24th June 2026

Infective Endocarditis

Background 

Infective endocarditis (IE) is an infection involving the endocardium, including the heart valves, chordae tendineae, and sites of existing defects, such as a septal defect. It is a rare condition, with an incidence of 10 per 10,000 in the general population, and carries a high morbidity and mortality, and therefore prompt recognition and treatment is essential. It may affect native heart valves or prosthetic heart valves. 

Epidemiology

Risk factors for the development of IE are: 

• Structural heart disease (including HOCM, ASD, VSD, PDA, ToF)
• Valvular heart disease (including previous rheumatic fever)
• Presence of a prosthetic valve (including TAVI)
• Poor dental hygiene
• Age >60
• Male sex (three times more common in men)
• Immunosuppression (including cytotoxic medications, HIV)
• Intravenous drug use (IVDU)
• Previous IE
• Indwelling intravascular devices 
• Presence of implantable cardiac devices 
• Chronic haemodialysis 

IE may be classified as right-sided (tricuspid and pulmonary valves) or left-sided (aortic and mitral valves). It may affect the patient’s own valves (native-valve IE) or a prosthetic valve. Left-sided IE is more common than right-sided. Right-sided IE is particularly associated with IVDU, and the tricuspid valve is particularly vulnerable in these cases. One in six patients with a prosthetic valve will develop IE, and this population makes up approximately 20% of all cases of IE.

Aetiology     

IE is caused by bacteraemia in association with valvular damage, and the subsequent formation of vegetations on valve leaflets and other endothelial structures. Damage may occur due to an underlying valvular condition, degeneration of the valve, the infective organism itself, or due to trauma (such as from foreign material). Damage to the endothelium leads to platelet and fibrin aggregation, providing a surface for the circulating microorganism to bind to. This leads to further aggregation of platelets and fibrin, eventually resulting in the formation of a vegetation. 

IE is most commonly caused by bacterial infection, but fungal infections may also occur. In native-valve IE (NVIE), the commonest causative pathogens world-wide are staphylococci, streptococci, and enterococci. Other, rarer, pathogens may also be implicated. Right-sided IE (90% of which is related to IVDU) is usually caused by staphylococcus aureus, which accounts for up to 90% of cases. Table 1 summaries the microorganisms implicated in IE, and their associations. 

In prosthetic-valve IE (PVIE), the commonest responsible pathogens can be predicted depending on the length of time since the valve was placed:

• < 2 months post-procedure: staphylococcus aureus and coagulase-negative staphylococci. 
• 2 – 12 months post-procedure: coagulase-negative staphylococci and streptococci. 
• > 12 months post-procedure: the spectrum of causative organisms is similar to that in NVIE. 

Additionally, in patients with prosthetic valves in situ, IE may develop due to seeding on the prosthetic valve from a bacteraemia of any other source, and this is important to keep in mind in unwell patients with prosthetic valves. 

In some cases, patients with IE may have negative cultures (culture-negative IE). This may be due to patients receiving antibiotics prior to blood cultures being taken, but is also associated with specific microorganisms, and therefore additional serological testing may be required to identify the causative organism. Bacteria associated with culture-negative IE are:

• HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium, Eikenella, Kingella)
• Coxiella burnetii
• Chlamydia species
• Bartonella species 
• Legionella

Table 1: pathogens associated with IE and their characteristic associations

Diagnosis

The diagnosis of IE should be based on a combination of signs, symptoms, and investigation results.

Clinical Manifestations

The clinical presentation of IE is extremely variable; it may present with acutely unwell and deteriorating patients, or as a sub-acute condition with non-specific symptoms. 

Common signs and symptoms of patients with IE are those of infection: 

• fever (seen in approximately 90% of patients)
• chills 
• anorexia
• weight loss 
• fatigue
• myalgias
• arthralgia
• night sweats
• dyspnoea
• headache
• symptoms related to the cause may also be present, such as toothache

Clinical signs that may be elicited on examination include: 

• heart murmurs (seen in 85% of patients with IE)
• splenomegaly
• petechiae
• splinter haemorrhages 
• Janeway lesions
• Osler’s nodes
• Roth spots
• heart failure (due to valvular incompetence)
• neurological symptoms (due to septic emboli, intracranial haemorrhage or cerebral abscess)

Image Source: Wikimeadia Commons (2017). January Lesion, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Janeway_lesion.JPG (Accessed 2 May 2025)

Image Source: Wikimedia Commons (2017). Osler’s Nodes, Licensed under a creative commons licence. Available for free at: https://commons.wikimedia.org/wiki/File:Osler_Nodules_Hand.jpg (Accessed 2 My 2025)

If septic emboli are involved, patients may have signs consistent with renal or splenic infarction, or may have signs consistent with an infective source of the IE (septic arthritis, psoas abscess, osteomyelitis). 

In patients presenting with subacute IE, the symptoms may be vague and non-specific, and a high degree of suspicion is required to make the diagnosis. Patients may present with congestive heart failure or a stroke with no other symptoms suggestive of endocarditis. 

In patients with a prosthetic valve, whilst the presenting features may be similar to those in patients with NVIE, there are some particular features to be aware of. The frequency of new murmurs, a changing murmur, and presence of conduction defects on an ECG are seen more frequently in patients with IE with a prosthetic valve.

