Infective endocarditis in children

INTRODUCTION — 

Infective endocarditis (IE) is an infection of the endocardium and/or heart valves that involves thrombus formation (vegetation), which may damage the endocardial tissue and/or valves. The process can involve native endocardium/endothelium or prosthetic material. Although uncommon in children, it is important to identify and treat IE because of its significant morbidity and mortality. Prompt diagnosis, rapid treatment, and recognition of complications are imperative for optimal patient outcomes.

IE is also referred to as bacterial endocarditis because bacteria are the predominant microbial pathogens. IE is used in this review to include both bacterial and fungal endocarditis.

Many aspects of IE are similar in children and adults, but there are some manifestations that are unique to children.

An overview of IE in children is presented here. Related topics include:

●Antibiotic prophylaxis of IE (see "Prevention of endocarditis: Antibiotic prophylaxis and other measures")

●Antimicrobial therapy for IE (see "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis")

●Complications and outcome of IE (see "Complications and outcome of infective endocarditis")

●Diagnostic criteria and approach for IE (see "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on '2023 Duke-ISCVID criteria')

●Epidemiology, risk factors and microbiology of IE (see "Native valve endocarditis: Epidemiology, risk factors, and microbiology")

●Role of echocardiography in the diagnosis of IE (see "Role of echocardiography in infective endocarditis")

●Surgery for IE (see "Surgery for left-sided native valve infective endocarditis" and "Prosthetic valve endocarditis: Surgical management")

EPIDEMIOLOGY

Incidence — Reported incidence rates of pediatric IE in the United States range from 0.3 to 3.3 per 100,000 individuals per year [1-3]. Rates are higher among infants <1 year old compared with older children and adolescents.

The most important risk factor for IE in childhood is congenital heart disease (CHD) [4,5]. In one study, the estimated cumulative risk of IE by age 18 years among children with CHD was 0.6 percent [4].

Rates of pediatric IE increased during the latter half of the twentieth century, likely due to dramatic improvements in survival of children with CHD and increased use of central venous catheters (CVCs) [6,7]. Since the early 2000s, rates of IE appear to have plateaued or slightly decreased [1,2,8]. Studies evaluating pediatric hospital admission rates for IE in the United States before and after publication of the 2007 revised antibiotic prophylaxis guidelines did not detect a difference between the two eras [3,8].

Risk factors — Most children with IE have an identifiable risk factor for the disease.

Congenital heart disease — Children with CHD, especially those with cyanotic heart disease, are at increased risk of developing IE. Underlying CHD is present in approximately 35 to 60 percent of pediatric IE cases [2,6,8-11]. The risk of IE is highest in patients with complex cyanotic CHD, especially in those who have had surgical intervention [4,9,12-17].

Reported incidence rates of IE in children with CHD range from 25 to 60 per 100,000 person-years, which is several orders of magnitude higher than in the general pediatric population [4,5,18]. In these reports, the CHD lesions at highest risk for IE included cyanotic lesions, endocardial cushion defect, left-sided lesions, and ventricular septal defects (VSDs). Other risk factors included cardiac surgery within six months and age <3 years.

There is a particularly high risk for IE in patients with tetralogy of Fallot who undergo transcatheter pulmonary valve replacement with bovine jugular vein prostheses [19]. This issue is discussed in greater detail separately. (See "Tetralogy of Fallot (TOF): Long-term complications and follow-up after repair", section on 'Endocarditis'.)

In a study of 3840 pediatric hospital admissions for IE from the Nationwide Inpatient Sample database (2000 to 2010), 54 percent had underlying cardiac conditions, of whom 81 percent had CHD [2]. The most common congenital heart defect was VSD (32 percent). Cyanotic lesions accounted for 25 percent of the CHD cases. A prosthetic valve was present in 7 percent, and other cardiac devices were present in 4 percent.

