Infective Endocarditis

What is Infective Endocarditis?

Infective Endocarditis (IE) is an infection of the endocardial surface of the heart, usually one or more heart valves or an intracardiac device. IE can be “acute” with rapid and extensive heart valve damage (high virulence) or “subacute” and progress over weeks (low virulence). 

Infective endocarditis is rare, with an incidence of 3-10/100,000. However, with a reported 15-30% in-hospital mortality, it remains an important condition for physicians to know about and recognise.

There are new(ish) predisposing factors, including valve prostheses and intracardiac devices, IV drug use (hopefully less of an issue within our paediatric population, but notable none-the-less), and an increase in the use of invasive procedures at risk for bacteraemia. This is especially important for healthcare professionals, as healthcare-associated infective endocarditis accounts for up to 30% of cases.

SPOT Diagnosis

See if you can recognise some of the classic cutaneous manifestations of subacute bacterial infective endocarditis.

Oslar node on index finger – vasculitis (<10%) 

See also small splinter haemorrhages on fingernail – microemboli (20-40%)

Janeway lesions – septic emboli (<5%)

Osler’s nodes were present in >40% of cases of endocarditis in the pre-antibiotic era. They are now found in <10% of patients with infective endocarditis. The incidence of Janeway lesions has also fallen; you find them in <5% of cases. Petechiae and splinter haemorrhages can be seen in up to 20–40% of cases, but these findings are not specific to IE.

Most common pathogens

Streptococcus viridans, Staphylococcus aureus and coagulase-negative Staphylococci are the most commonly isolated agents.

Less common pathogens include Pseudomonas aeruginosa, Klebsiella oxytoca, the HACEK organisms and Streptococcus pyogenes.

An important fungal cause is Candida albicans.

Staph. aureus is particularly virulent and associated with a higher mortality rate.

Making a diagnosis: The Modified Duke Criteria

In 2023, the European Society of Cardiology (ECS) updated the 2015 guideline describing the Modified Duke Criteria. 

To diagnose DEFINITE IE, a patient must have 2 major OR 1 major + 3 minor criteria OR 5 minor. 

To diagnose POSSIBLE IE, a patient must have 1 major + 1 or 2 minor OR 3-4 minor criteria. 

Major criteria 

I. Blood cultures positive for lE 

a. Typical microorganisms consistent with infective endocarditis from TWO separate blood cultures: 

• Oral Streptococci, Streptococcus gallolyticus (Streptococcus bovis), HACEK group, Staphylococcus aureus, E. faecalis 
• Community-acquired enterococci without a primary focus or 

b. Microorganisms consistent with infective endocarditis from persistently positive blood cultures: 

• ≥2 positive blood cultures of blood samples drawn over 12 hours apart or 
• All of 3 or a majority of ≥4 separate cultures of blood (with first and last samples drawn ≥l h apart); or 

c. Single positive blood culture for Coxiella burnetii or phase I IgG antibody titre > 1:800 

2. Imaging positive for lE 

Valvular, perivalvular/periprosthetic and foreign material anatomic and metabolic lesions characteristic of IE detected by any of the following imaging techniques: 

• Echocardiography (TTE and TOE) 
• Cardiac CT 
• [18F]-FDG-PET/CT(A) 
• WBC SPECT/CT 

Minor criteria 

1. Predisposition from a predisposing heart condition or injection drug use. 

2. Fever (>38°C) 

3. Embolic vascular phenomena (including those detected only by imaging): major arterial emboli, septic pulmonary infarcts, infectious (mycotic) aneurysm, intracranial haemorrhage, conjunctival haemorrhages, and Janeway’s lesions. 

4. Immunological phenomena: glomerulonephritis, Osler’s nodes, Roth’s spots, and rheumatoid factor: 

5. Microbiological evidence: Positive blood culture, but does not meet a major criterion as noted above or serological evidence of active infection with an organism consistent with IE. 

If there is a persisting clinical suspicion of endocarditis but a diagnosis is not yet confirmed, echocardiography should be repeated within 5-7 days, and a trans-oesophageal echo should be considered.

