Infective endocarditis

• Infective endocarditis (IE) is an infection, usually bacterial, of the inner lining of the heart, most often one of the heart valves, native or artificial.
• It is uncommon but dangerous: in-hospital mortality is often quoted at about 15 to 25% even in well-resourced systems.^[1]
• Fever is present in up to about 90% of patients, and a new or changing heart murmur in about 85%.^[1]
• The likely organisms depend on how and where the infection is acquired: viridans streptococci in community-acquired native valve disease, Staphylococcus aureus after healthcare exposure or in people who inject drugs, enterococci in older patients, HACEK organisms and fungi in selected groups.
• Diagnosis rests on repeated blood cultures before antibiotics and echocardiography, judged by the Duke criteria; treatment is several weeks of intravenous antibiotics, with surgery for heart failure, uncontrolled infection, or large vegetations at risk of embolism.

By the end of this page you should be able to:

1. List the cardiac and non-cardiac risk factors for IE and say why they matter.
2. Match the likely organism to the clinical setting.
3. Recognise the major and minor features of IE, including the peripheral signs.
4. Apply the modified Duke criteria and plan the first-line investigations.
5. Outline the usual antibiotic regimens and durations, and state when surgery is indicated.
6. Describe prevention of IE, including who needs dental prophylaxis and with what.
7. Compare the 2015 AHA and 2023 ESC approaches where they differ.

Infective endocarditis is infection and inflammation of the endocardium, the thin lining inside the heart chambers and, most importantly, the heart valves. It occurs when organisms in the bloodstream settle on damaged or artificial valve tissue, or on other intracardiac material, and grow into vegetations: soft masses of organisms, platelets and fibrin that sit on the valve and can destroy the leaflet underneath.

IE is not a single disease. Native valve endocarditis (NVE) is infection of a person's own valve. Prosthetic valve endocarditis (PVE) is infection of an artificial valve, or material used at valve repair. Right-sided IE, usually of the tricuspid valve, is a separate clinical entity, often linked to intravenous drug use and to catheter-related infection. Device-related endocarditis involves pacemaker or defibrillator leads and the valves at which they sit.

Global incidence is estimated at 3 to 7 cases per 100,000 person-years.^[1] In-hospital mortality is about 15 to 25% in recent data, and mortality has not fallen much despite better surgery and antibiotics.^[1] The disease now affects older patients: the median age of affected patients is nearing 73 years.^[1] Rheumatic heart disease, once the commonest predisposing valve disease in younger people and in low-resource countries, has fallen in high-income countries and been replaced by degenerative valve disease, congenital heart disease, and healthcare exposure.^[1]

IE consumes a large burden of illness: it accounted for over 1.7 million disability-adjusted life years globally in 2019.^[1] Healthcare-associated IE has become more common and carries worse outcomes than community-acquired disease.^[1]

• Prosthetic valves. PVE accounts for over 20% of all IE cases in large international cohorts.^[1] After prosthetic valve replacement, whether surgical or transcatheter, incidence is about 3 to 10 cases per 1,000 person-years.^[1]
• Prior IE. Recurrence is reported at about 5%.^[1]
• Congenital heart disease (CHD). Unrepaired or complex cyanotic lesions carry a lifetime IE risk of roughly 2 to 8.5%, highest in unrepaired or complex cyanotic CHD.^[1] Bicuspid aortic valve, present in less than 2% of the general population, is over-represented in IE, with a recent meta-analysis showing a 12-fold increase in IE in people with bicuspid aortic valve.^[1] Mitral valve prolapse, especially with regurgitation, is a well-established risk factor; one United States study estimated about 87 cases per 100,000 person-years in people with mitral valve prolapse.^[1]
• Rheumatic and degenerative valve disease. Rheumatic heart disease remains an important predisposing factor in endemic regions and in migrants from them; degenerative valve disease is now common in older patients.^[1]
• Cardiac implantable electronic devices (CIEDs), such as pacemakers and defibrillators, can become infected through lead infections and bacteremia.^[1]