In a similar study of 1588 pediatric hospital admissions for IE from the Kid's Inpatient Database (2000 to 2003), the most common CHD diagnoses were tetralogy of Fallot (20 percent), ventricular septal defect (18 percent), hypoplastic left heart syndrome (10 percent), congenital aortic regurgitation (8 percent), D-transposition of the great arteries (6 percent), and patent ductus arteriosus (5 percent) [9].

Central venous catheters — An indwelling CVC is another major risk factor for pediatric IE [20]. At-risk pediatric populations for IE include critically ill and premature infants and children with cancer or connective tissue disorders. The increased use of CVCs in these pediatric groups appears to be a major factor for IE [9,12,13,20,21]. The risk is similarly increased with use of other intracardiac devices (eg, ventriculoatrial shunts, pacemakers, implantable cardioverter-defibrillators, and prosthetic and bioprosthetic valves). In a study of 3840 pediatric hospital admissions for IE (2000 to 2010), 7 percent of patients with underlying cardiac conditions had a prosthetic valve and 4 percent had another cardiac device [2]. As use of these devices becomes more common, the relative proportion of device-related IE increases. (See "Intravascular catheter-related infection: Epidemiology, pathogenesis, and microbiology" and "Hydrocephalus in children: Management and prognosis", section on 'CSF shunt'.)

Rheumatic heart disease — In developed countries, the incidence of rheumatic heart disease has declined dramatically since the 1960s, and in the modern era, rheumatic heart disease is an uncommon predisposing condition for IE in children [6,9]. In a study of 3840 pediatric hospital admissions for IE (2000 to 2010), 15 percent of patients with underlying cardiac conditions had rheumatic heart disease [2]. In resource-limited settings, rheumatic heart disease remains an important risk factor. (See "Acute rheumatic fever: Epidemiology and pathogenesis", section on 'Epidemiology' and "Clinical manifestations and diagnosis of rheumatic heart disease".)

Other risk factors — Injection drug use (associated with right-sided IE) and degenerative heart disease, which are important predisposing factors in the adult population, are less commonly seen in children [6,22].

PATHOGENESIS — 

IE is the result of a series of complex interactions among blood-borne pathogens, damaged endothelium, fibrin, and platelets [23].

●The endocardial surface is initially injured by shear forces associated with turbulent blood flow in children with congenital heart disease (CHD), or indwelling central venous catheters in children without CHD.

●At the site of endothelial damage, fibrin, platelets, and occasionally red blood cells are deposited and initially form a noninfected thrombus.

●Transient bacteremia (which occurs in normal children) or fungemia results in adherence of microbial pathogens to the injured endocardium and thrombus. Subsequent fibrin and platelet deposition over the infected vegetation result in a protective sheath that isolates the organisms from host defenses and permits rapid proliferation of the infectious agent.

Involvement of other organs is secondary to embolization or immune-mediated processes (eg, glomerulonephritis). (See 'Clinical manifestations' below and 'Complications' below.)

MICROBIOLOGY — 

Although a variety of microorganisms can cause IE, staphylococci and streptococci species are the most common pathogens associated with IE in children [2,9,24,25]. In a large retrospective study that included culture results on >2500 children hospitalized for IE, the relative frequency of different pathogens varied according to whether the child had underlying congenital heart disease (CHD) [2]:

●Among children with underlying CHD:

•Staphylococcus aureus – 28 percent

•Other Staphylococcus species – 7 percent

•Viridans streptococci – 33 percent

•Other streptococci – 17 percent

•Gram-negative bacilli – 5 percent

•Polymicrobial – 11 percent

●Among children without underlying heart disease:

•S. aureus – 47 percent

•Other Staphylococcus species – 6 percent

•Viridans streptococci – 18 percent

•Other streptococci – 10 percent

•Gram-negative bacilli – 8 percent

•Polymicrobial – 12 percent

These results demonstrate the relatively high incidence of endocarditis due to S. aureus, particularly among children without heart disease. IE caused by S. aureus is typically an acute fulminant process with a high mortality rate, as compared with IE due to most other pathogens. (See 'Clinical manifestations' below and 'Outcome' below.)