Repeating the microbiological tests is equally important. Blood culture positivity can account for either a major or a minor criterion, so the value of repeated testing must not be underestimated.

Consider further imaging as outlined above (including looking for embolic events), especially in cases of possible prosthetic valve endocarditis.

CASE 1: Left-sided acute infective endocarditis

An 11-year-old male with no past medical history presents to the paediatric ED complaining of left shoulder, neck and knee pain associated with fever for the last seven days.

He appears generally well in himself, with painful movements in his left shoulder.

His CRP is 70, and his ESR is 50.

He is admitted for IV antibiotics (Cefazolin and Gentamicin) and scheduled for a joint aspiration of his knee and shoulder. 

His blood culture and joint aspirates all grow Streptococcus pneumonia.

Of note is that he has a normal echo pre-operatively, and his immune function is also normal. 

Let’s review that first, normal transthoracic echo (TTE).

(HINT: remember these images for later)

The patient was switched to IV Ceftriaxone and is doing extremely well. The plan is for 3-4 weeks of this IV, but after a hypersensitivity reaction after three weeks, he is switched to oral clindamycin and completes a 6-week total course. 

The knee pain recurs two weeks after completing the antibiotics, so antibiotics are restarted for another six weeks. 

The patient returns to the Paediatric ED two weeks after this second course.

This time, he looks very unwell. He has a fever, is vomiting and has had diarrhoea for the last ten days.

The ED team wonder if he has toxic shock syndrome and is concerned.

On examination, he has a new murmur and is complaining of chest pain.



He has a second transthoracic echo.

These findings correlate with clinical examination findings of a “to and fro” murmur indicating aortic regurgitation.

(Look back at the initial echo and compare the two.)

Despite these significant findings, the patient had hyperdynamic LV systolic function with LV fractioning shortening of 44% and an ejection fraction of 73%. 

Let’s consider the chest pain.

A few hours later, the boy starts complaining of severe chest pain.

As his clinical status deteriorates, a second ECG is performed.

Another echo is performed.

His LV function has deteriorated with LV FS at the lower limit of normal (LV fractioning shortening of 27% and ejection fraction of 53%). The patient is admitted to PICU.


A recap of the issues on admission to PICU:

– Acute severe aortic regurgitation
– Aortic root abscess, abscess infra right and infra left coronary arteries with a tear of non-coronary aortic cusp
– Paravalvular abscess 
– Acute myocardial ischaemia
– Early signs of cardiac failure 


Two sets of blood cultures grow Strep. pneumoniae, so we have formal confirmation of infected endocarditis by Modified Duke Criteria (2 x major criteria). 

The initial antibiotic choices are ceftriaxone, clindamycin and vancomycin. This is switched to cefotaxime and rifampicin after input from the infectious disease team. (His earlier hypersensitivity reaction was considered a secondary risk, with the risk of inadequate antibiotic coverage considered more likely to cause harm – no further allergic symptoms were noted). 

He is haemodynamically stable initially, but his complications become increasingly challenging to manage over the next 24 hours, and he develops cardiac failure. This leads to pulmonary oedema and respiratory failure, and he needs ventilation.

He becomes hypotensive, and his lactate rises to 12, so he’s started on vasopressors and inotropes.

Milrinone is commenced to try to improve systemic cardiac output and reduce coronary steal in the context of severe aortic valve incompetence (AI).

Milrinone is a selective phosphodiesterase inhibitor. It has positive inotropic effects and is a vasodilator. It does not have a significant chronotropic effect (on heart rate). It helps in cardiac failure by reducing left ventricular afterload, which results in an increase in cardiac output.

The boy develops multiorgan dysfunction, coagulopathy, transaminitis, and an acute kidney injury. 

Distal sequelae of his left-sided valve disease include a left thalamic ischaemic infarct and splenic infarcts.

A third echo confirms rapid deterioration in systolic function with free aortic regurgitation. A decision is made to operate on his valve. During surgery, he’s found to have near complete destruction of non-coronary and right coronary cusps of the aortic valve.


Emergency aortic root replacement with homograft is performed successfully.

A post-op trans-oesophageal echo (TOE) demonstrates an ischaemic septum with impaired left ventricular function. The new aortic valve is functioning well.

