Clinical review of infective endocarditis: diagnosis and management

The diagnosis and management of infective endocarditis, including investigations such as blood cultures and echocardiography and European Society of Cardiology guidelines for managing the condition.

Bacterial andocarditis (Photo: SPL)
Bacterial andocarditis (Photo: SPL)

Section 1 Epidemiology and aetiology

Infective endocarditis (IE), a microbial infection of the endothelial surface of the heart, most commonly affects the valve leaflets and carries increased morbidity and mortality.

IE can also occur on foreign material, such as permanent pacemaker leads and prosthetic cardiac valves and grafts. Management of prosthetic valve endocarditis is particularly challenging.

The characteristic lesion of IE is a vegetation, a mass of platelets in which micro-organisms and inflammatory cells are enmeshed. This may be visible on echocardiography and may embolise, leading to infarction and seeding of infection.1

The clinical presentation varies considerably and is dependent on the organism involved, the site of infection, any underlying cardiac disease and the patient's immune response. It may therefore present acutely to hospital with sepsis, heart failure and evidence of embolisation, or more insidiously in primary care with persistent fever and malaise.

Acute IE is typically caused by Staphylococcus aureus (the commonest pathogen), whereas the subacute variety can be caused by viridans streptococci, enterococci, coagulase-negative staphylococcus and Gram-negative coccobacilli. Sometimes, there is an identifiable source of bacteraemia (such as a dental procedure or indwelling venous line).1

Epidemiology, classification
The epidemiology of endocarditis has changed significantly in recent years.2 Traditionally, it was seen in younger patients with rheumatic valve disease. As rheumatic fever declines in industrialised nations, it is increasingly a disease of the elderly and those with prosthetic heart valves or cardiovascular implantable devices.

The overall incidence was thought to have remained steady over the past 30 years, with about three to 10 episodes per 100,000 person-years, rising to 14.5 episodes per 100,000 person-years in those aged 70-80 years. Recent evidence suggests that the incidence may be rising over the last 5 years; the reason for this remains unknown.3

Increasing longevity has led to the emergence of degenerative heart disease, particularly calcific aortic stenosis, as a major predisposing factor. Nosocomial endocarditis is also occurring more often. The increasing use of indwelling venous lines for acute hospital treatment and long-term renal dialysis is implicated.

IE is commonly classified according to its speed of onset (acute vs subacute), according to site (left- or right-sided) or into native or prosthetic valve/prosthetic device IE. It may also be defined by the route of acquisition (healthcare associated with or without indwelling lines, community acquired or from IV drug use).

Section 2 Making the diagnosis

The presenting features are varied and delayed diagnosis is common.The condition may be acute and fulminant, or subacute and chronic. Most patients (90%) will have fever and malaise, often with weight loss. Most have heart murmurs (85%), although the classical 'changing murmur' is rarer. New regurgitation murmurs are highly suspicious.

Classical features of IE may be present in up to 50% of patients. These include splinter haemorrhages under the fingernails, Janeway lesions, Osler's nodes, Roth's spots or finger clubbing. These stigmata are less frequent in earlier presentations of the disease.

Patients may also present with stroke, or peripheral or pulmonary emboli as vegetations break away. A high index of suspicion is appropriate in patients with prosthetic valves, pacemakers and indwelling lines.1

Investigations include routine blood tests, blood cultures and transthoracic echocardiography. The blood test may show anaemia of chronic disease, leucocytosis, renal failure and a high CRP and ESR.

The blood cultures require three 10ml samples from different sites at different times with meticulous aseptic technique, before administration of antibiotics. Yield from appropriately taken cultures is high. If cultures remain negative, microbiologists can advise on special media or special microbiological techniques for organism identification, such as PCR.

Transthoracic echocardiography (TTE) has a sensitivity of about 50% and transoesophageal echocardiography (TOE), more than 90%.

Vegetations, abscesses, valve regurgitation and prosthetic valve dehiscence may be seen. Infection on pacing leads is more difficult to visualise. A TTE is advised as the initial test, followed by TOE in the majority of cases of suspected or positive TTE. In cases of negative or non-diagnostic TTE, a TOE should always be performed. Other imaging techniques may be of use in specific settings (for example CT). 