Although patients with indwelling catheters are at risk for bacteremia with gram-negative organisms, gram-negative bacterial endocarditis is rare. This is probably due to the poor ability of gram-negative bacteria to adhere to the endocardium.

In neonates with IE, likely etiologic agents include S. aureus, coagulase-negative staphylococci, Klebsiella pneumonia, and Enterobacter species, among others [26].

Similar to adults, blood cultures remain negative in 5 to 7 percent of children with IE [6,22,23,27]. Potential reasons for this include previous administration of antimicrobial agents, inadequate microbiologic techniques, or infection with highly fastidious bacteria or nonbacterial pathogen. Consultation with an infectious disease expert is recommended in all cases of culture-negative endocarditis. (See "Blood culture-negative endocarditis: Epidemiology, microbiology, and diagnosis".)

Fungal endocarditis is rare and is typically caused by Candida species [6]. Indwelling catheters and high glucose concentrations in parenteral nutrition have contributed to the occurrence of fungal endocarditis, especially in preterm infants [28]. Fungal endocarditis is frequently associated with large, friable vegetations that can embolize, producing complications in other organ systems. (See 'Complications' below and "Candida infections in neonates: Epidemiology, clinical manifestations, and diagnosis", section on 'Endocarditis'.)

CLINICAL MANIFESTATIONS

Acuity of presentation — IE can present acutely, or it may have a subacute presentation.

●Acute IE — Acute IE is a rapidly progressive and fulminant disease. These patients typically have high fevers and appear severely ill. An acute presentation is commonly seen in patients with IE due to S. aureus or streptococcus pneumoniae, which can cause rapid destruction of heart valve tissue, abscess formation, embolic phenomena, and hemodynamic instability [29].

●Subacute IE — The subacute presentation is more common. It is characterized by a prolonged course of low-grade fever and nonspecific complaints including fatigue, arthralgias, myalgias, chills, night sweats, weight loss, and exercise intolerance. The presence of a cluster of these symptoms in a patient at risk for IE (ie, those with underlying congenital heart disease [CHD] or indwelling central venous catheter) should raise the possibility of IE as a potential diagnosis. In addition, there is a risk of immunologic sequelae, such as immune-mediated glomerulonephritis. The less virulent pathogens, such as viridans group streptococci and coagulase-negative staphylococci, typically have a subacute presentation.

Clinical findings — The clinical findings of IE vary by age, underlying comorbidities, pathogen, and severity of infection. The clinical presentation of pediatric IE is variable and depends upon the extent of the local cardiac disease, degree of involvement of other organs (eg, embolization), and the pathogen.

●Neonates – In the neonate, the presentation of IE may be indistinguishable from bacterial sepsis. (See "Neonatal bacterial sepsis: Clinical features and diagnosis in neonates born at less than 35 weeks gestation", section on 'Clinical manifestations'.)

The signs of IE in the newborn are variable and nonspecific [30,31]. Common manifestations include feeding intolerance, tachycardia, respiratory distress, hypotension, and a new or changing murmur. Fever may be absent.

Neonates with right-sided IE in association with central venous catheters characteristically have little clinical evidence of disease other than persistently positive blood cultures in the setting of appropriate antibiotic treatment [26].

Fungal IE can present as an acute fulminant infection [13]. (See "Candida infections in neonates: Epidemiology, clinical manifestations, and diagnosis", section on 'Endocarditis'.)

●Older infants and children – In older infants and children, the clinical findings of IE correspond to the underlying pathologic phenomena of bacteremia/fungemia, endothelial damage, immune response, and embolization [23].

•Signs of bloodstream infection – Signs associated with bloodstream infection include fever, vasodilation, and tachycardia. Other common symptoms of subacute IE include malaise, headache, myalgias, and arthralgias. (See "Pathophysiology of sepsis", section on 'Circulation'.)

•Signs of valvulitis and damaged endocardium – These may include:

-A new or changing murmur.