• Injecting drug use. IE rates among people who inject drugs are reported as about 100 times those in non-users in North American studies.^[1] Right-sided, Staphylococcus aureus IE is typical.
• Intravascular and dialysis access. Central venous catheters, hemodialysis with arteriovenous grafts, and indwelling catheters are key contributors to healthcare-associated IE; hemodialysis patients have an IE risk 50 to 70 times that of the general population.^[1]
• Advanced age (over 60 years) carries about a fivefold increased risk compared with the general population.^[1]
• Immunocompromise from HIV, malignancy, chronic corticosteroids, or uncontrolled diabetes increases both incidence and mortality.^[1]
• Chronic liver disease, including cirrhosis, is also associated with higher IE risk.^[1]

IE begins with bacteremia. Organisms adhere to damaged or prosthetic valve endothelium, often where flow is turbulent. A vegetation then forms as organisms are coated with platelets and fibrin, which protects them from host defences and from many antibiotics.

From there, IE does three kinds of damage:

• Local valve destruction produces regurgitation, sometimes rapidly, and can progress to abscess, fistula or dehiscence of a prosthesis.
• Emboli break off from vegetations and travel with the blood: to brain, spleen, kidneys, limbs and gut from the left side; to lungs from the right side.
• Immune complex disease. Prolonged infection drives deposition of immune complexes, producing glomerulonephritis, arthralgia and other systemic features.

The risk of embolisation is much higher when vegetations exceed 10 mm in length, and is further predicted by vegetation mobility, prior embolic events, mitral valve involvement, and infection with Staphylococcus aureus.^[1]

Fever is the most common symptom, present in up to about 90% of cases, followed by chills (40 to 75%), malaise (50 to 70%), fatigue (25 to 80%), anorexia (25 to 50%), weight loss (25 to 35%) and night sweats (25 to 35%).^[1] A new or changing cardiac murmur is present in about 85% of patients.^[1]

Figure 1Splinter hemorrhage

Enlarge

Long description

Clinical photograph of a splinter haemorrhage under a fingernail (thin reddish-brown longitudinal line beneath the nail plate of the little finger).

Figure 2Janeway lesion

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Long description

A clinical photograph of a Janeway lesion, a painless erythematous macule on the palm of a 36-year-old man with staphylococcal infective endocarditis.

• Janeway lesions: non-tender erythematous macules on the palms and soles, from septic micro-emboli.
• Osler nodes: tender nodules on the fingers or toes, from immune complex vasculitis.
• Splinter haemorrhages: thin vertical lines under the nails.
• Roth spots: retinal haemorrhages with pale centres, from immune complex deposition; cotton-wool spots can look similar.
• Septic emboli: strokes, splenic or renal infarcts, limb ischaemia, mesenteric ischaemia, lung abscesses from right-sided disease. Neurological complications occur in about 21% of patients, and brain abscess in 1 to 7%.^[1]
• Glomerulonephritis from immune complexes produces haematuria, proteinuria and rising creatinine.

These classic peripheral signs are less common than they once were, because patients now present earlier; they are still important clues, particularly in subacute disease.^[1]

Heart failure from valvular damage occurs in about 25 to 30% of patients and may present as dyspnoea and oedema rather than fever.^[1] Embolic stroke can be the first sign. In one series heart failure occurred in about 28.5% of patients with left-sided IE.^[1] Septic pulmonary emboli are more common in right-sided IE, usually in people who inject drugs.^[1]

Fever plus murmur is not IE. The main alternatives to consider are:

• acute rheumatic fever
• non-infective thrombotic endocarditis (marantic endocarditis, linked to antiphospholipid syndrome, lupus or malignancy; sterile blood cultures)
• atrial myxoma or other cardiac mass
• vasculitis and connective tissue disease
• pyrexia of unknown origin from another source
• a simple bacteraemia with a functional flow murmur.

The clinical setting, repeated blood cultures, inflammatory markers and, above all, echocardiography separate these.

