Infective endocarditis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

suspected infective endocarditis

1st line – supportive care

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1st line –

supportive care

Use an airway, breathing, and circulation (ABC) approach to guide initial management.

Monitor controlled oxygen therapy. An upper SpO ₂ limit of 96% is reasonable when administering supplemental oxygen to most patients with acute illness who are not at risk of hypercapnia.

Evidence suggests that liberal use of supplemental oxygen (target SpO ₂ >96%) in acutely ill adults is associated with higher mortality than more conservative oxygen therapy.[92]
A lower target SpO ₂ of 88% to 92% is appropriate if the patient is at risk of hypercapnic respiratory failure.[93]

If the patient requires fluid resuscitation, check local protocols for specific recommendations on fluid choice. There is debate, based on conflicting evidence, on whether there is a benefit in using normal saline or balanced crystalloid in critically unwell patients.

Practical tip

Be aware that large volumes of normal saline as the sole fluid for resuscitation may lead to hyperchloraemic acidosis.

Also note that use of lactate-containing fluid in a patient with impaired liver metabolism may lead to a spuriously elevated lactate level, so results need to be interpreted with other markers of volume status.

Consider admission to the intensive care unit if the patient has:

Sepsis
Acute heart failure
Acute valvular dysfunction
Multi-organ failure
Undergone surgical intervention for IE.

Obtain blood cultures prior to starting antibiotic therapy; this is vital because one dose of an antibiotic often masks an underlying bacteraemia and delays appropriate therapy.

If the patient is unwell (e.g., with sepsis), do not delay empirical antibiotic therapy while waiting to take three sets of blood cultures.
When a microorganism has been identified, repeat the blood cultures after 48 to 72 hours to check the effectiveness of treatment.[6]

Think ' Could this be sepsis?' based on acute deterioration in a patient with suspected infective endocarditis.[55][56][57] See Sepsis in adults.

Use a systematic approach, alongside your clinical judgement, for assessment; urgently consult a senior clinical decision-maker (e.g., ST3 level doctor in the UK).[55][57][58][59]
Refer to local guidelines for the recommended approach at your institution for assessment and management of the patient with suspected sepsis.

More info: Sepsis

Think 'Could this be sepsis?' based on acute deterioration in an adult patient in whom there is clinical evidence or strong suspicion of infection.[55][56][57]

The patient may present with non-specific or non-localised symptoms (e.g., acutely unwell with a normal temperature) or there may be severe signs with evidence of multi-organ dysfunction and shock.[55][56][57]
Remember that sepsis represents the severe, life-threatening end of infection.[109]

Use a systematic approach (e.g., National Early Warning Score 2 [NEWS2]), alongside your clinical judgement, to assess the risk of deterioration due to sepsis.[55][56][58][60] Consult local guidelines for the recommended approach at your institution.

Arrange urgent review by a senior clinical decision-maker (e.g., ST3 level doctor in the UK) if you suspect sepsis:[57][59]

Within 30 minutes for a patient who is critically unwell (e.g., NEWS2 score of 7 or more, evidence of septic shock, or other significant clinical concerns)
- A patient is also at high risk of severe illness or death from sepsis if they have a NEWS2 score below 7 and a single parameter contributes 3 points to their NEWS2 score and a medical review has confirmed that they are at high risk.
Within 1 hour for a patient who is severely unwell (e.g., NEWS2 score of 5 or 6) or within 1 hour of any intervention for suspected sepsis (antibiotics/fluid resuscitation/oxygen) if there is no improvement in the patient’s condition.

Follow your local protocol for investigation and treatment of all patients with suspected sepsis, or those at risk. Start treatment promptly. Determine urgency of treatment according to likelihood of infection and severity of illness, or according to your local protocol.[59][60]

In the community and in custodial settings: refer for emergency medical care in hospital (usually by blue-light ambulance in the UK) any patient who is acutely unwell with a suspected infection and is:[57]

Deemed to be at high risk of deterioration due to organ dysfunction (as measured by risk stratification)
At risk of neutropenic sepsis.