-Signs of acute heart failure (eg, dyspnea, tachypnea, rales) or poor systemic perfusion due to perforation of a valve, chordal rupture, or poor ventricular function.

-Worsening cyanosis in children with underlying cyanotic CHD if IE involves either a systemic-pulmonary shunt or conduit. This is because the infection may obstruct blood flow across the shunt or conduit.

•Immune-mediated complications – Glomerulonephritis may develop in children who present with subacute IE as a consequence of immune-mediated disease. (See 'Complications' below.)

•Embolic complications – In children with IE, septic emboli are common, resulting in extracardiac infection (eg, osteomyelitis, pneumonia, lung abscess) or infarction to major vessels and organs. Emboli to the brain may result in neurologic symptoms (eg, seizures, headache, strokes, or altered mental status). Other major organs that may be at risk for embolic episodes include the kidneys, lungs, gastrointestinal tract, limbs, and eyes. (See 'Complications' below.)

•Relatively uncommon manifestations highly suggestive of IE – Janeway lesions (picture 1), Osler nodes (picture 2), and Roth spots are uncommon manifestations of IE in children. Nevertheless, these findings are highly suggestive of IE. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Clinical manifestations'.)

Laboratory findings — Nonspecific laboratory findings that support the diagnosis of IE include:

●Anemia (either hemolytic or anemia of chronic disease), which is a common feature of IE

●Elevated inflammatory markers (eg, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP], procalcitonin)

●Urinalysis showing hematuria, proteinuria, and red blood cell casts is suggestive of glomerulonephritis, a minor diagnostic criterion

ECG and chest radiograph findings

●Electrocardiography (ECG) – ECG is generally not helpful in the diagnosis of IE with the exception of IE with periannular extension, in which prolongation of the PR interval or frank heart block can occur.

●Chest radiography – The chest radiograph is often normal. Nonspecific findings may include cardiomegaly, pulmonary edema, and focal pulmonary infiltrates in patients with pulmonary septic emboli.

DIAGNOSIS — 

The diagnosis of IE is based upon history, physical examination, blood cultures, laboratory tests, and echocardiography.

Blood cultures — Blood cultures are the cornerstone of microbiological diagnosis of IE. A minimum of three blood cultures should be obtained over a time period of a few hours to two days depending upon the severity of the illness. In most patients, three blood cultures are obtained from separate venipunctures in the first 24 hours and an additional two blood cultures in the next 24 hours if there is no growth from the initial cultures [29].

In critically ill children, three separate venipunctures for blood cultures should be performed as quickly as possible (ideally within <30 minutes) and empiric antibiotic therapy started promptly. In children who are not severely ill, antibiotic therapy can be withheld for at least 48 hours while the blood cultures are collected [29]. (See 'Empiric therapy' below.)

Unless there has been prior antibiotic therapy, it is generally not necessary to obtain more than five blood cultures over two days. In addition, it is not necessary to obtain blood cultures at the time of fever since bacteremia in IE is usually continuous.

It is important to obtain adequate volumes of blood for each blood culture bottle (1 to 3 mL in infants and young children and 5 to 7 mL in older children). If there is a limited volume of blood, preferential culturing of the aerobic culture bottle is suggested because almost all cases of bacterial IE are due to aerobic organisms, and culturing for anaerobes is rarely useful.

Cardiac imaging

Echocardiography — An echocardiogram should be performed in all patients with suspected IE. (See "Role of echocardiography in infective endocarditis".).

●Indications – Indications for echocardiography include:

•Clinical suspicion for IE based upon a combination of concerning clinical findings, especially in a patient with underlying risk factors (eg, congenital heart disease [CHD], prosthetic material, central venous catheter). (See 'Clinical manifestations' above.)

•Persistent bacteremia.

•Isolation of an organism that is highly associated with IE (eg, viridans group streptococci) in the bloodstream. (See 'Microbiology' above.)