Take at least three sets of blood cultures from separate sites before starting antibiotics: in acute illness (for example, sepsis or fever with a new murmur) take all three over one to two hours; in subacute illness they may be spaced over several hours, and antibiotics can be withheld while results are awaited.^[1] In the 2023 Duke-ISCVID criteria, organisms that commonly cause IE isolated from two or more separate blood culture sets, or organisms that rarely cause IE isolated from three or more sets, count as a major microbiologic criterion.^[1]

Automated systems grow most pathogens within 5 days; slow-growing organisms need longer incubation.^[1] Between 2.5 and 31% of cases are culture-negative, often because of prior antibiotics or infection with fastidious or intracellular organisms such as Coxiella burnetii, Bartonella species or Tropheryma whipplei.^[1]

In culture-negative IE, serology for C. burnetii and Bartonella, plus polymerase chain reaction (PCR) and 16S ribosomal RNA gene sequencing of resected valve tissue or embolic material, greatly increase diagnostic yield.^[1] Newer methods (matrix-assisted laser desorption ionisation time-of-flight mass spectrometry, metagenomic sequencing) are promising but are limited by cost and availability.^[1]

Transthoracic echocardiography (TTE, ultrasound through the chest wall) is the first test. It identifies vegetations, abscesses, location, size, shape and mobility, and tracks response to treatment.^[1] Transoesophageal echocardiography (TEE, a probe in the oesophagus) is recommended when TTE is equivocal but suspicion remains high, when complications are suspected, or with prosthetic valves and intracardiac devices.^[1] Its advantage is largest for small vegetations and prosthetic valves: sensitivity for vegetations in prosthetic valve endocarditis rises from about 50% with TTE to about 92% with TEE; in native valve endocarditis from about 70% to about 96%.^[1] TEE detects abscesses with about 90% sensitivity against about 50% for TTE.^[1]

Three-dimensional TEE improves morphological characterisation, valve perforation, dehiscence and intracardiac fistulae, and may change surgical plans, but its lower temporal resolution can overestimate vegetation size.^[1]

• Cardiac computed tomography (CT) identifies perivalvular complications (abscess, fistula, pseudoaneurysm) with sensitivity about 81% against about 63% for echocardiography, helps when prosthetic material shadows the valve, and assists operative planning; it is less sensitive for small vegetations and leaflet perforation.^[1]
• Cardiac magnetic resonance (CMR) helps when echo is inconclusive and can show embolic lesions and delayed enhancement from inflammation, but is limited by prosthetic artefact.^[1]
• 18F-fluorodeoxyglucose positron emission tomography with CT (PET/CT) is recommended (ESC 2023, Class I) when prosthetic valve infection is suspected and echo is inconclusive; its sensitivity in prosthetic valve endocarditis is about 85.5% with specificity about 86%.^[1] It also searches the whole body for the portal of entry and distal infection.

The modified Duke criteria (2000 revision) classify IE as definite, possible or rejected using major and minor criteria.^[2] The standard list is summarised below.

The 2023 Duke-ISCVID update broadens imaging (PET/CT and cardiac CT for prosthetic valve and device infection), adds valve PCR/16S sequencing, expands the list of typical organisms, and recognises intraoperative findings as a major criterion when other criteria are lacking.^[1] It improved sensitivity from 74.9% to 84.2% against the modified 2000 Duke criteria, with specificity 93.9% against 94.9%.^[1]

The organism table below is an approximate teaching summary; percentages vary by population and study.

Start high-dose intravenous empirical therapy as soon as blood cultures have been taken, guided by the clinical picture and local resistance.^[2][3] A practical approach:

• Suspected native valve IE in a stable patient: vancomycin plus a third- or fourth-generation cephalosporin (ceftriaxone or cefepime), covering Staphylococcus aureus, viridans streptococci and enterococci.^[1]
• Prosthetic or healthcare-associated IE: broader cover, typically vancomycin plus cefepime, with agents chosen according to the timing of valve implantation and local resistance.^[1]
• People who inject drugs: ensure cover for Staphylococcus aureus, including methicillin-resistant strains, and consider cover for Pseudomonas species when Gram-negative organisms are suspected.^[1]

