Infective Endocarditis

Infective endocarditis is infection of the endocardial surface of the heart, most commonly affecting the heart valves. It arises from bacteraemia seeding a site of endothelial damage or an abnormal valve surface. It carries substantial morbidity and mortality if diagnosis or treatment is delayed, given the potential for valve destruction, embolic complications and progressive heart failure.

Native valve, prosthetic valve and intravenous drug use associated disease are distinct clinical categories. They differ in typical causative organisms and management considerations.

Pathophysiology and risk factors

Transient bacteraemia arises from a variety of sources, including dental procedures, skin infection, intravascular device related infection, or intravenous drug use. It seeds a nidus of platelet fibrin deposition at a site of pre-existing endothelial or valvular abnormality (degenerative valve disease, congenital heart disease, prosthetic material, or previous endocarditis).

Subsequent bacterial proliferation forms the characteristic vegetation. The vegetation drives progressive local valve destruction and serves as a source of septic embolisation to distant sites.

Fever, often prolonged and associated with constitutional symptoms (malaise, weight loss, night sweats), together with a new or changing cardiac murmur, forms the core clinical presentation.

Onset can be insidious over weeks in subacute disease, classically associated with lower virulence organisms such as viridans group streptococci. It can be more acute and fulminant in disease caused by more virulent organisms such as Staphylococcus aureus.

Peripheral stigmata are present in only a minority of modern presentations, given generally earlier diagnosis. They include:

• splinter haemorrhages
• Janeway lesions (painless erythematous macules on the palms and soles, reflecting septic embolisation)
• Osler nodes (painful nodules on the finger and toe pads, reflecting immune complex deposition)
• Roth spots on fundoscopic examination
• splenomegaly in more prolonged, subacute disease

Embolic complications reflect fragmentation and distal embolisation of vegetation material. They can affect any organ system. They are important and sometimes presenting manifestations of the underlying endocardial infection:

• stroke (from left sided vegetations)
• splenic and renal infarction
• in right sided disease (particularly associated with intravenous drug use), septic pulmonary emboli producing multiple cavitating lung lesions

New or progressive heart failure reflects valve destruction with resulting regurgitation. New conduction abnormality reflects extension of infection into the conducting system, particularly with aortic valve involvement and perivalvular abscess formation.

Both are serious complications indicating significant local disease progression and often prompt urgent surgical consideration.

Blood cultures are the essential diagnostic investigation. Take a minimum of three sets from separate venepuncture sites before antibiotic administration wherever the clinical situation permits. Persistently positive cultures for a typical endocarditis causing organism are a major diagnostic criterion.

Culture negative endocarditis occurs in a meaningful minority. It often reflects prior antibiotic exposure or a fastidious organism requiring specialised culture techniques or serological testing. It requires broader investigation, including serology for organisms such as Coxiella burnetii and Bartonella species where clinically relevant.

Echocardiography is essential for every suspected case. Transthoracic echocardiography is the initial investigation. Transoesophageal echocardiography offers substantially superior sensitivity, particularly for prosthetic valves, smaller vegetations and perivalvular complications (abscess formation).

Pursue transoesophageal echocardiography where transthoracic imaging is negative or equivocal but clinical suspicion remains significant, or where prosthetic valve involvement is suspected.

Diagnosis is established using the modified Duke criteria.

• Major criteria: positive blood cultures with a typical organism or persistently positive cultures, and echocardiographic evidence of endocardial involvement.
• Minor criteria: predisposing cardiac condition or intravenous drug use, fever, vascular phenomena, immunological phenomena, and microbiological evidence not meeting major criteria.
• Definite endocarditis is diagnosed with two major criteria, one major and three minor criteria, or five minor criteria.

Further investigation is directed by the specific clinical presentation and suspected complications. It includes computed tomography or magnetic resonance imaging for suspected embolic complications (particularly cerebral imaging where neurological symptoms are present), and dental assessment given the frequent relevance of an oral source.

Start empirical antibiotic therapy after blood cultures have been obtained in a patient with a strong clinical suspicion of endocarditis. This applies particularly with haemodynamic instability or evidence of significant complications precluding a delay for culture results.

The regimen typically combines cover for staphylococci, streptococci and enterococci. For native valve disease, use vancomycin (loaded then dosed to a target trough of 15 to 20 mg per litre) combined with gentamicin 1 mg per kg intravenously every 8 hours. Gentamicin is used at this low dose specifically for synergistic rather than bactericidal effect against certain organisms, with close renal function and level monitoring.

For prosthetic valve disease or where healthcare associated infection is suspected, broaden the empirical regimen to include rifampicin 300 to 450 mg orally twice daily in addition to vancomycin and gentamicin. Staphylococcal infection, including coagulase negative staphylococci, is more likely in this population. Rifampicin provides important additional activity against organisms within biofilm on prosthetic material.

Once a specific causative organism and its susceptibility pattern are identified, narrow and tailor therapy accordingly:

• Penicillin sensitive viridans group streptococci: benzylpenicillin 1.2 to 2.4 g intravenously every 4 hours (or ceftriaxone 2 g intravenously once daily as a more convenient alternative) for 4 weeks.
• Methicillin sensitive Staphylococcus aureus native valve endocarditis: flucloxacillin 2 g intravenously every 4 to 6 hours for 4 to 6 weeks.
• Enterococcal endocarditis: ampicillin 2 g intravenously every 4 hours with either gentamicin or ceftriaxone, for a typical duration of 4 to 6 weeks depending on the specific clinical scenario.

Methicillin resistant Staphylococcus aureus endocarditis is treated with vancomycin (dosed to target trough) or daptomycin 8 to 10 mg per kg intravenously once daily, for a minimum of 6 weeks. Daptomycin is increasingly preferred given evidence of superior outcomes in bacteraemia and endocarditis. The higher dose end of this range is generally used for endocarditis, given the more severe nature of this infection compared with simpler bacteraemia.

Prosthetic valve endocarditis generally requires a minimum of 6 weeks of therapy, longer than the corresponding native valve regimen. This reflects the greater difficulty achieving adequate antibiotic penetration and clearance from infected prosthetic material and any associated biofilm.

Surgical intervention is indicated for:

• heart failure due to significant valve dysfunction
• uncontrolled infection despite appropriate antibiotic therapy (persistent bacteraemia, perivalvular abscess, fistula formation)
• prevention of embolism in patients with large vegetations (generally over 10 mm), particularly with a prior embolic event or in high risk locations such as the mitral valve

The decision regarding timing and necessity of surgery is made through multidisciplinary discussion involving cardiology, cardiac surgery and infectious disease specialists, given the complex balance of risks involved.

Antibiotic prophylaxis before dental and other invasive procedures is now recommended only for a restricted group of patients at highest risk of adverse outcome from endocarditis. These are those with a prosthetic valve or prosthetic material used for valve repair, previous infective endocarditis, and certain forms of congenital heart disease.

This is a substantial narrowing of prophylaxis recommendations compared with historical practice. There is limited evidence that prophylaxis prevents the large majority of endocarditis cases, which arise from incidental daily bacteraemia rather than specific identifiable procedures.

Where prophylaxis remains indicated in this high risk group, the standard regimen is amoxicillin 2 g orally as a single dose one hour before the procedure.