●Aims of echocardiography – In patients with IE, echocardiography aims to (see "Role of echocardiography in infective endocarditis"):

•Identify the size and location of a vegetation (movie 1)

•Characterize the extent of valve damage and the degree of valvar stenosis or regurgitation (movie 2)

•Assess for perivalvar extension of infection or abscess

•Assess ventricular function

•In patients with shunts or conduits, assess for obstruction of the conduit or shunt

•In patients with a prosthetic valves, assesses for evidence of partial dehiscence

In addition, echocardiography can be used to serially monitor hemodynamic and valvular function, and the resolution of vegetations in response to medical treatment. (See 'Monitoring' below.)

●TTE versus TEE – In most pediatric cases of suspected IE, transthoracic echocardiography (TTE) is adequate to detect the presence of a vegetation and assess hemodynamic and valve function. This is especially true in infants and younger children (<10 years and <60 kg). TTE is a much more sensitive diagnostic tool in children compared with adults [23,32,33].

However, in some children, TTE provides inadequate imaging due to suboptimal echocardiographic windows, and transesophageal echocardiography (TEE) may be necessary. Inadequate TTE imaging is most likely to occur in the following patients [23]:

•Overweight children.

•Muscular children.

•Children with significant respiratory disease.

•Children with surgically repaired complex CHD, as artifacts from prosthetic material (grafts and conduits) and valves may interfere with TTE imaging [34]. Suboptimal echocardiographic windows are frequently present in the immediate postoperative period.

•Children with chest wall disruption from prior surgery or trauma.

•Children with congenital anomalies involving the thoracic cage (eg, severe pectus excavatum).

In addition, in children with aortic valve IE, TEE is superior to TTE for the detection of aortic root abscess. Thus, TEE may be warranted if there are findings on TTE consistent with periannular extension (eg, changing aortic root dimensions) or if there are concerning findings on electrocardiogram (eg, prolonged PR interval or heart block) [29,35,36].

●Sensitivity and specificity – TTE has a reasonably high sensitivity for detecting IE (approximately 70 to 90 percent) with a specificity that approaches 100 percent [37]. However, both TTE and TEE may give false-negative results if the vegetations are small or if embolization of the vegetation has occurred. The absence of visible vegetations on echocardiogram does not exclude IE.

Other imaging modalities — Other imaging modalities such as cardiac computed tomography (CT), fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET)/CT, and cardiac magnetic resonance (CMR) imaging may be useful in select clinical situations, including when suspicion for endocarditis is high but TTE or TEE are nondiagnostic. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on 'Cardiac imaging'.)

FDG-PET/CT targets inflammatory cells and has been particularly successful in identifying infection of cardiac devices including prosthetic valves, implanted electronic devices, and ventricular assist devices. In addition, FDG-PET/CT can identify distant emboli and early spread of infection prior to anatomic changes. However, because of perioperative inflammatory changes, this modality is generally not helpful in identifying IE within three months of surgery (ie, it has a high false-positive rate in this setting). FDG PET/CT is discussed in greater detail separately. (See "Prosthetic valve endocarditis: Epidemiology, clinical manifestations, and diagnosis", section on 'Emerging imaging modalities'.)

Diagnostic criteria — The accepted criteria for diagnosis of pediatric IE are the Duke-International Society for Cardiovascular Infectious Disease (ISCVID) criteria, which categorize patients as "definite IE," "possible IE," and "rejected IE" based on pathologic and clinical criteria [38]. These criteria are summarized in the tables (table 1 and table 2) and discussed in detail separately. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on '2023 Duke-ISCVID criteria'.)

TREATMENT — 

In general, the principles of treatment of IE in children are the same as in adults. Patients with IE-associated valve dysfunction causing symptomatic heart failure and patients with persistent fevers and bacteremia despite appropriate antibiotic therapy may be candidates for surgical intervention.

Antibiotic therapy — In general, antibiotic therapy for IE should be targeted to the organism isolated from blood cultures. In most cases of pediatric IE, antibiotic therapy can be deferred until blood culture results are available. This is particularly important since an accurate microbiologic diagnosis is a critical first step in determining the treatment approach.