The AHA/IDSA 2015 statement favours vancomycin plus a third-generation cephalosporin for empiric native valve IE, particularly where MRSA or enterococci are possible.^[1][2] The 2023 ESC guidelines recommend a streamlined vancomycin-based empiric regimen without routine gentamicin, to limit kidney injury.^[1][3]

Once the organism and its susceptibilities are known, narrow therapy and treat for the full course. Typical adult regimens (interpret within local guidance) are:^[1]

• Viridans group streptococci: penicillin G or ceftriaxone, 4 weeks for native valve disease; 6 weeks for prosthetic valve disease. A 2-week course with gentamicin is an option for uncomplicated native valve disease with gentamicin-susceptible strains.
• Staphylococcus aureus, methicillin-susceptible: nafcillin or oxacillin (cefazolin is preferred with penicillin allergy or renal impairment), 6 weeks; cefazolin may be preferred in older or frail patients because of lower kidney toxicity.
• Staphylococcus aureus, methicillin-resistant: vancomycin (daptomycin if vancomycin-intolerant), for at least 6 weeks.
• Enterococcus faecalis: ampicillin plus ceftriaxone for 6 weeks (better renal safety than gentamicin combinations).
• HACEK organisms: ceftriaxone, 4 weeks native and 6 weeks prosthetic.
• Culture-negative IE: vancomycin plus cefepime for acute presentations, or vancomycin plus ampicillin-sulbactam for subacute presentations, for at least 4 to 6 weeks. ^[1]
• Fungal IE: liposomal amphotericin B with flucytosine, or a high-dose echinocandin, for at least 6 weeks, often with long-term oral suppression, plus surgery in most cases.

Native valve IE usually requires 4 weeks (streptococci) to 6 weeks (staphylococci, enterococci); prosthetic valve IE requires at least 6 weeks.^[1][2][3] Rifampin for prosthetic staphylococcal IE is usually started only after blood cultures have cleared, to avoid resistance.^[1]

The ESC 2023 guidelines also allow oral step-down therapy, and outpatient parenteral antibiotic therapy (OPAT), in selected stable patients with a confirmed pathogen and documented susceptibility, supported by the POET trial.^[1][3] The POET trial showed that switching to oral therapy after initial stabilisation was non-inferior to continuing intravenous therapy. It enrolled a highly selected group, mostly with streptococcal infection and few higher-risk patients, so the result should not be generalised to every patient.^[1][3]

Close clinical monitoring after treatment is advisable, with follow-up transthoracic or transoesophageal echocardiography, particularly after prosthetic valve or enterococcal infection, or when surgery was not performed.^[1]

About 25 to 50% of patients need valve surgery during the first admission.^[1] The main indications are:^[1][2][3]

1. Heart failure from severe valvular dysfunction (the most frequent indication, and the one with the greatest mortality benefit when surgery is timely).
2. Uncontrolled infection: perivalvular abscess, persistent bacteremia despite appropriate antibiotics, fistula, prosthetic dehiscence, or relapsing infection.
3. Large vegetations at risk of embolism, particularly vegetations larger than 10 mm with prior embolism or signs of heart failure; very large right-sided vegetations (about 20 mm) with recurrent pulmonary emboli or severe tricuspid regurgitation.
4. Structural complications, such as valve perforation or paravalvular abscess.

Timing matters. Evidence supports early surgery, sometimes within the first week, for patients with large vegetations (exceeding about 10 to 15 mm) plus prior embolism or early heart failure; the EASE trial found that early surgery reduced the composite of embolism or death at 6 months compared with conventional therapy.^[1] Surgery after a large stroke or intracranial haemorrhage may need delay to reduce neurological risk.^[1]

Both guidelines emphasise early surgical consultation and a multidisciplinary endocarditis team (infectious disease, cardiology, neurology, cardiac surgery), which the ESC 2023 guidelines stress more explicitly.^[1][2][3]

Right-sided IE is often managed medically; intervention is considered for persistent bacteremia, very large vegetations (about 20 mm) with recurrent pulmonary emboli, or severe tricuspid regurgitation with right heart failure. Percutaneous vegetation debulking (for example with the AngioVac system) is a bridging option in selected patients, but it does not fix valve dysfunction.^[1]