The patient gradually improves in the PICU, and he’s extubated and weaned off inotropic support.

He remains on milrinone for several weeks while his ventricular function improves, and he is then switched to captopril.

He is discharged home on captopril which is later discontinued. He will remain on anticoagulation for life. 

Take away points from case 1 – an acute left-sided IE:

This child had no previous congenital or acquired heart disease.

His risk factor was bacteremia/chronic infection.

He required emergency valve surgery (we will discuss the timing of surgery later).

He had LEFT-sided disease. 

Case 2: Subacute IE

A 14-year-old boy has a history of ASD repair and VSD patch closure.

He has no residual leaks across these defects and has ongoing cardiac follow-up. He has been well for many years since his surgery. He presents to the paediatric ED with unusual upper limb movements.

Of note, he has a history of epilepsy, which is being treated with levetiracetam. His seizure semiology is usually generalized tonic clonic seizures, however he has not had a seizure in over a year. The admitting team reasonably made a diagnosis of focal seizures and admitted him for a neurology review, EEG, and neuroimaging.

The next day, he has another episode (conveniently in the middle of his examination by the neurologist), and it is recognized as a TIA – he has acute upper limb weakness with retained awareness and no seizure movement. 

He has been clinically well and has been afebrile in the hospital; however, he reported a low-grade fever around one week ago and is three months after fixed orthodontics.

A sensible clinician decides to send a blood culture, which grows Strep. Viridans. Multiple blood cultures are sent, all of which are positive. We now have one major criterion met.

His first TTE is completely normal. However, his blood cultures remain persistently positive with no obvious source, so the clinical suspicion remains high.


A second TTE is performed.

We have it! Our second major criterion is met, and SUBACUTE infective endocarditis is diagnosed. Fortunately, the patient remains very well, with no complications. He is managed conservatively and completes six weeks of IV antibiotics. 

Case 3: Right-sided IE

a 9-year-old girl has a history of tetralogy of Fallot, which has been repaired. Her last surgery was when she was an infant, and she has been generally very well. She has an RV-PA conduit with a contegra conduit. 

She is admitted via the cardiology outpatients with pulmonary valve endocarditis, which is causing progressive moderate to severe pulmonary stenosis (peak gradient 60mmHg) and severe pulmonary regurgitation. 

Her blood cultures grow Staph. aureus (our two major criteria are met once again). She is treated with antibiotics for one month and has elective surgery for an RV-PA homograft.

During her admission, she has a CTPA to rule out pulmonary embolisms.

The summary of her case:

• Prosthetic material increases the lifetime risk of IE
• Acute endocarditis
• Right-sided disease – severe pulmonary regurgitation is tolerated better than severe aortic regurgitation.
• Sequalae from the right-sided disease include pulmonary emboli (fortunately not in this case)
• Once the infection was treated, elective surgery was performed on her valve

The diagnostic challenge

The clinical history of infective endocarditis is highly variable. The causative microorganism and existence or absence of pre-existing cardiac disease manifest differently. The diagnosis is often more difficult in patients with a prosthetic valve or intracardiac device and in those with blood culture-negative IE (BCNIE).

While the Duke criteria are useful for classification, they have limited value in some subgroups, e.g., cardiac device-related IE (CDRIE), prosthetic valve IE (PVE), and BCNIE. Clinicians must ensure that binary criteria do not replace clinical judgment. 

Both echocardiography and blood cultures are the cornerstones of diagnosis in cases of IE.

If persisting high level of clinical suspicion, for example due to a new pathological murmur, ECG changes or a suspicious organism on blood culture, the echo and blood culture should be repeated, and other imaging techniques should be used to detect silent vascular phenomena.

For example, imaging modalities to detect cardiac involvement include cardiac CT, 18F-FDG PET/ CT, or leukocytes-labelled SPECT/CT, and imaging to detect embolic events, i.e., cerebral MRI, whole-body CT, and/or PET/CT. 

Management Strategy for Infective Endocarditis

Management includes prolonged antimicrobial therapy and possible surgical eradication of the infected tissues. PVE needs longer treatment (at least six weeks), while native valve endocarditis (NVE) needs 2 to 6 weeks. The duration of therapy is based on the first day of effective antibiotic therapy, not on the day of surgery.