See Sepsis in adults.

Refer any patient with suspected or confirmed IE for multidisciplinary evaluation. Ideally this will be within a specific endocarditis team, if available, including a cardiologist who is an accredited specialist in echocardiography (or a cardiologist and an additional accredited specialist in echocardiography who can be a cardiologist or clinical physiologist/scientist), a cardiac surgeon, an infectious disease or microbiology specialist, a neurologist, and a neurosurgeon.[6][89]

Decisions on anticoagulant and antiplatelet therapy should be made on an individual basis by the multidisciplinary endocarditis team, if available.[6]

Plus – empirical broad-spectrum antibiotic therapy

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Plus –

empirical broad-spectrum antibiotic therapy

Treatment recommended for ALL patients in selected patient group

Once blood cultures have been collected, promptly start broad-spectrum antibiotic therapy until sensitivities are known.[6]

If the patient is unwell (e.g., with sepsis), do not delay empirical antibiotic therapy while waiting to take three sets of blood cultures.

Check local guidance and seek advice from an infectious disease or microbiology specialist; recommended empirical regimens may differ between regions.[6][7][89][130]

The following factors should be taken into account when choosing the most appropriate empirical antibiotics:[6][7]

Whether the patient has received previous antibiotic therapy
Whether the infection involves a native or prosthetic valve
- If a prosthetic valve is involved, when the patient had surgery
Local epidemiology and knowledge of antibiotic-resistant and culture-negative pathogens
Where the infection was acquired (community, nosocomial, or non-nosocomial healthcare-associated).

Adjust antibiotic therapy accordingly once blood culture results are known (usually within 48 hours).[6] See Native valve: confirmed infective endocarditis and Prosthetic valve: confirmed infective endocarditis below.

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Urgently refer any patient with acute heart failure for emergency surgery if they have persistent pulmonary oedema or cardiogenic shock despite medical therapy.[6] Give intravenous diuretics to manage pulmonary oedema prior to the surgery. See Acute heart failure.

Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[20][89]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

ACUTE

native valve: confirmed infective endocarditis

oral streptococci and Streptococcus gallolyticus: penicillin-susceptible

1st line – beta-lactam ± gentamicin; vancomycin

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1st line –

beta-lactam ± gentamicin; vancomycin

Cure rates of >95% can be achieved in patients treated with parenteral penicillin or ceftriaxone for IE caused by penicillin-susceptible oral streptococci or Streptococcus gallolyticus.[6][7] Treatment consists of either beta-lactam (e.g., benzylpenicillin, amoxicillin, ceftriaxone) monotherapy for 4 weeks or a beta-lactam plus gentamicin for 2 weeks.[6][7]

The 2-week regimen is only recommended if the patient has non-complicated native valve endocarditis and normal renal function.
The 4-week regimen should be used if the patient is >65 years of age, or has renal or cranial nerve VIII impairment.[7]
Netilmicin is recommended as an alternative to gentamicin by the European Society of Cardiology; however, it is not available in the UK and some other European countries.[7]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

Vancomycin monotherapy for 4 weeks is recommended if the patient is unable to tolerate penicillin (e.g., type I hypersensitivity reaction).[6][7]

If the patient is receiving treatment with aminoglycosides, monitor renal and liver function, and for possible ototoxicity continuously (before, during, and after treatment). Also monitor serum aminoglycoside level during treatment.[7][114]

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

benzylpenicillin sodium: 7.2 to 14.4 g/day intravenously given in divided doses every 4 hours for 4 weeks

amoxicillin: 100-200 mg/kg/day intravenously given in divided doses every 4-6 hours for 4 weeks

ceftriaxone: 2 g intravenously/intramuscularly every 24 hours for 4 weeks

benzylpenicillin sodium: 7.2 to 14.4 g/day intravenously given in divided doses every 4 hours for 2 weeks

amoxicillin: 100-200 mg/kg/day intravenously given in divided doses every 4-6 hours for 2 weeks

ceftriaxone: 2 g intravenously/intramuscularly every 24 hours for 2 weeks

-- AND --

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Secondary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours for 4 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

oral streptococci and Streptococcus gallolyticus: increased exposure or resistant to penicillin