• Embolic events in about 20 to 30% of patients, with highest risk early and after effective therapy; risk rises markedly with vegetations over 10 mm. Brain and spleen are the commonest sites on the left; septic pulmonary emboli on the right. About 5 to 6% have symptomatic splenic embolism, but CT shows splenic lesions in 19 to 34% of left-sided IE.^[1]
• Heart failure in about 25 to 30% of patients, with about 38% presenting in NYHA class IV; mortality is roughly doubled compared with IE without heart failure (29.7% versus 13.1%).^[1]
• Perivalvular abscess (more common in prosthetic valve IE), often with conduction disturbance such as atrioventricular block; a new conduction abnormality should raise urgent suspicion.
• Valve perforation or rupture in about 13 to 15%, leading to severe regurgitation. ^[1]
• Mycotic aneurysms of cerebral vessels, with rupture carrying 60 to 90% mortality, and intracranial haemorrhage. ^[1]
• Stroke and transient cerebral embolism.
• Immune complex glomerulonephritis.

IE prevention is mostly about oral health, not antibiotics: transient bacteremia arises more often from daily tooth-brushing than from dental visits, so good daily oral hygiene is the most useful step.^[1][2]

Antibiotic prophylaxis before at-risk dental procedures is reserved for high-risk cardiac patients, as summarised below.^[1][2]

Prophylaxis is not routine for bicuspid aortic valve or mitral valve prolapse without other high-risk features, although this point remains debated, with emerging data showing viridans streptococcal IE in some moderate-risk groups.^[1] Routine prophylaxis is also not recommended for non-dental procedures on the current evidence, although links between invasive procedures and IE exist in observational data.^[1]

The two guidelines agree on most points, but differ in emphasis:

• AHA (2015), a scientific statement for adults: sets out diagnostic work-up and organism-directed therapy, clear surgical indications, and prophylaxis rules for high-risk patients. It favours vancomycin plus a third-generation cephalosporin for empiric native valve IE.^[1][2]
• ESC (2023): streamlined empiric therapy (vancomycin-based, without routine gentamicin); explicit endorsement of oral step-down and OPAT in selected stable patients, supported by POET; strong recommendation for early surgical consultation and a multidisciplinary endocarditis team from the outset; PET/CT as Class I in suspected prosthetic valve infection when echo is inconclusive.^[1][3]

Where they disagree on empiric therapy (routine gentamicin in prosthetic valve IE) and on outpatient oral step-down, the topic states both positions rather than picking one.^[1]

Children. IE is uncommon in children without congenital heart disease. Where CHD is present, the site depends on the lesion and oral organisms predominate; dental care is central to prevention.^[1] When IE occurs in a child without an obvious cardiac risk factor, look for underlying congenital heart disease or immunodeficiency.

Pregnancy. IE in pregnancy is rare but serious; it should be managed by a joint obstetric, cardiology and cardiac surgery team. Endocarditis prophylaxis rules are unchanged. Echocardiography is safe and should not be delayed when IE is suspected; antibiotic choices must consider fetal safety.

Older adults. Degenerative valve disease and healthcare exposure make IE more likely in older people. Acute kidney injury limits some regimens, so renal function should guide drug and dose choice, particularly for gentamicin and vancomycin.^[1][2]

People who inject drugs. Right-sided Staphylococcus aureus IE is typical. Empirical cover must include methicillin-resistant strains, with additional cover for Pseudomonas species when Gram-negative organisms are suspected.^[1] Surgery may be deferred in some centres while active drug use continues; multidisciplinary care that includes addiction services improves outcomes and reduces recurrence.