Indications for surgery

There are three main indications for early surgery in infective endocarditis. They are the three main complications: heart failure, uncontrolled infection and prevention of embolic events.

Heart failure is the most frequent and severe complication of IE. Unless there is a severe comorbidity, the development of heart failure is an indication for early surgery.

Uncontrolled infection most frequently relates to the perivalvular extension of infection or a “difficult-to-treat” organism. Unless there is a severe comorbidity, uncontrolled infection is another indication for early surgery. 

Emboli occur in 20-50% of cases of infective endocarditis. The risk of embolism is related to the size and mobility of the vegetation and is the highest during the first two weeks of antibiotics. This risk is reduced with an early surgical strategy for vegetations with a high risk of embolism. It is important to consider right versus left-sided disease when balancing the risk of acute surgery against the consequence of either a pulmonary embolism or an ischemic cerebral vascular event. If a patient has already had a neurological complication, surgery is generally delayed.

Symptomatic neurological events

Symptomatic neurological events develop in 15–30% of all patients with IE. Additional silent events are common.

Stroke (ischaemic and haemorrhagic) is associated with increased mortality. Therefore, rapid diagnosis and initiation of appropriate antibiotics are important to prevent a first or recurrent neurological complication.

Anti-coagulation is generally not indicated in ischaemic strokes in the context of IE, as these patients are believed to be particularly susceptible to haemorrhagic transformation of embolic lesions.

If there has been intracranial haemorrhage, the neurological prognosis is worse, and surgery should generally be postponed for at least one month.

Surgical Management 

50% of cases of acute IE require surgical treatment, so early consultation with a cardiac surgeon is recommended. Identifying patients requiring early surgery is frequently difficult and is an important scope of the ‘Heart Team.’ 

A multidisciplinary team approach reduces 1-year mortality. This is key for complicated IE, i.e. endocarditis with heart failure, abscess, embolic or neurological complication or CHD. These patients should be referred to a surgical centre early.

Non-complicated IE can initially be managed locally, ensuring consultation with the multidisciplinary ‘Endocarditis Team’ +/- external visit to the reference centre for review. 

Characteristics of the Referral Centre

The referral centre should have access to diagnostic procedures, including TTE, TOE, multislice CT, MRI, nuclear imaging and neuroradiology to interpret these scans.

Specialities on site (the ‘Endocarditis Team’) should include cardiac surgery, cardiology, infectious disease, microbiology, and neurology.

When to get an echo

A transthoracic echo (TTE) is recommended in suspected infective endocarditis, e.g., if blood culture is positive or minor criteria are present. A transesophageal echo (TOE or TEE if you are from overseas) is recommended in patients with high clinical suspicion of IE and a normal TTE.

The TTE or TEE should be repeated within 7-10 days in cases of initially negative examination when clinical suspicion of IE remains high. 

TEE is not indicated in patients with a good-quality negative TTE and low clinical suspicion.

Remember—if endocarditis is suspected, the most important test is good-quality, large-volume (and repeated) blood cultures.

The Pendulum of Antibiotic Prophylaxis…

A 2008 NICE guideline recommended that people at risk of infective endocarditis having interventional procedures* should not be offered antibiotic prophylaxis against infective endocarditis. This represented a marked change from previously accepted practice.

In 2014, the Lancet published a paper reporting an increase in cases of infective endocarditis from 2000 to 2013. NICE assessed the new evidence, including this paper, and, in 2015, published an update of its guidelines. 

*Interventional procedures = upper and lower respiratory tract procedures, upper and lower gastrointestinal tract procedures, genitourinary tract procedures.

The current status:

‘Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.’

The word “routinely” was added to the 2015 guideline after a 2014 Lancet paper suggested that the introduction of the 2008 guideline may have affected the incidence of infective endocarditis in the UK. However, this increase in incidence was also noted in countries still using antibiotic prophylaxis.

The new guideline allows clinical judgement, with the word “routinely” leaving room for case-to-case decisions.