1st line – beta-lactam + gentamicin; vancomycin

Back

1st line –

beta-lactam + gentamicin; vancomycin

The incidence of streptococci with penicillin resistance is increasing.[6] If the patient has streptococcal endocarditis with increased antibiotic exposure or relative resistance to penicillin, a beta-lactam (e.g., benzylpenicillin, amoxicillin, ceftriaxone) for 4 weeks plus gentamicin for 2 weeks is the recommended regimen.[6]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

Vancomycin for 4 weeks is recommended if the patient is unable to tolerate penicillin (e.g., type I hypersensitivity reaction).[6]

Primary options

benzylpenicillin sodium: 7.2 to 14.4 g/day intravenously given in divided doses every 4 hours for 4 weeks

amoxicillin: 12 g/day intravenously given in divided doses every 4 hours for 4 weeks

ceftriaxone: 2 g intravenously/intramuscularly every 24 hours for 4 weeks

-- AND --

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Secondary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours for 4 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

methicillin-sensitive staphylococci

1st line – beta-lactam; daptomycin + ceftaroline or fosfomycin

Back

1st line –

beta-lactam; daptomycin + ceftaroline or fosfomycin

A beta-lactam (e.g., flucloxacillin, cefazolin) is the treatment of choice in oxacillin-susceptible strains.[7][110]

Cefazolin is recommended particularly if the patient has renal impairment[7][110]
Staphylococcal endocarditis is an increasingly recognised entity, due to high rates of hospital exposure and the development of resistant organisms.

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

Cefazolin, or daptomycin combined with ceftaroline or fosfomycin, is recommended if the patient has an oxacillin-resistant strain or is unable to tolerate penicillin (e.g., type I hypersensitivity reaction). The recommended treatment course is 4 to 6 weeks.[6][7]

Staphylococcus aureus is the most common cause of endocarditis in patients who use intravenous drugs.[3] If these patients have right-sided endocarditis, gentamicin has been shown to increase the rate of microbial killing when used in combination with a beta-lactam. However, aminoglycosides are no longer recommended in this scenario due to the increased risk of nephrotoxicity.[112][113]

Primary options

flucloxacillin: 12 g/day intravenously given in divided doses every 4-6 hours for 4-6 weeks

cefazolin: 6 g/day intravenously given in divided doses every 8 hours for 4-6 weeks

Secondary options

daptomycin: 10 mg/kg intravenously every 24 hours for 4-6 weeks

-- AND --

ceftaroline: 1800 mg/day intravenously given in divided doses every 8 hours for 4-6 weeks

fosfomycin: 8-12 g/day intravenously given in divided doses every 6 hours for 4-6 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

methicillin-resistant staphylococci

1st line – vancomycin; daptomycin + cloxacillin or ceftaroline or fosfomycin

Back

1st line –

vancomycin; daptomycin + cloxacillin or ceftaroline or fosfomycin

Vancomycin is the treatment of choice if the patient has methicillin-resistant staphylococcal endocarditis.[6] Daptomycin in combination with cloxacillin or ceftaroline or fosfomycin may be used if the patient has vancomycin resistance.[6][7]

There may be regional differences in treatment duration (e.g., 4-6 weeks).[6]

Primary options

vancomycin: 30-60 mg/kg/day intravenously given in divided doses every 8-12 hours for 4-6 weeks

Secondary options

daptomycin: 10 mg/kg intravenously every 24 hours for 4-6 weeks

-- AND --

cloxacillin: 12 g/day intravenously given in divided doses every 4 hours for 4-6 weeks

ceftaroline: 1800 mg/day intravenously given in divided doses every 8 hours for 4-6 weeks

fosfomycin: 8-12 g/day intravenously given in divided doses every 6 hours for 4-6 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

beta-lactam and gentamicin-susceptible enterococci

1st line – amoxicillin or ampicillin + ceftriaxone or gentamicin

Back

1st line –

amoxicillin or ampicillin + ceftriaxone or gentamicin

If the patient has a beta-lactam or gentamicin-susceptible strain of enterococci, they should be treated with a beta-lactam (e.g., amoxicillin, ampicillin) plus ceftriaxone for 6 weeks or gentamicin for 2 weeks.