The Duke criteria (see box 1) are commonly used in clinical practice. They do not replace clinical judgment. Diagnosis requires two major criteria, one major and three minor, or five minor criteria.4

Box 1: Modified Duke criteria

Major criteria

1. Blood cultures positive for IE:

  • Typical microorganisms consistent with IE from 2 separate blood cultures.
  • Microorganisms consistent with IE from persistently positive blood cultures.

2. Imaging positive for IE:

  • Echocardiogram positive for IE.
  • Abnormal activity around the site of prosthetic valve implantation detected by 18F-FDG PET/CT or radiolablelled leukocytes SPECT/CT.
  • Definite paravalvular lesions by cardiac CT.

Minor criteria

1. Predisposition such as predisposing heart condition, or injection drug use.

2. Fever defined as temperature >38 degrees C

3. 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 organism consistent with IE.

Section 3 Managing the condition

The basis of treatment is prolonged combined bactericidal antibiotic therapy along with surgical intervention when indicated.

Antibiotics should be initiated once blood cultures are taken. Early determination of the organism and sensitivities allows adjustment of therapy, especially as resistance is increasing.1

Therapy usually lasts two to six weeks for native valve IE (NVE)  and six weeks or more for prosthetic valve IE (PVE). A multidisciplinary approach in treatment is important, including cardiology, cardiothoracic surgery and microbiology input, as well as access to imaging such as multi slice CT and MRI.4

If a valve is replaced surgically, the duration of treatment is measured from the first day of effective antibiotic administration, unless the valve culture is positive. Synergistic combinations of antibiotics are used to maximise effect. Aminoglycosides shorten the therapy duration.4

The 2015 European Society of Cardiology guidelines gave full details of recommended antibiotic regimens.4 Most regimes comprise of a penicillin for four to six weeks, with an aminoglycoside (gentamicin) for up to two weeks, although in streptococcal NVE, treatment may be shorter.

Staphylococcal IE, either NVE or PVE, is treated with either flucloxacillin or vancomycin with rifampicin and gentamicin. The indications and use of aminoglycosides have changed and they are given once daily owing to renal toxicity.

ESC also advocates use of antibiotics as prophylaxis to limit the risk of IE in the highest risk patients undergoing dental procedures. Prophylaxis is not recommended for any other type pf procedure (such as respiratory tract, gastointestinal, or urological procedures).NICE does not recommend antibiotic prophylaxis in any patient.5

Box 2: European Society of Cardiology guidelines

Antibiotic prophylaxis must be limited to patients with the highest risk of IE undergoing the highest risk dental procedures (dental procedures requiring manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa): 

1. Patients with a prosthetic valve, including trans catheter valve, or prosthetic material used for cardiac valve repair.

2. Patients with previous IE.

3. Patients with congenital heart disease:

- any cyanotic congenital heart disease.

- congenital heart disease repaired with prosthetic material whether placed surgically or percutaneous techniques, up to 6 months after the procedure or lifelong if there remains residual shunt or valvular regurgitation. 

Despite antibiotic treatment, up to half of patients with IE will require valve surgery. This carries considerable risk, but can be lifesaving.

Surgery may be required acutely, but if possible, should be delayed for valve sterilisation with antibiotics (usually at least two weeks).

Indications for surgery include:

  • heart failure (refractory pulmonary oedema, cardiogenic shock)
  • uncontrolled infection (abscess, enlarging vegetation, persistent cultures)
  • prevention of embolism in certain clinical situations.

Managing PVE and Cardiac Device Related IE (CDRIE)
The diagnosis of PVIE and CDRIE is more challenging because blood cultures may be negative and interpreting the echocardiogram difficult.

PVE makes up 20% of all IE cases. Early PVE (less than 1 year postoperation) is often caused by nosocomial  infection with staphylococci Gram-negative organisms and fungi; late PVE more closely mirrors the  microbioligical profile of NVE.1 Early PVIE is usually managed surgically  in high risk subgroups because antibiotic therapy is rarely effective.5

Streptococcal late PVE may be managed medically, but these patients have to be carefully monitored due to the risk of relapse.

CDRIE may be localised to the generator pocket, with local erythema and swelling, or may effect the pacing leads in the right-sided heart chambers and valves. Staphylococcal species are the most common culprits.

Treatment is with IV antibiotics for four to six weeks and the device leads must be removed. Re-implantation of the device is best delayed, if possible, until the infection is treated. It carries a poor prognosis as it frequently occurs in elderly patients with multiple comorbidities. 

Section 4 Prognosis and complications

Overall inpatient mortality from endocarditis varies from 15-30%.1 Those at highest risk should be managed in a specialist centre with full input from the 'endocarditis team'. 