A Cochrane review found insufficient evidence to determine whether antibiotic prophylaxis is effective or ineffective in people at risk of IE who are about to undergo an invasive dental procedure.

NICE published a guideline in 2015 that outlines which patients were at an “increased” risk of IE and which patients were part of the subgroup that required “special consideration” regarding antibiotic prophylaxis. Those in the special considerations subgroup were (as well as being at increased risk of IE) considered to be at particularly high risk of developing serious and potentially life-threatening complications and, therefore, may require “non-routine” management. 

The groups who are recognised to be at an increased risk of IE include those with valvular heart disease, hypertrophic cardiomyopathy, previous IE, and structural congenital heart disease (excluding an isolated ASD or fully repaired VSD/PDA with closure devices considered to be endothelialised). 

However, the subgroup that requires “non-routine” management and, therefore, should receive antibiotic prophylaxis for invasive procedures includes those with prosthetic valves or cases where prosthetic material was used for valve repair, previous endocarditis, any cyanotic congenital heart disease, and any congenital heart disease with prosthetic material (for six months after the procedure or life-long if there is a residual shunt or valve regurgitation remains).

European and American guidance differs slightly. In Europe, the ESC Guidelines for the Management of Infective Endocarditis (2015) recommends antibiotic prophylaxis only for “patients at highest risk for endocarditis…undergoing at risk dental procedures…and is not recommended in other situations.”

In America, on the other hand, the AHA guideline Prevention of Infective Endocarditis (2007) says, ‘

In patients with underlying cardiac conditions associated with the highest risk of adverse outcomes from IE… IE prophylaxis for dental procedures is reasonable, even though we acknowledge its effectiveness is unknown.’  

Although there are subtle differences in the guidance, all agree on special considerations for those at the HIGHEST risk (and therefore, prophylaxis is not routinely recommended for those only in the high-risk category).

Oral Bacteria

The traditional opinion of oral bacteria’s impact was that high-grade bacteraemias occur during invasive dental procedures, representing the highest risk of developing IE. The consequence was higher rates of antibiotic prophylaxis.

Newer evidence suggests that cumulative, low-grade bacteraemias cause more impact, e.g. normal daily activities such as tooth brushing, flossing and chewing. Daily oral hygiene is more important than ad hoc antibiotics.

Remember: Oral streptococci are implicated in 45% of IE cases.

Recent reports suggest the proportion of endocarditis cases involving oral streptococci has fallen. 2-5% of endocarditis patients had dental procedures in the 3-12 months before their diagnosis. 

The Principles of Prevention of IE

Other important preventative measures should be taken, along with antibiotic prophylaxis for invasive procedures (including dental procedures) for those in the subgroup at the highest risk of endocarditis. 

Good oral hygiene and regular dental review are more important than antibiotic prophylaxis in reducing the risk of IE. Clinicians should follow aseptic precautions during any procedures that may cause transient bacteremia, e.g., venous catheters, to reduce the rates of healthcare-associated IE. We should be mindful to adhere to care bundles for central and peripheral cannulae and limit the use of invasive procedures where possible. 

Non-specific prevention measures should be applied to the general population, particularly to high-risk patients. This includes twice-yearly dental reviews, curative antibiotics for any focus of bacterial infection, eradication of chronic bacterial carriage, and strict asepsis for at-risk procedures. Patients in this group should be discouraged from getting a piercing or tattoo. 

What antibiotic should be used for prophylaxis?

The first line in children is amoxicillin 50mg/kg (oral or IV, to a max of 2g) as a single dose 30-60 minutes before the procedure.

Clindamycin 20mg/kg (oral or IV to a max of 600mg) may be used in children allergic to penicillin.

Does antibiotic prophylaxis in those at risk of developing infective endocarditis reduce the incidence of infective endocarditis?

Well, we don’t really know.

Limited evidence exists regarding the effectiveness of antibiotics. Current evidence includes limited data from observational studies with inconclusive findings. 

Ideally, we would have an RCT with long-term follow-up of antibiotic prophylaxis versus no antibiotic prophylaxis in adults and children for those with underlying structural cardiac defects. We could then compare the incidence of IE and adverse effects, including anaphylaxis. However, this comes with many logistical challenges, including a low incidence of CHD and a lower incidence of IE within this group.