The combination of ampicillin or amoxicillin plus ceftriaxone for 6 weeks may also be used if the patient has an Enterococcus faecalis strain with high-level aminoglycoside resistance, although this treatment is not active against Enterococcus faecium.[6][7]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

amoxicillin: 200 mg/kg/day intravenously given in divided doses every 4-6 hours for 6 weeks

ampicillin: 12 g/day intravenously given in divided doses every 4-6 hours for 6 weeks

-- AND --

ceftriaxone: 4 g/day intravenously given in divided doses every 12 hours for 6 weeks

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

beta-lactam resistant enterococci

1st line – vancomycin + gentamicin

Back

1st line –

vancomycin + gentamicin

If the patient has IE due to Enterococcus faecalis, these strains can produce an inducible beta-lactamase, although this is rare. The patient should be treated with vancomycin for 6 weeks and gentamicin for 2 weeks.[6]

The treatment of enterococcal endocarditis, similar to that of viridans group streptococci, is based on the sensitivities to penicillin. Enterococci, unlike the viridans group streptococci, are not usually killed by antibiotics, but merely inhibited.

If the patient is receiving treatment with aminoglycosides, monitor renal and liver function, and for possible ototoxicity continuously (before, during, and after treatment). Also monitor serum aminoglycoside level during treatment.[7][114]

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours for 6 weeks

and

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

vancomycin-resistant enterococci

1st line – daptomycin + beta-lactam or fosfomycin

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

multidrug-resistant enterococci

1st line – consultation with infectious disease or microbiology specialist

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

HACEK microorganisms

1st line – ceftriaxone; ampicillin + gentamicin; ciprofloxacin

Back

1st line –

ceftriaxone; ampicillin + gentamicin; ciprofloxacin

Ceftriaxone is standard treatment if the patient has Haemophilus, Aggregatibacter (formerly Actinobacillus), Cardiobacterium, Eikenella, and Kingella (HACEK) IE, and should be continued for 4 weeks in native valve endocarditis.[6]

HACEK strains are also susceptible to other third-generation cephalosporins.[6]
Ampicillin should not be used as first-line therapy for treatment of HACEK endocarditis because some HACEK-group bacilli produce beta-lactamases and are increasingly ampicillin-resistant.[6] However, if they do not produce beta-lactamase, ampicillin (for 4 weeks) plus gentamicin (for 2 weeks) is an option.[6]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

HACEK strains are also susceptible to fluoroquinolones (e.g., ciprofloxacin), which are recommended if the patient is unable to tolerate penicillin (e.g., type I hypersensitivity reaction).[6]

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Systemic fluoroquinolone antibiotics, such as ciprofloxacin, may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system (CNS) effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[117]

Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Primary options

ceftriaxone: 2 g intravenously/intramuscularly every 24 hours for 4 weeks

Secondary options

ampicillin: 12 g/day intravenously given in divided doses every 4-6 hours for 4 weeks

and

gentamicin: 3 mg/kg/day intravenously/intramuscularly given in divided doses every 8-12 hours for 2 weeks

ciprofloxacin: 400 mg intravenously every 8-12 hours for 4 weeks; 750 mg orally twice daily for 4 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

culture-negative microorganisms (non-HACEK)

1st line – consultation with infectious disease or microbiology specialist

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

fungal endocarditis

1st line – consultation with infectious disease or microbiology specialist

Back

1st line –

consultation with infectious disease or microbiology specialist

Seek early advice from an infectious disease or microbiology specialist if the patient has fungal IE.[6] Mortality is very high (>40% to 50%) .[6][118]