Investigations

All patients with suspected IE should have the following investigations: 

• Blood cultures: at least 3 sets, ideally before antibiotics are given, taken from separate sites 
• Bloods including WCC, U&Es and CRP/ESR
• ECG: looking for PR prolongation, which may be seen in the presence of an aortic root abscess
• Urine dip: evidence of renal failure 
• Chest x-ray
• Trans-thoracic echocardiogram (TTE): first-line imaging investigation for IE

Other investigations to consider are: 

• Trans-oesophageal echocardiogram (TOE): may be required if IE suspected but initial TTE is negative
• CT chest: indicated if an aortic root abscess is suspected; may also be required preoperatively in patients requiring surgical management 
• Serological testing for culture negative organisms 
• Other imaging to look for soft tissue abscess/vertebral osteomyelitis/evidence of septic emboli may also be required

Image Source: Wikimedia Commons (2017). Infective Endocarditis, Licensed under a creative licence. Available for free at: https://commons.wikimedia.org/wiki/Category:Bacterial_endocarditis (Accessed 2 May 2025)

Diagnostic Criteria

The diagnosis of IE is made based on the modified Duke’s criteria, outlined in the table below. A definite diagnosis of IE is defined as the presence of: two major criteria; one major and three minor criteria; or five minor criteria. A possible diagnosis is defined as: one major and one minor criterion or; three minor criteria. These are summarised in table 2:

Table 2: modified Duke criteria for infective endocarditis

Medical Management

The mainstay of medical management of IE is antimicrobial therapy, as well as other supportive measures.

Antimicrobial therapy

Antibiotic therapy should be targeted based on the microorganism isolated from the blood cultures.  If patients are acutely unwell, empirical antibiotics should be commenced, however, this should be after at least two (preferably three) sets of blood cultures have been taken. The appropriate empirical antibiotic regimen depends on whether the valve in native or prosthetic, and depends on the likely causative microorganism, as summarised in Table 3. 

Duration of therapy in NVIE is generally four to six weeks, whilst in PVIE the duration is usually a minimum of six weeks, and additional surgical management is often required.

Table 3: recommended empirical antibiotics in infective endocarditis

Antimicrobial prophylaxis

Antibiotic prophylaxis is no longer recommended routinely for patients undergoing dental procedures, or for patients undergoing procedures involving the GI tract, genitourinary tract (including gynaecological and obstetric procedures), or the upper and lower respiratory tracts. However, for patients deemed to be at the highest risk for developing IE, antibiotics prophylaxis may be considered for dental procedures, procedures involving the respiratory tract, procedures involving skin and soft tissues, and cardiac surgery involving implantation of prosthetic material. The table below summaries those patients who would be deemed to be at the highest risk of developing IE. 

Patients considered to be at high risk are those with the following conditions: 

• acquired valve disease (stenosis or regurgitation); 
• hypertrophic cardiomyopathy; 
• previous IE, 
• structural congenital heart disease (excluding isolated ASD, fully repaired VSD or PDA, and closure devices that are fully incorporated into the endothelium)
• patients with a prosthetic valve.

Antithrombotic therapy

Patients are at high risk of thrombotic events from septic emboli, and subsequently high risk for bleeding (including intracerebral haemorrhage), and therefore routine anti-platelet and anticoagulant therapy is not advised in patients with IE, and has not been shown to reduce the risk of embolic complications.

Surgical Management

Indications for surgical management in IE are: 

• Heart failure
  • Left-sided IE causing heart failure; severe valve regurgitation with no heart failure
  • Right-sided IE: tricuspid regurgitation causing heart failure that is refractory to medical therapy
• Infection
  • Persistent bacteraemia despite adequate antimicrobial therapy
  • Formation of an abscess, false aneurysm, or enlarging vegetation
  • Fungal infection or infection with multi-resistant organism
• Prevention of embolic complications
  • Left-sided IE with large vegetations (>10mm) resulting in one or more embolic episodes despite appropriate antimicrobial therapy
  • Isolated vegetations >15mm

Complications 

There are many possible complications of IE, some related to the progression of the condition, and others related to its treatment. 

Complications related to septic emboli and spread of infection

• Mycotic aneurysm formation
• Metastatic abscesses: most commonly occur in the kidneys, spleen, brain, and soft tissues
• Stroke
• Septic arthritis
• Vertebral osteomyelitis
• Meningitis – patients with staph aureus IE are particularly susceptible to this
• Pneumonia, lung abscess and pleural effusions

Complications related to treatment 

• Glomerulonephritis
• Acute interstitial nephritis 

Other complications

• Heart failure
• Valvular incompetence
• Pericarditis
• Encephalopathy 
• Meningoencephalitis
• Cerebral haemorrhage (secondary to stroke or aneurysm formation)

References

• https://www.nice.org.uk/guidance/cg64/ifp/chapter/infective-endocarditis 
• https://bestpractice.bmj.com/topics/en-gb/3000215
• https://www.nice.org.uk/guidance/cg64/ifp/chapter/infective-endocarditis 
• https://www.nice.org.uk/guidance/cg64/ifp/chapter/infective-endocarditis 
• https://www.uptodate.com/contents/native-valve-endocarditis-epidemiology-risk-factors-and-microbiology?search=native%20valve%20endocarditis&source=search_result&selectedTitle=5~150&usage_type=default&display_rank=5
• https://www.uptodate.com/contents/prosthetic-valve-endocarditis-epidemiology-clinical-manifestations-and-diagnosis
• https://www.uptodate.com/contents/right-sided-native-valve-infective-endocarditis?search=native%20valve%20endocarditis&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4
• https://www.uptodate.com/contents/clinical-manifestations-and-evaluation-of-adults-with-suspected-left-sided-native-valve-endocarditis?search=native%20valve%20endocarditis&source=search_result&selectedTitle=2~150&usage_type=default&display_rank=2
• https://www.uptodate.com/contents/overview-of-management-of-infective-endocarditis-in-adults?search=native%20valve%20endocarditis&source=search_result&selectedTitle=1~150&usage_type=default&display_rank=1
• https://www.nice.org.uk/guidance/cg64/ifp/chapter/infective-endocarditis 
• https://patient.info/doctor/infective-endocarditis-pro#nav-2