms is rare. Polymicrobial IE
(caused by at least two organisms), although uncommon in the typical patient, is
being recognized more frequently in IV drug users and certain postoperative patients.
Candida species, S. aureus, P. aeruginosa, Serratia marcescens, and non-β hemolytic
group D streptococci are the organisms involved most frequently in these
The site of heart valve involvement is determined by the underlying cardiac defect
7 The mitral valve is affected in more than 85% of
cases caused by viridans streptococci with underlying rheumatic heart disease. The
tricuspid valve is the common site of involvement in staphylococcal endocarditis
associated with IV drug use. Overall, the distribution ranges from 28% to 45% for
mitral valve, 5% to 36% for aortic valves, and 0% to 6% for tricuspid valves, and
the pulmonary valve is rarely affected.
9 Multiple heart valves may be affected
simultaneously. Some studies have shown that aortic valve involvement is increasing
in frequency and is associated with higher morbidity and mortality.
Relevant laboratory results include the following:
Hemoglobin (Hgb), 11.4 g/dL (SI units, 114 g/L [normal, 140–180])
Hematocrit (Hct), 34% (SI units, 0.34 [normal, 0.39–0.49])
Reticulocyte count, 0.5% (SI units, 0.005 [normal, 0.001–0.024])
and 0.01 bands [normal, 3.2–9.8 with 0.54–0.62 polys and 0.03–0.05 bands])
Blood urea nitrogen (BUN), 21 mg/dL (SI units, 7.5 mmol/L of urea [normal, 2.9–8.9])
Serum creatinine (SCr), 1.2 mg/dL (SI units, 159 mmol/L [normal, 53–133])
The erythrocyte sedimentation rate (ESR) is elevated at 66 mm/hour (normal, ≤30 mm/minute), and the
units/day), and IV gentamicin, 120 mg (loading dose) followed by 60 mg every 12 hours. Antimicrobial
The clinical presentation of IE is highly variable and can involve almost any organ
1 A.G. appears pale and chronically ill, and represents the typical patient with
subacute disease (e.g., that caused by viridans streptococci). Nonspecific complaints
consistent with endocarditis in A.G. include fatigue, weight loss, fever, night sweats,
and arthralgias. Fever alone is present in most (90%) patients with endocarditis. The
fever is characteristically low grade and remittent, with peaks in the afternoon and
evening. Fever may be absent or minimal in patients with CHF, chronic renal and
liver failure, prior use of antimicrobial agents, or IE caused by less virulent
1 Musculoskeletal complaints (e.g., arthralgias, myalgias, and back pain)
are common and may mimic rheumatic disease. Other symptoms can include lethargy,
anorexia, malaise, nausea, and vomiting.
1 Because signs and symptoms are
nonspecific and subtle, diagnosis is often difficult to make. In addition, the time from
bacteremia to diagnosis is often prolonged because of the insidious progression of
1 Delayed diagnosis occurs more commonly in the elderly. Fever may be
absent in 30% to 40% of patients older than 60 years of age, whereas it can be
present in more than 90% of patients younger than 40 years of age. Elderly patients
are less likely to have new or changed heart murmurs. The most common presenting
complaints in the elderly with endocarditis are confusion, anorexia, fatigue, and
weakness, which may be readily attributable to stroke, heart failure, or syncope.
The temporal relationship between A.G.’s dental procedure and the onset of
symptoms suggests it was the etiology of bacteremia and subsequent endocarditis.
Although it is assumed that prophylactic antibiotics were administered before the
procedure, endocarditis can develop despite receipt of adequate
A.G. has an increase in his preexisting diastolic murmur with mitral insufficiency,
a finding consistent with endocarditis. Cardiac murmurs are present in more than
85% of patients with endocarditis. Murmurs frequently are absent in patients with
acute disease (e.g., staphylococcal endocarditis), right-sided disease (e.g.,
endocarditis in IV drug users), or mural infection.
A.G. exhibits several peripheral manifestations of IE, including conjunctival
petechiae, Janeway lesions, and splinter hemorrhages. Overall, peripheral
manifestations are observed in 10% to 50% of cases, but none of these is
1 These manifestations are usually a result of septic
embolization of vegetations to distal sites, or immune complex deposition.
Mucocutaneous petechial lesions of the conjunctiva, mouth, or pharynx are present in
20% to 40% of patients, especially those with long-standing disease.
generally are small, nontender, and hemorrhagic in appearance, and occur as a result
of vasculitis or peripheral embolization. Janeway lesions are painless, hemorrhagic,
macular plaques most commonly found on the palms and soles (Fig. 66-1). Splinter
hemorrhages are nonspecific findings that appear as red to brown linear streaks in the
proximal portion of the fingers or toenails (Fig. 66-2). Other findings can include
Roth spots (small, flame-shaped retinal hemorrhages with pale white centers found
near the optic nerve) and Osler nodes (purplish, nonhemorrhagic, painful nodules that
develop on the subcutaneous pads of the fingers and toes or on palms and soles)
Clubbing (broadening and thickening) of the nails also may be observed in patients
with prolonged disease. Petechial skin lesions also are seen (Fig. 66-3).
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