Be aware that fungal infections most frequently affect patients with prosthetic valves and those who are immunocompromised.[118]
Patients who use intravenous drugs are also at increased risk of fungal IE.[118]
The most common causative agents are Candida and Aspergillus.[118]

Treatment includes valve replacement and antifungal therapy.[6][118][119]

Early surgical intervention is essential to prevent complications of fungal endocarditis.[6][131]

prosthetic valve: confirmed infective endocarditis

oral streptococci and Streptococcus gallolyticus: penicillin-susceptible

1st line – beta-lactam; vancomycin

Back

1st line –

beta-lactam; vancomycin

Cure rates of >95% can be achieved in patients treated with parenteral penicillin or ceftriaxone for IE caused by penicillin-susceptible oral streptococci or Streptococcus gallolyticus.[6][7] Treatment consists of beta-lactam (e.g., benzylpenicillin, amoxicillin, ceftriaxone) monotherapy for 6 weeks.[6][7]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

Vancomycin monotherapy for 6 weeks is recommended if the patient is unable to tolerate penicillin (e.g., type I hypersensitivity reaction).[7]

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

benzylpenicillin sodium: 7.2 to 14.4 g/day intravenously given in divided doses every 4 hours for 6 weeks

amoxicillin: 100-200 mg/kg/day intravenously given in divided doses every 4-6 hours for 6 weeks

ceftriaxone: 2 g intravenously/intramuscularly every 24 hours for 6 weeks

Secondary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours for 6 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

oral streptococci and Streptococcus gallolyticus: increased exposure or resistant to penicillin

1st line – beta-lactam or vancomycin + gentamicin

Back

1st line –

beta-lactam or vancomycin + gentamicin

The incidence of streptococci with penicillin resistance is increasing.[6] If the patient has streptococcal endocarditis with increased antibiotic exposure or relative resistance to penicillin, a beta-lactam (e.g., benzylpenicillin, amoxicillin, ceftriaxone) for 6 weeks plus gentamicin for 2 weeks is the recommended regimen.[6]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

Vancomycin for 6 weeks and gentamicin for 2 weeks is recommended if the patient is unable to tolerate penicillin (e.g., type I hypersensitivity reaction).[7]

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

benzylpenicillin sodium: 7.2 to 14.4 g/day intravenously given in divided doses every 4 hours for 6 weeks

amoxicillin: 12 g/day intravenously given in divided doses every 4 hours for 6 weeks

ceftriaxone: 2 g intravenously/intramuscularly every 24 hours for 6 weeks

-- AND --

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Secondary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours for 6 weeks

and

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

methicillin-sensitive staphylococci

1st line – beta-lactam + rifampicin + gentamicin

Back

1st line –

beta-lactam + rifampicin + gentamicin

Combination therapy is recommended if the patient has IE caused by Staphylococcus aureus; infection is often rapidly progressive and carries a high mortality rate.[116]

If the patient has a methicillin-sensitive strain, treatment should include a beta-lactam (e.g., flucloxacillin or cefazolin) plus rifampicin for at least 6 weeks and gentamicin for 2 weeks.[6][7]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

If the patient is unable to tolerate penicillin (e.g., type I hypersensitivity reaction), cefazolin plus rifampicin (for at least 6 weeks) plus gentamicin (for 2 weeks) is recommended.[6][7]

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

flucloxacillin: 12 g/day intravenously given in divided doses every 4-6 hours for at least 6 weeks

cefazolin: 6 g/day intravenously given in divided doses every 8 hours for at least 6 weeks

-- AND --

rifampicin: 900 mg/day intravenously/orally given in divided doses every 8 hours for at least 6 weeks

-- AND --

gentamicin: 3 mg/kg/day intravenously/intramuscularly given in divided doses every 12-24 hours for 2 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

methicillin-resistant staphylococci

1st line – vancomycin + rifampicin + gentamicin

Back

1st line –

vancomycin + rifampicin + gentamicin

Vancomycin plus rifampicin for 6 weeks is recommended if the patient has IE due to a methicillin-resistant species. Gentamicin should be used during the first 2 weeks of therapy.[7]

Methicillin-resistant species are becoming more prevalent, especially in hospitalised patients.

