Overview

Infective endocarditis (IE) is the infection of the endocardium in the heart. It is a rare and life-threatening disease that has long-lasting effects on patients even after they have survived and been treated. As it presents non-specifically, it is easily overlooked or misdiagnosed. IE can be rapidly fatal if left untreated.

IE can have lesions known as vegetations. These are deposits of microorganisms, platelets, and inflammatory cells. These vegetations can detach and travel in the blood leading to embolic phenomena such as stroke.

In general, the mitral valve is most commonly affected. In intravenous drug users (IVDUs), the tricuspid valve is more commonly affected.

Epidemiology

  • Increased prevalence in patients with indwelling cardiac catheters
  • In the developed world, Staphylococcus aureus is the most common cause
  • In developing countries, viridans streptococci predominate
    • The most common viridans streptococci in IE are Streptococcus mitis and Streptococcus sanguinis
      • Streptococcus viridans is an umbrella term for these two species
  • Three times more common in men
  • Prevalence increases with age
  • Prevalence increases with other diseases e.g. diabetes, cancer, chronic alcohol consumption

Causes

  • Staphylococcus aureus is the most common cause in developed countries and IVDUs
  • Streptococcus viridans (Streptococcus mitis and Streptococcus sanguinis) are the most common in developing countries and in patients with poor dental hygiene following a dental procedure
  • Staphylococcus epidermidis and other coagulase-negative Staphylococci are a common cause in indwelling lines or prosthetic valves in the first 2 months
    •  After 2 months, Staphylococcus aureus predominates
  • HACEK species – Haemophilus, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens, and Kingella species

Risk Factors

  • Previous infective endocarditis
  • Valvular heart disease
  • Valve replacements
  • Structural congenital heart disease, even if it has been corrected
  • Hypertrophic cardiomyopathy
  • Intravenous drug use
  • Invasive vascular procedures e.g. haemodialysis

Presentation

Always have a low threshold when suspecting infective endocarditis. It should be suspected in any patient with:

  • Fever and signs and symptoms of embolism
  • Fever and heart failure with risk factors for IE
  • Fever and a new/worsening murmur – this is rare

Some features patients may have are:

Signs on Examination

  • Fever
  • Heart murmurs
  • Petechiae in the conjunctiva, on the chest or abdominal wall, dorsum of the hands and feet, or in the oral mucosa and soft palate
  • Splinter haemorrhages
  • Osler’s nodes
  • Clubbing – usually if long-standing
  • Roth’s spots – retinal haemorrhages with pale centres
  • Janeway’s lesions – usually with Staphylococcus aureus IE
  • Meningism

Differential Diagnoses

Rheumatic fever

  • Presentation may be very similar
  • Evidence of preceding streptococcal infection present
  • Positive antistreptolysin O antibodies or anti-DNAase B
  • Erythema marginatum, chorea, and polyarthritis are present in rheumatic fever

Investigations

All patients

  • Blood cultures:
    • If the patient is septic, do not delay giving empirical antibiotics
    • If possible, take 3 blood cultures at different venepuncture sites at 30-minute intervals before giving empirical antibiotics
  • Echocardiography:
    • May show valvular, mobile vegetations
  • Full blood count (FBC):
  • C-reactive protein (CRP):
    • A non-specific marker of inflammation, may be elevated
    • Useful for monitoring treatment
  • Urea and electrolytes (U&Es):
    • As a baseline
    • Urea may be elevated
  • Urinalysis:
    • To look for the distal spread of IE
    • May show haematuria, RBC casts, white cell casts, proteinuria, pyuria
  • ECG:
    • Progression of IE may lead to conduction abnormalities
    • May cause PR prolongation or AV node blocks
  • Echocardiography – a key investigation:
    • May show vegetations

Diagnosis

Modified Duke criteria

The modified Duke criteria are used to diagnose infective endocarditis. IE is diagnosed if any of the following are met:

  • A pathological criterion is positive
  • 2 major criteria
  • 1 major and 3 minor criteria
  • 5 minor criteria

Pathological criteria:

  • Microorganisms demonstrated by culture or on histological examination of valve tissue, vegetation, a vegetation that has embolised, or an intracardiac abscess sample

Major criteria:

  • Positive blood cultures for IE:
    • Typical IE microorganisms from 2 separate blood cultures
    • Typical microorganisms from persistently positive blood cultures which may either be:
      • ≥2 positive blood cultures drawn >12 hours apart or
      • All of 3 or a majority of ≥4 separate blood cultures with the first and last drawn ≥1 hour apart
    • Positive serology for Coxiella burnetii, Chlamydia psittaci, or Bartonella species
    • Positive molecular assays
  • Evidence of endocardial involvement:
    • Positive echocardiography findings (vegetations, abscesses, pseudoaneurysm, valvular perforation or aneurysm, new partial dehiscence of prosthetic valve)
    • New valvular regurgitation

Minor criteria:

  • Predisposing heart condition of IVDU
  • Fever over 38°C
  • Vascular phenomena:
  • Immune phenomena:
  • Microbiology:
    • Positive blood cultures that do not meet major criteria
    • Identification of previous recent embolic events or infectious aneurysms by imaging

Management

Initial “blind” therapy

  • Native valve endocarditis: amoxicillin (or ampicillin) + consider low-dose gentamicin
    • If penicillin allergic/suspected MRSA/severe sepsis: vancomycin + low-dose gentamycin
  • Prosthetic valve endocarditis: vancomycin + rifampicin + low-dose gentamicin

Native valve endocarditis due to Staphylococcus

  • Flucloxacillin
  • If penicillin allergic/MRSA: vancomycin + rifampicin

Prosthetic valve endocarditis due to Staphylococcus

  • Flucloxacillin + rifampicin + low-dose gentamicin
  • If penicillin allergic/MRSA: vancomycin + rifampicin + low-dose gentamicin

Endocarditis caused by fully-sensitive Streptococcus

  • Benzylpenicillin
  • If penicillin allergic: vancomycin (or teicoplanin) + low-dose gentamicin

Endocarditis caused by less-sensitive Streptococci

  • Benzylpenicillin + low-dose gentamicin
  • If penicillin-allergic or highly penicillin-resistant: vancomycin (or teicoplanin) + low-dose gentamicin

Endocarditis caused by enterococci

  • Amoxicillin (or ampicillin) + low-dose gentamicin or
  • Benzylpenicillin + low-dose gentamicin
  • If penicillin-allergic or penicillin-resistant: vancomycin (or teicoplanin) + low-dose gentamicin
  • If gentamicin resistant: amoxicillin (or ampicillin) + streptomycin

Endocarditis caused by HACEK organisms

  • Amoxicillin (or ampicillin) + low-dose gentamicin
  • If amoxicillin-resistant: ceftriaxone (or cefotaxime) + low-dose gentamicin

Surgery

Surgery is indicated if:

  • Heart failure develops
  • There is severe valvular dysfunction
  • There is an uncontrolled infection which may be characterised by:
    • Abscess formation
    • Enlarging vegetation
    • Prosthetic valve endocarditis due to Staphylococcus or non-HACEK gram-negative bacteria
    • Fungal or multidrug-resistant organism endocarditis
  • Recurrent embolic events e.g. stroke

Monitoring

  • After finishing antibiotics, patients should have transthoracic echocardiography to establish a new baseline
  • All patients should have blood cultures done at 1 and 2 weeks after treatment to ensure bacteraemia has subsided

Patient Advice

NICE does not recommend routine prescriptions of antibiotics in at-risk patients undergoing interventional procedures. Patients should:

  • Be educated on the benefits and risks of antibiotic prophylaxis and why antibiotic prophylaxis is no longer routinely recommended
  • Be educated on the importance of maintaining good oral health
  • Be safety-netted on the symptoms of IE and when to seek medical help
  • The risks of undergoing procedures, non-medical ones included such as body-piercing or tattoos

Complications

  • Acute heart failure
  • Embolic events e.g. stroke
  • Acute kidney injury
  • Valvular dehiscence, rupture, or fistula
  • Splenic abscess

Prognosis

  • Overall 1-year mortality is 30%
  • Factors associated with a worse prognosis are:
    • Patient:
      • Older age
      • Prosthetic valve IE
      • Diabetes mellitus
      • Comorbidities such as frailty, immunosuppression, etc.
    • Complications developing:
    • Microbiology:
      • Staphylococcus aureus
      • Non-HACEK gram-negative bacilli
    • Echocardiography:

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