Empiric therapy — The decision to start empiric therapy pending culture results depends on the clinical stability of the patient.

●Patients with hemodynamic instability or other severe manifestations – For patients with severe manifestations of acute IE, blood cultures should be obtained as quickly as possible so that empiric antibiotic therapy can be started promptly.

The appropriate empiric regimen varies depending on the nature of the involved valve (eg, native versus prosthetic valve); this is discussed separately. (See "Antimicrobial therapy of left-sided native valve endocarditis", section on 'Empiric therapy' and "Antimicrobial therapy of prosthetic valve endocarditis", section on 'Empiric therapy'.)

●Patients who are clinically stable – In children who are clinically stable, antibiotic therapy can be withheld for at least 48 hours until the results of blood cultures are available [29]. Antibiotic therapy is then directed at the specific pathogen, as discussed in the next section.

Pathogen-specific therapy — Antibiotic choice, dose, and duration of treatment depend upon the pathogen. Consultation with infectious disease specialist is advised.  

Antibiotic regimens for common bacterial pathogens in pediatric IE are summarized in the tables and discussed in greater detail separately (see "Antimicrobial therapy of left-sided native valve endocarditis" and "Antimicrobial therapy of prosthetic valve endocarditis"):

●Viridans group streptococci and Streptococcus gallolyticus (bovis) (table 3A-D)

●Enterococci (table 4)

●Staphylococci (table 5A-B)

●Gram-negative organisms (including Haemophilus sp, Aggregatibacter sp, Cardiobacterium hominis, Eikenella corrodens, and Kingella sp [ie, the HACEK group]) (table 6)

Culture-negative endocarditis — Culture-negative endocarditis (CNE) occurs rarely in children and may be diagnosed when a patient has clinical or echocardiographic evidence of IE but persistently negative blood cultures [29]. Patients with suspected CNE should be managed in consultation with a pediatric infectious disease specialist. Important considerations in determining the treatment regimen include prior antibiotic exposure, route of acquisition of the infection, whether the infection is community acquired or nosocomial, whether the valve infected is native or prosthetic, and whether the infection is acute or subacute [29].

Surgical intervention — Determination of the need for surgical intervention should be individualized using a multispecialty approach, including involvement of experts in infectious disease, cardiology, and cardiothoracic surgery. Considerations in children are generally similar to those in adults with IE. The most common reasons for surgical intervention include heart failure, progressive valve dysfunction, and embolic phenomena [29,39,40]. Limited pediatric data are available, and clinical practice is largely guided by adult guidelines.

Recommendations for surgical intervention in patients with IE are reviewed in detail elsewhere. (See "Surgery for left-sided native valve infective endocarditis".)

MONITORING — 

The following tests are helpful in monitoring the patient's clinical course during treatment and after completion of antibiotic therapy:

●Antimicrobial levels – Patients receiving treatment with gentamicin or vancomycin should have blood levels for these drugs checked at least once a week. The dose of gentamicin should be adjusted for a target peak level of 3 to 4 mcg/mL and a trough level of <1 mcg/mL, although higher levels may be required for some gram-negative infections [29]. For vancomycin, the target trough level is 10 to 15 mcg/mL, though higher levels (ie, 15 to 20 mcg/mL) may be required initially for methicillin-resistant staphylococci. Children with kidney function impairment require dose adjustments for these agents [29].

●Echocardiography – Repeat echocardiogram may be warranted during treatment of IE to assess for changes in vegetations and evaluate valve and myocardial function. This is particularly true of patients exhibiting clinical deterioration, new murmurs, persistent fevers, or bacteremia. Once treatment is completed, repeat evaluation may be necessary to establish a new baseline of valvar and myocardial function for the patient [41].