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

vancomycin: 30-60 mg/kg/day intravenously given in divided doses every 8-12 hours for at least 6 weeks

and

rifampicin: 900-1200 mg/day intravenously/orally given in divided doses every 8-12 hours for at least 6 weeks

and

gentamicin: 3 mg/kg/day intravenously/intramuscularly given in divided doses every 12-24 hours for 2 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

beta-lactam and gentamicin-susceptible enterococci

1st line – amoxicillin or ampicillin + ceftriaxone or gentamicin

Back

1st line –

amoxicillin or ampicillin + ceftriaxone or gentamicin

If the patient has IE due to a penicillin- or gentamicin-susceptible strain of enterococci, they should be treated with a beta-lactam (e.g., amoxicillin, ampicillin) plus ceftriaxone for 6 weeks or gentamicin for 2 weeks.

The combination of ampicillin or amoxicillin plus ceftriaxone for 6 weeks may also be used if the patient has an Enterococcus faecalis strain with high-level aminoglycoside resistance, although it is not active against Enterococcus faecium.[6][7]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

amoxicillin: 200 mg/kg/day intravenously given in divided doses every 4-6 hours for 6 weeks

ampicillin: 12 g/day intravenously given in divided doses every 4-6 hours for 6 weeks

-- AND --

ceftriaxone: 4 g/day intravenously given in divided doses every 12 hours for 6 weeks

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

beta-lactam resistant enterococci

1st line – vancomycin + gentamicin

Back

1st line –

vancomycin + gentamicin

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Primary options

vancomycin: 30 mg/kg/day intravenously given in divided doses every 12 hours for 6 weeks

and

gentamicin: 3 mg/kg intravenously/intramuscularly every 24 hours for 2 weeks

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

vancomycin-resistant enterococci

1st line – daptomycin + beta-lactam or fosfomycin

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

multidrug-resistant enterococci

1st line – consultation with infectious disease or microbiology specialist

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

HACEK microorganisms

1st line – ceftriaxone; ampicillin + gentamicin; ciprofloxacin

Back

1st line –

ceftriaxone; ampicillin + gentamicin; ciprofloxacin

Ceftriaxone is standard treatment if the patient has Haemophilus, Aggregatibacter (formerly Actinobacillus), Cardiobacterium, Eikenella, and Kingella (HACEK) endocarditis, and should be continued for 6 weeks for prosthetic valve endocarditis.[6]

HACEK strains are also susceptible to other third-generation cephalosporins.[6]
Ampicillin should not be used as first-line therapy for treatment of HACEK endocarditis because some HACEK-group bacilli produce beta-lactamases and are increasingly ampicillin-resistant.[6] However, if they do not produce beta-lactamase, ampicillin (for 6 weeks) plus gentamicin (for 2 weeks) is an option.[6]

If the patient reports a penicillin allergy, determine the timing, extent, and nature of any previous reaction.[6]

In general, if the patient has a history of type I hypersensitivity anaphylactoid reactions or severe excoriating rashes, do not give penicillins or cephalosporins (10% to 15% cross-reactivity).
If the patient has a low-risk penicillin allergy, consider giving a single dose of a penicillin or cephalosporin while monitoring the patient closely.[121] A low-risk penicillin allergy includes:[121]
- Unknown reaction >10 years previously
- Type A adverse drug reaction (pharmacologically predictable intolerance) where direct de-labelling was not accepted by the patient
- History of an unspecified childhood rash, localised injection-site reaction (only), or maculopapular exanthem >10 years ago.

HACEK strains are also susceptible to fluoroquinolones (e.g., ciprofloxacin), which are recommended if the patient is unable to tolerate penicillin (e.g., type I hypersensitivity reaction).