The major determinants of poor outcome are patient characteristics (old age, prosthetic valve, diabetes), complications (stroke, renal or heart failure), the infecting organism (Staph aureus and fungi carry worse prognosis) and echocardiographic findings, such as vegetation size and valve dysfunction or dehiscence. If three adverse factors are present, mortality approaches 79%.

Complications include recurrent infection (which may be a relapse with the same organism, or reinfection - about 1.3% per patient-year), heart failure, need for valve surgery, embolic events (such as stroke) and death. Causes of recurrence include inadequate antibiotic treatment and persisting sources of bacteraemia (such as periodontal abscess).2

Section 5 Case study

An 80-year-old woman presented to her GP with three weeks of intermittent fevers.

She felt generally tired and had noticed worsening breathlessness on exertion. She had type 2 diabetes and hypertension and was taking metformin, perindopril and amlodipine.

On examination, her temperature was 38.2 degrees C with a regular pulse at 90bpm. BP was 110/62mmHg and there was an early diastolic murmur. The lung fields were clear and there was minimal ankle oedema. Urine dipstick revealed blood and glucose.

She was referred to hospital; blood tests revealed anaemia (Hb 102g/L), leucocytosis (WCC 14.8 x 109/L), renal failure (urea 14.6mmol/L, creatinine 180 micromol/L) and raised CRP (207mg/L).

A chest X-ray was normal and a set of blood cultures was taken in A&E and a further two sets on the ward. The patient was started on empirical antibiotics for endocarditis (IV augmentin and gentamicin).

The following day, transthoracic echocardiography confirmed severe aortic regurgitation (AR) with a moderately dilated left ventricle and preserved systolic function.

She went on to have TOE, which confirmed severe AR and a small mobile vegetation on the right coronary cusp of the aortic valve.

The patient remained stable, but with continuing spikes of fever and high inflammatory markers. The next day, blood cultures grew Strep bovis with full sensitivity and her antibiotics were changed to amoxicillin and gentamicin after microbiology advice, with careful monitoring. 

Five days later, she developed a left hemianopia, which resolved after one hour. CT brain was normal and repeat TOE showed the vegetation was now more than 1cm in length. 

A decision was made to operate acutely, due to progressive infection with embolisation and a large vegetation despite antibiotic therapy. A bioprosthetic aortic valve was implanted and antibiotics continued for four weeks. Once recovered, she had a colonoscopy due to the association between Strep bovis and colorectal cancer.

Section 6 Evidence base


Further resources

  • Daniel WG, Flachskampf FA. Infective endocarditis. In: Camm AJ, Luscher TF, Serruys PW (eds). The ESC Textbook of Cardiovascular Medicine. Oxford, OUP, 2009
  • Rosendorff C (ed). Essential cardiology: principles and practice (third edition). London, Springer, 2013 

Original article by Dr Simon Pearse, clinical research fellow in cardiology, Royal Brompton Hospital, London, and Dr Constantinos Missouris, consultant cardiologist, Wexham Park Hospital, Slough, Berkshire, and senior lecturer, Royal Brompton Hospital London.

Article updated in 2016 by Dr Constantinos Missouris, Dr Kyriacos Mouyis and Dr Sofia Metaxa, Frimley Health NHS Foundation Trust.

  • This is an updated version of an article that was first published in June 2014.

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  1. Habib G, Hoen B, Tornos P et al. Eur Heart J 2009 Oct; 30(19): 2369-413.
  2. Wang A. J Am Coll Cardiol 2012; 59(22): 1977-8.
  3. Dayer MJ, Jones S et all. Incidence of infective endocarditis in England, 2000-13. 2015 Mar; 28(385): 1219 -28.
  4. Habib G, Lancellotti P, et al :2015 ESC Guidelines for the management of infective endocarditis. Eur Heart J. 2015;hv319.0.1093/eurheartj/ehv319.
  5. NICE. Prophylaxis against infective endocarditis. CG64. London, NICE, March 2008.

Suggested further CPD activity

These further action points may allow you to earn more credits.

  • Organise an audit of patients in your practice who have IE or artificial valves and review their use of antibiotic prophylaxis.
  • Review NICE and ESC guidelines for updates on IE management.
  • Arrange a meeting with the consultant cardiologist and surgeon to discuss a protocol for referring patients with suspected IE.

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