Take home message

Fever and a murmur do not equal infective endocarditis. 

There has been an increase in IE due to Staphylococcus and healthcare-associated IE. Ensure aseptic measures for procedures at risk of causing bacteremia.

IE in patients without previously known heart disease accounts for an increasing incidence.

Preventive measures must be taken for all patients, especially those with cardiac disease)

Antibiotic prophylaxis is only for the highest-risk (not “high” risk) IEs undergoing the highest-risk dental procedures.

Oral hygiene and regular dental review are more important than antibiotic prophylaxis to reduce risk.

References

Centre for Clinical Practice at NICE (UK, 2008. Prophylaxis Against Infective Endocarditis: Antimicrobial Prophylaxis Against Infective Endocarditis in Adults and Children Undergoing Interventional Procedures [Internet].

Dayer, M.J., Jones, S., Prendergast, B., Baddour, L.M., Lockhart, P.B. and Thornhill, M.H., 2015. Incidence of infective endocarditis in England, 2000–13: a secular trend, interrupted time-series analysis. The Lancet, 385(9974), pp.1219-1228.

Delahaye, F., M’Hammedi, A., Guerpillon, B., de Gevigney, G., Boibieux, A., Dauwalder, O., Bouchiat, C. and Vandenesch, F., 2016. Systematic search for present and potential portals of entry for infective endocarditis. Journal of the American College of Cardiology, 67(2), pp.151-158.

Delgado, V., Ajmone Marsan, N., de Waha, S., Bonaros, N., Brida, M., Burri, H., Caselli, S., Doenst, T., Ederhy, S., Erba, P.A. and Foldager, D., 2023. 2023 ESC Guidelines for the management of endocarditis: Developed by the task force on the management of endocarditis of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS) and the European Association of Nuclear Medicine (EANM). European heart journal, 44(39), pp.3948-4042.

Demir, F., Varan, C., Erdem, S., Atmış, A., Akbaş, T., Subaşı, B., Güzel, Y. and Özbarlas, N., 2023. Infective endocarditis in childhood: a single-centre experience of 26 years. Cardiology in the Young, 33(10), pp.1950-1955.

Glenny, A.M., Oliver, R., Roberts, G.J., Hooper, L. and Worthington, H.V., 2013. Antibiotics for the prophylaxis of bacterial endocarditis in dentistry. Cochrane Database of Systematic Reviews, (10).

Gogos C, Moschovidis V, Adamopoulos C, Trigoni A, Styliadis I, Sachpekidis V. A case series of skin manifestations of infective endocarditis in contemporary era: just another book finding or a useful clinical sign? Eur Heart J Case Rep. 2021 Aug 20;5(9):ytab345. doi: 10.1093/ehjcr/ytab345. PMID: 34557639; PMCID: PMC8453381.

Habib, G., (France), Badano, L., (Italy), Tribouilloy, C., (France), Vilacosta, I., (Spain), Zamorano, J.L., (Spain) and Galderisi, M., 2010. Recommendations for the practice of echocardiography in infective endocarditis. European Journal of Echocardiography, 11(2), pp.202-219.

Habib, G., Lancellotti, P., Antunes, M.J., Bongiorni, M.G., Casalta, J.P., Del Zotti, F., Dulgheru, R., El Khoury, G., Erba, P.A., Iung, B. and Miro, J.M., 2015. 2015 ESC guidelines for the management of infective endocarditis: the task force for the management of infective endocarditis of the European Society of Cardiology (ESC) endorsed by: European Association for Cardio-Thoracic Surgery (EACTS), the European Association of Nuclear Medicine (EANM). European heart journal, 36(44), pp.3075-3128.

Philip, M., Tessonier, L., Mancini, J., Mainardi, J.L., Fernandez-Gerlinger, M.P., Lussato, D., Attias, D., Cammilleri, S., Weinmann, P., Hagege, A. and Arregle, F., Comparison Between ESC and Duke criteria for the diagnosis of prosthetic valve infective endocarditis. JACC Cardiovasc Imaging. 2020; 13 (12): 2605–15