The UK-based Medicines and Healthcare products Regulatory Agency has issued a drug safety alert about the increased risk of deafness associated with aminoglycoside treatment in patients with mitochondrial mutations.[114]
Follow your local protocols on genetic testing for mitochondrial mutations. Particularly consider mitochondrial mutation screening if the patient has a maternal history of deafness or mitochondrial mutations, or is having long-term or recurrent aminoglycoside treatment. Do not delay urgent antibiotic treatment for genetic testing.[114]

Systemic fluoroquinolone antibiotics, such as ciprofloxacin, may cause serious, disabling, and potentially long-lasting or irreversible adverse events. This includes, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and CNS effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[117]

Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability).
Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

Primary options

ceftriaxone: 2 g intravenously/intramuscularly every 24 hours for 6 weeks

Secondary options

ampicillin: 12 g/day intravenously given in divided doses every 4-6 hours for 6 weeks

and

gentamicin: 3 mg/kg/day intravenously/intramuscularly given in divided doses every 8-12 hours for 2 weeks

ciprofloxacin: 400 mg intravenously every 8-12 hours for 6 weeks; 750 mg orally twice daily for 4 weeks

Consider – surgery

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Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

culture-negative microorganisms (non-HACEK)

1st line – consultation with infectious disease or microbiology specialist

Consider – surgery

Back

Consider –

surgery

Additional treatment recommended for SOME patients in selected patient group

Many patients require surgery. Timing of surgical intervention should be decided by a multidisciplinary endocarditis team, if available.[6][20][89][125]

Indications for surgery include:[6][7][89][125]

Heart failure with:
- Cardiogenic shock or pulmonary oedema (requires emergency surgery), or
- Poor haemodynamic tolerance (requires urgent surgery)
Uncontrolled infection with:
- Local complications (e.g., abscess, false aneurysm, fistula, enlarging vegetation)
- Persistent positive blood cultures (despite appropriate antibiotic therapy for more than 1 week)
- Resistant bacteria or fungi
- Prosthetic valve endocarditis caused by Staphylococcus aureus or non-HACEK gram-negative bacilli
High risk of embolism or established embolism:
- Vegetation ≥10 mm and emboli despite appropriate antibiotic therapy
- Vegetation ≥10 mm and another reason for surgery (e.g., patients with significant valvular dysfunction, whether a direct result of endocarditis process or not)
- Vegetation ≥10 mm and no evidence of embolus.

Temporary cardiac pacing is recommended if the patient has atrioventricular block secondary to aortic root abscess.

The aims of surgery are to remove infected tissue completely and to repair or replace the affected valves, thus restoring cardiac anatomy.

fungal endocarditis

1st line – consultation with infectious disease or microbiology specialist

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1st line –

consultation with infectious disease or microbiology specialist

Seek early advice from an infectious disease or microbiology specialist if the patient has fungal IE.[6] Mortality is very high (>40% to 50%).[6][118]

Be aware that fungal infections most frequently affect patients with prosthetic valves and those who are immunocompromised.[118]
Patients who use intravenous drugs are also at increased risk of fungal IE.[118]
The most common causative agents are Candida and Aspergillus.[118]

Treatment includes valve replacement and antifungal therapy.[6][118][119]

Valve replacement surgery needs be performed as soon as possible in prosthetic valve Candida endocarditis.[132]

ONGOING

at high risk of infective endocarditis

1st line – advice ± antibiotic prophylaxis

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1st line –

advice ± antibiotic prophylaxis

Guidelines differ in their recommendations for antibiotic prophylaxis; check your local protocol. Decisions about antibiotic prophylaxis should only be made after careful evaluation of the individual patient’s circumstances, following discussion with the patient, taking into account the patient’s values and preferences, and using your clinical judgement.

The European Society of Cardiology (ESC) recommends that antibiotic prophylaxis should only be considered if the patient is at highest risk of IE and undergoing a dental procedure that requires manipulation of the gingival or periapical region of the teeth or perforation of the oral mucosa. The ESC considers a patient to be at highest risk of IE if they have:[6]

A prosthetic valve, including a transcatheter valve or a valve in which any prosthetic material was used for valve repair
A history of a previous episode of IE
Untreated cyanotic congenital heart disease or congenital heart disease that has been repaired with a prosthetic material (including valved conduits or systemic-to-pulmonary shunts)
A ventricular assist device.