●Repeat blood cultures – Repeat blood cultures are always warranted if there is recurrence of symptoms. Cultures performed after completion of antibiotic therapy may be helpful to demonstrate adequacy of treatment in certain cases (eg, in a patient with S. aureus prosthetic valve infection associated with prolonged bacteremia); however, repeat blood cultures may also result in isolation of a contaminant [29].

PREVENTION — 

Strategies to prevent IE in children include oral hygiene for prevention of oral disease and antimicrobial prophylaxis for high-risk patients when undergoing invasive procedures [29]. We provide antibiotic prophylaxis in children who are at highest risk for IE based upon guidance from the American Heart Association [42]. Antibiotic IE prophylactic regimens for children are summarized in the table (table 7). Antibiotic prophylaxis for IE is discussed in detail separately, including discussion of patient selection and relevant procedures. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

OUTCOME

Mortality — Reported mortality rates among children with IE range from 1 to 8 percent [2,8,9,11,18]. Mortality is highest among patients with underlying cyanotic congenital heart disease (CHD) and with infection caused by S. aureus [2,9]. In addition, the risk of mortality is increased in patients who develop complications from IE, particularly heart failure, perivalvular abscess, stroke, or septic emboli with distant abscesses.

Complications — Complications seen in children with IE are generally similar to those seen in adults; however, as a general rule, these complications occur less commonly in children compared with adults.

Factors that predispose to the development of complications in children with IE include [23].

●Prosthetic cardiac valves

●Left-sided involvement

●S. aureus or fungal IE

●Previous IE

●Prolonged symptoms (≥3 months)

●Cyanotic congenital heart disease

●Systemic-to-pulmonary shunts

●Poor clinical response to antimicrobial therapy

Complications of IE include cardiac sequelae and end-organ infection or infarction due to embolic events:

●Cardiac complications – Cardiac complications include the following (see "Complications and outcome of infective endocarditis", section on 'Cardiac complications'):

•Heart failure – Heart failure can be caused by perforation of the valve, rupture of an infected chordae, or perivalvar leaks or dehiscence in patients with prosthetic valve. Poor ventricular function often accompanies worsening valvar regurgitation. Heart failure is the most common indication for surgical intervention in patients with IE. (See "Surgery for left-sided native valve infective endocarditis".)

•Perivalvular abscess – Extension of infection beyond the endothelium may result in a fistula tract or perivalvular infection (eg, abscess), which may cause an arrhythmia or atrioventricular heart block. Transesophageal echocardiography (TEE) is more sensitive for detection of myocardial abscess than transthoracic echocardiography (TTE). (See "Role of echocardiography in infective endocarditis", section on 'Perivalvular abscess or fistula'.)

•Extension of infection into a prosthetic shunt or conduits may occlude the graft. These infections require surgical intervention because they rarely respond to medical management.

●Metastatic infection – Infection at other sites can occur from septic emboli resulting in osteomyelitis, pneumonia, or distal abscesses in the kidneys, spleen, brain, or soft tissues.

●Mycotic aneurysms – Can occur in any systemic artery and result from septic embolization or, occasionally, from contiguous spread of infection. This complication is usually an indication for surgery.

●Stroke – Stoke occurs in 5 to 15 percent of pediatric IE cases, chiefly in the setting of left-sided IE [2,11,43].

●Acute kidney injury (AKI) – AKI can be caused by renal infarction, glomerulonephritis (as a result of an immune-mediated secondary process), and drug-induced acute interstitial nephritis. AKI occurs in approximately 10 percent of pediatric patients with IE [2].

●Other embolic events, including:

•Pulmonary embolism (typically occurs in the setting of right-sided IE)

•Ischemia of the extremities

•Splenic infarction

•Visual impairment (due to embolism or due to endophthalmitis as a result of bacteremic seeding)

•Acute myocardial infarction

The complications of IE are discussed in greater detail separately. (See "Complications and outcome of infective endocarditis".)

SOCIETY GUIDELINE LINKS — 

Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment and prevention of infective endocarditis".)

