12th March 2024

Infective Endocarditis

Background

Infective endocarditis (IE) defines an infection involving the innermost lining of the heart- the endocardium. It includes infections affecting the cardiac valves, the chordae tendineae and the mural endocardium. The incidence of IE is rising and is estimated at 3-10 cases per 100,000 per year. Despite recent advancements relating to diagnosis and management of IE, prognosis remains poor, with an inpatient mortality of approximately 22%. Risk factors for IE include the following:

• Previous history of IE
• Presence of prosthetic heart valves
• Specific types of congenital heart disease
• Presence of cardiac devices or intravascular catheters
• History of intravenous drug use

Frequent aetiological agents involved in IE are listed below:

• Streptococci viridans
• Staphylococcus aureus
• Enterococci 
• Coagulase-negative staphylococci
• Brucella species
• Coxiella burnetii
• Culture-negative Haemophilus species, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens and Kingella species (HACEK group of organisms)

Clinical manifestations

The majority of patients will present with nonspecific symptoms, including fever, rigors, lethargy and weight loss. Other signs associated with IE include:

• A new or changing murmur: this can be found in up to 85% of patients
• Splinter haemorrhages: septic emboli from the heart valve become lodged in small capillaries and are visible beneath the nail bed
• Roth’s spots: pale lesions on the retina surrounded by a rim of haemorrhage usually diagnosed by fundoscopy. 
• Acute renal failure: occurs in up to 30% of patients and is an independent risk factor for inpatient mortality.
• Janeway lesions: non-tender haemorrhagic macules present over the soles and palms caused by septic microemboli.
• Osler’s nodes: tender nodules found on the tips of fingers and toes due to a local immunological response caused by immune complex deposition within the skin. 
• Embolic sequelae: due to the migration of septic thrombi from the heart. In left-sided IE, the brain and spleen are the most common site of embolism, whereas right-sided IE can lead to pulmonary emboli. Ischemic strokes are a common complication of cerebral emboli.

Diagnosis

Blood tests may show raised inflammatory markers (CRP and ESR) with leukocytosis. While these tests are not specific for IE, they can reflect the severity of IE-induced sepsis. Blood cultures are essential for identifying the organisms involved, and three sets of blood cultures from different venipuncture sites should be taken before initiating empirical antibiotic therapy. 

Transthoracic echocardiography (TTE) can look for evidence of IE in the form of valvular vegetations, abscess formation or prosthetic valve dehiscence. Due to the high virulence associated with Staphylococcus aureus, positive blood cultures with this organism is an indication for performing a TTE to exclude IE.

Where TTE is negative or inconclusive, but the suspicion for IE remains high, transoesophageal echocardiography  (TOE) offers superior views and is advised. The latter is also recommended in suspected cases of IE in patients with prosthetic valves. 

Other imaging for diagnosis of cardiac involvement includes 18F-FDG PET/CT and Cardiac CT.

Modified Duke’s Criteria

The modified Duke’s criteria uses echocardiographic findings, blood culture results and clinical signs to risk stratify the likelihood of IE. For diagnosis of IE, the following must be fulfilled:

• 2 major criteria OR
• 1 major and 3 minor criteria OR
• 5 minor criteria

Major criteria: Microbiological:

• Growth of typical IE organisms from two separate blood cultures (Streptococcus viridans, Strep. gallolyticus (formerly S . bovis), Staphylococcus aureus, HACEK group, Community-acquired enterococci
• Microorganisms typical for IE from persistently positive blood cultures (two positive blood cultures drawn 12h apart or all three or majority of four positive blood cultures with first and last samples drawn more than 1 hour apart)
• Single blood culture or serology positive for Coxiella burnetii

Major criteria: Imaging:

• TTE/TOE showing vegetations/abscess/pseudoaneurysm/intracardiac fistula/valve perforation/new dehiscence of prosthetic valve/
• 18F-FDG PET/CT showing abnormal activity around prosthetic valve implantation site (if valve was implanted more than three months ago)
• Paravalvular lesions on Cardiac CT 

Minor criteria:

• Risk factors for IE (IVDU, structural cardiac pathology)
• Fever 
• Immunological phenomena (Osler’s nodes, Roth’s spots, Glomerulonephritis)
• Vascular phenomena
• Positive blood cultures failing to meet major criteria.

Management

Native valve endocarditis is typically treated with antibiotic duration of 2-6 weeks. Prosthetic valve endocarditis requires treatment for longer than 6 weeks (see Table 1).

Table 1: Treatment and duration of antibiotics in IE. Adapted from 2015 ESC Guidelines for the management of infective endocarditis

Approximately half of patients with IE will eventually require surgery as a result of complications. Indications for cardiac surgery include:

• Heart Failure: aortic/mitral valve IE resulting in severe regurgitation with subsequent cardiogenic shock or pulmonary congestion. 
• Perivalvular extension: this can lead to formation of abscesses resulting in atrio-ventricular blocks and acute coronary syndromes.
• Resistant infection: fever and blood cultures remaining positive 7-10 days after antibiotic initiation
• Fungal aetiology: IE caused by these organisms have a low chance of being successfully treated with antibiotics alone
• Prevention of septic emboli: size of vegetations are associated with an increased risk of embolisation to the brain and lungs. Aortic or mitral vegetations >10mm on echocardiography are an indication for surgical escalation. 

As per the ESC 2018 update, antibiotic prophylaxis is currently recommended only for those patients with the highest risk of IE undergoing invasive dental operations. Those deemed to be at highest risk of I.E include one of three groups:

• Patients with a prosthetic valve or have had cardiac valve repair with prosthetic material
• Patients with previous IE
• Patients with untreated cyanotic heart disease

Antibiotics currently licensed for prophylaxis include either Amoxicillin or Ampicillin. Clindamycin can be used in cases of Penicillin allergy.

References

• 2015 ESC Guidelines for the Management of Infective Endocarditis. Available at https://academic.oup.com/eurheartj/article/36/44/3075/2293384 
• BMJ Best Practice Infective Endocarditis. Available at https://bestpractice.bmj.com/topics/en-gb/3000215
• Khan et al 2016. International Guideline Changes and the Incidence of Infective Endocarditis: a Systematic Review. Available at https://pubmed.ncbi.nlm.nih.gov/27621836/
• How to achieve IE prophylaxis 2018. Available at: https://www.escardio.org/Journals/E-Journal-of-Cardiology-Practice/Volume-16/vol16no33