In the UK, the National Institute for Health and Care Excellence (NICE) recommends that an at-risk patient undergoing interventional procedures should not be given antibiotic prophylaxis against IE routinely. However, NICE emphasises that antibiotic therapy is still necessary to treat active or potential infections.[36] NICE considers a patient to be at risk if they have:[36]

Acquired valvular heart disease with stenosis or regurgitation
Hypertrophic cardiomyopathy
Previous IE
Structural congenital heart disease, including surgically corrected or palliated structural conditions, but excluding isolated atrial septal defect, fully repaired ventricular septal defect, fully repaired patent ductus arteriosus, and closure devices that are judged to be endothelialised
Valve replacement.

NICE recommends giving clear information about prevention to any patient at risk of IE, which should include:[36]

The benefits and risks of antibiotic prophylaxis, and an explanation of why antibiotic prophylaxis is no longer routinely recommended
The importance of maintaining good oral health
Symptoms that may indicate IE and when to seek expert advice
The risks of undergoing invasive procedures, including non-medical procedures such as body piercing or tattooing.

The recommendations from the ESC and NICE may not be universally accepted in other countries.

The most common cause of infective endocarditis following dental, oral, respiratory tract, or oesophageal procedures is Streptococcus viridans (alpha-haemolytic streptococci). Therefore, antibiotics (if they are to be given for prophylaxis) are directed toward this organism, and administered as a single dose 30 to 60 minutes before the procedure.

Base your choice of antibiotic on your local hospital protocols.

The evidence for antibiotic prophylaxis preventing infection following dental procedures and instrumentation of the respiratory, genitourinary, or gastrointestinal tract is weak. Conflicting data suggest that a reduction in bacteraemia may not result in a lower incidence of infective endocarditis in low-risk individuals.[50] The risk of bacteraemia resulting from interventions such as dental procedures and instrumentation of the respiratory, genitourinary, or gastrointestinal tract is significantly smaller than from usual life-time activities such as toothbrushing or chewing.[51] Data have indicated that, even if treatment with prophylactic antibiotics were 100% effective, only a small number of cases would be prevented.

Primary options

amoxicillin: 2 g orally as a single dose 30-60 minutes before procedure

ampicillin: 2 g intravenously/intramuscularly as a single dose 30-60 minutes before procedure

Secondary options

cefalexin: 2 g orally as a single dose 30-60 minutes before procedure

ceftriaxone: 1 g intravenously/intramuscularly as a single dose 30-60 minutes before procedure

cefazolin: 1 g intravenously/intramuscularly as a single dose 30-60 minutes before procedure

azithromycin: 500 mg orally as a single dose 30-60 minutes before procedure

clarithromycin: 500 mg orally as a single dose 30-60 minutes before procedure

doxycycline: 100 mg orally as a single dose 30-60 minutes before procedure

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Infective endocarditis

Treatment algorithm

suspected infective endocarditis

supportive care

Practical tip

More info: Sepsis

empirical broad-spectrum antibiotic therapy

surgery

native valve: confirmed infective endocarditis

beta-lactam ± gentamicin; vancomycin

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

surgery

beta-lactam + gentamicin; vancomycin

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

surgery

beta-lactam; daptomycin + ceftaroline or fosfomycin

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

surgery

vancomycin; daptomycin + cloxacillin or ceftaroline or fosfomycin

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

Secondary options

surgery

amoxicillin or ampicillin + ceftriaxone or gentamicin

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

surgery

vancomycin + gentamicin

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

surgery

daptomycin + beta-lactam or fosfomycin

Primary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options

surgery

consultation with infectious disease or microbiology specialist

surgery

ceftriaxone; ampicillin + gentamicin; ciprofloxacin

Primary options

Secondary options

These drug options and doses relate to a patient with no comorbidities.

Primary options

Secondary options

Drug choice, dose and interactions may be affected by the patient's comorbidities. Check your local drug formulary.

Primary options