SUMMARY AND RECOMMENDATIONS

●Incidence – Infective endocarditis (IE) is uncommon in children, with an estimated annual incidence of <5 cases per 100,000 per year. Most children with IE have identifiable risk factors, most commonly underlying congenital heart disease (CHD) and/or an indwelling central venous catheter (CVC). (See 'Incidence' above and 'Risk factors' above.)

●Microbiology – Streptococci (viridans group and other streptococci) and staphylococci species (S. aureus and coagulase-negative staphylococci) are the most common pathogens associated with IE in children. Other less common pathogens are listed above. (See 'Microbiology' above.)

●Clinical presentation – IE can have an acute or subacute presentation. (See 'Acuity of presentation' above.)

•Acute IE is a rapidly progressive fulminant disease with high, spiking fevers and an increased likelihood of complications, including hemodynamic instability and heart failure. Staphylococcus aureus is the organism most commonly associated with acute IE and carries a higher mortality risk.

•The subacute presentation is more common. It is characterized by a prolonged course of low-grade fevers and nonspecific complaints, including fatigue, chills, night sweats, arthralgias, myalgias, weight loss, and exercise intolerance.

●Clinical findings – Clinical findings consistent with a diagnosis of IE include fevers, a new or changing heart murmur, signs of heart failure (dyspnea, tachypnea, rales), and evidence of embolic complications (eg, stroke, brain abscess, osteomyelitis, pneumonia). (See 'Clinical findings' above.)

●Laboratory findings – Nonspecific laboratory findings that support the diagnosis of IE include (see 'Laboratory findings' above):

•Anemia

•Elevated inflammatory markers (eg, erythrocyte sedimentation rate, C-reactive protein, procalcitonin)

•Hematuria, proteinuria, and/or red blood cell casts on urinalysis

●Diagnosis – The clinical diagnosis of IE is made by fulfilling the 2023 Duke-International Society for Cardiovascular Infectious Disease (ISCVID) criteria (table 1 and table 2). blood cultures, echocardiogram findings, and other clinical findings. (See "Clinical manifestations and evaluation of adults with suspected left-sided native valve endocarditis", section on '2023 Duke-ISCVID criteria'.)

The diagnostic criteria are based upon (see 'Diagnosis' above):

•Blood cultures (a minimum of three blood cultures should be obtained) (see 'Blood cultures' above)

•Echocardiogram findings (see 'Echocardiography' above)

•Other clinical findings (see 'Clinical findings' above)

●Treatment – The principles of treatment of IE in children are the same as those for adults (see 'Treatment' above):

•Antibiotic therapy – The choice, dose, and duration of antibiotic therapy depend upon the pathogen (see 'Pathogen-specific therapy' above):

-Viridans group streptococci and Streptococcus gallolyticus (bovis) (table 3A-D)

-Enterococci (consultation with an infectious disease specialist is recommended (table 4))

-Staphylococci (table 5A-B)

-Gram-negative organisms (including Haemophilus sp, Aggregatibacter sp, Cardiobacterium hominis, Eikenella corrodens, and Kingella sp [ie, the HACEK group]) (table 6)

•Surgical intervention – Determination of the need for surgical intervention should be individualized using a multispecialty approach, including involvement of experts in infectious disease, cardiology, and cardiothoracic surgery. Considerations in children are generally similar to those in adults with IE. (See "Surgery for left-sided native valve infective endocarditis".)

●Prevention – Prophylactic antibiotic therapy for IE (table 7) is reserved for patients with the highest risk of IE, as discussed separately. (See "Prevention of endocarditis: Antibiotic prophylaxis and other measures".)

●Outcome – The mortality rate for pediatric IE is approximately 1 to 8 percent. Prematurity, cyanotic CHD, and IE due to S. aureus are important risk factors for mortality. (See 'Mortality' above.)

Complications of IE include cardiac sequelae (eg, heart failure, perivalvular abscess) and end-organ infection or infarction due to embolic events. (See 'Complications' above and "Complications and outcome of infective endocarditis".)