Prosthetic valve and device patients. These patients need a lower threshold for TEE and PET/CT, antibiotic courses of at least 6 weeks, broader surgical criteria, and closer follow-up; recurrence and reinfection rates are higher.^[1][3]

Plain text (no links): this topic sits alongside Cardiology material on valvular heart disease, cardiac imaging and cardiac physical examination. In IE the Cardiology points that matter are the grading and mechanism of valve regurgitation, the difference between a functional murmur and organic regurgitation, the role of transthoracic and transoesophageal echocardiography, echocardiographic features of prosthetic valve dysfunction, indication and timing of valve surgery, and the principles of endocarditis prophylaxis after valve replacement. Where this Infectious Disease account and Cardiology differ in emphasis, the numbers and criteria here are the ones to use for examination, and local Cardiology practice and surgical judgement always take precedence in an individual patient.

In settings where echocardiography, blood culture systems or intravenous therapy may not be available, several points still help:

• Most cases of IE are still diagnosed clinically: prolonged fever, a new or changing murmur, and risk factors such as rheumatic or congenital valve disease, prosthetic valves, injecting drug use or dialysis access. Treat earlier rather than wait for a label, but always take blood cultures first when they are available.
• If culture bottles are unavailable, use sterile technique with whatever aerobic bottle or medium exists and send promptly; negative cultures are common (2.5 to 31%), so clinical diagnosis and serology or molecular testing on resected material when surgery occurs remain valuable.
• Empirical therapy for likely staphylococcal infection is vancomycin if available; where it is not, use the best locally available agent with anti-staphylococcal and anti-streptococcal cover, and monitor kidney function closely if gentamicin is used.
• Surgery is not available everywhere; referral to a cardiac surgical centre should be early for heart failure, uncontrolled infection, large vegetations or systemic embolism.
• Dental prophylaxis is cheap and effective: identify high-risk patients, treat gum disease and dental infection, and give a single oral dose of amoxicillin (or azithromycin or clarithromycin if penicillin-allergic) before dental work involving the gums.
• Rheumatic and congenital heart disease remain the dominant substrates for IE in many low-resource regions, and treating and preventing rheumatic fever remains the long-term prevention.

• IE is infection of the endocardium or heart valves, native or prosthetic, usually bacterial, and it carries mortality of about 15 to 25% even where facilities are good.^[1]
• Fever occurs in up to about 90% of patients; a new or changing murmur in about 85%.^[1]
• Risk factors are prosthetic valves (over 20% of cases), prior IE (about 5% recurrence), congenital heart disease, rheumatic and degenerative valve disease, injecting drug use, and intravascular or dialysis access.^[1]
• Organisms track the setting: viridans streptococci in community-acquired native valve disease (about 18%), Staphylococcus aureus in acute and healthcare-associated disease (26 to 30%), enterococci in older patients, HACEK and fungi in selected groups, Coxiella and Bartonella in culture-negative disease.^[1]
• Vegetations embolise; risk rises sharply once a vegetation exceeds 10 mm. Brain and spleen are the commonest left-sided targets.
• Peripheral clues (Janeway lesions, Osler nodes, splinter haemorrhages, Roth spots, septic emboli, glomerulonephritis) are less common than before but remain diagnostically valuable.
• Take three sets of blood cultures before antibiotics and do transthoracic then transoesophageal echocardiography; TEE sensitivity for vegetations rises from about 50 to 92% in prosthetic valve IE.^[1]
• Use the modified Duke criteria; the 2023 Duke-ISCVID update improved sensitivity from 74.9 to 84.2%.^[1]
• Empirical therapy covers Staphylococcus aureus, streptococci and enterococci (vancomycin plus a cephalosporin for native valves; broader cover for prosthetic or healthcare-associated disease).^[1]
• Definitive courses run 4 to 6 weeks depending on organism and valve type, and at least 6 weeks for prosthetic valve IE.^[1][2][3]
• Surgery is needed in 25 to 50% of patients, most often for heart failure, uncontrolled infection, or large vegetations at risk of embolism; early surgery (within days) is supported for high-risk patients.^[1]
• Prophylaxis is oral hygiene first; antibiotics (amoxicillin 2 g, or azithromycin or clarithromycin 500 mg if penicillin-allergic) only for high-risk cardiac patients before gingival dental work.^[1][2]
• AHA 2015 and ESC 2023 agree on diagnosis and durations but differ on empiric gentamicin and on oral step-down/OPAT.^[1][2][3]