Infective Endocarditis

Original Author: Adam Bonfield
Last Updated: 29th July 2018
Revisions: 12

Infective Endocarditis (IE) is an infectious disease of the heart and surrounding vessels.

It is most commonly seen in patients with a history of congenital or acquired cardiac disease, however an increasing number of cases are due to invasive instrumentation procedures and indwelling prosthetic material (1).

IV drug users have an increased incidence of IE however fortunately this is still rare in the paediatric population.

The most common underlying congenital heart disease conditions in which IE occurs are; ventricular septal defects, patent ductus arteriosus, aortic valve abnormalities including bicuspid aortic valve and tetralogy of fallot (1).

This can be pre- or post-repair but if post-repair, the presence of a residual defect increases the risk of IE (1).


Pathophysiology

In order for IE to occur you must have the triad of endothelial damage, platelet adhesion and microbial adherence (1).

In the case of structural abnormalities of the heart or great vessels, there is a significant pressure gradient with or without turbulent flow leading to the endothelial damage through sheer stress forces (1-2).

As for prosthetic material, they can also cause endothelial damage and promote a sterile platelet-fibrin deposition on this endothelium (1-2).

Once this has occurred, there needs to be a bacteraemia which can then adhere to this lesion and go on to invade underlying tissue. Once established and attached to the lesion, the bacteria are protected within the vegetation from phagocytic cells and host defense mechanisms and so can proliferate easily (1).


Microbiology

Organisms that cause IE have been seen to have specific surface receptors to fibronectin that allow the microbe to adhere to the thrombus at the outset (1).

Such organisms include Staphylococcus Aureus, Streptococcus Viridans, Streptococcus Pneumoniae, HACEK organisms (Haemophillus, Actinobacillus, Cardiobacterium, Eikenella and Kingella), Group A, C and G Streptococci and Candida albicans (1-2).

Certain organisms have been found to be associated after certain procedures. For example Alpha-haemolytic Streptococci (S. viridans) are most commonly found after dental procedures and Enterococci are commonly found after genitourinary or gastrointestinal surgery (2).


Clinical Features

Persistent low-grade fever, especially without another clear focus, is a concerning feature and should promote IE as a consideration. This is especially if there is a history of congenital heart disease, previous cardiac surgery or indwelling prosthetic material.

A heart murmur is almost always present formed either by turbulent flow around the vegetation or due to underlying heart disease. However, a change in the murmur is a concerning feature.

Splenomegally is a common finding and present in 70% of cases (2). Cutaneous manefestations are uncommon in paediatric population but can be present and include:

  • Petechiae – on skin and can be present on mucous membranes or conjunctival
  • Osler’s nodes – painful erythematous raised lesions on ends of fingers or toes
  • Janeway lesions – small, painless, erythematous, haemorrhagic raised lesions on palms or soles
  • Splinter haemorrhages – linear haemorrhagic streaks in the nail bed (2)

Splinter haemorrhages are one example of embolic phenomena that are seen in IE. Others include pulmonary emboli, haematuria due to glomerular nephritis, cerebral emboli causing seizures or hemiparesis, or roth spots which are retinal haemorrhages with pale centre often seen near optic disc (2).

However, it is important to remember that IE can present in a non-acute or sub-acute form. In these cases the clinical presentation can be subtle with non-specific symptoms including fatigue, malaise, weight loss, myalgia or possibly asymptomatic. Furthermore, they could present after a longer period of time with cardiac failure due to valvular destruction.


Investigations

The main investigations of choice for IE are blood cultures and Echocardiography (ECHO).

Positive blood cultures are present in 90% of IE cases (2). Multiple samples taken over the course of 48-72 hours from multiple sites are best in order to get a positive yield. It is also essential that an adequate volume of each sample is acquired to increase positive results.

Other blood results that suggest a diagnosis include anaemia, leukocytosis and raised ESR. Microscopic haematuria is also found in nearly a third of patients (2).

As for ECHO, the aims of examination include identifying vegetations and assessing the intracardiac damage done by these vegetations. It is however important to remember that both the absence of vegetations does not in itself rule out IE and conversely the presence of vegetations does not confirm it.

This is due to the possibility of small vegetations already having embolised causing a false negative result or normal anatomical variants, sterile thrombus or old treated thrombi leading to a false positive (2).

All investigations are used in conjunction with the Modified Duke’s Criteria for diagnosing IE. Table 1 shows that criterion that are used for this:

Major Criteria
Positive Blood culture for endocarditis Typical microorganism from 2 separate blood cultures – Viridans Streptococci, Streptococcus Bovis, HACEK group or community-acquired Staphylococcus Aureus or Enterococcus in absence of primary focus

OR

Microorganisms consistent with IE from persistent positive blood cultures – 2 positive cultures taken >12 hours apart OR all of 3 or a majority of 4 separate cultures of blood (with first and last drawn >1hr apart).

Evidence of endocardial involvement Positive ECHO findings – oscillating intra-cardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of anatomical explanation OR an abscess OR new partial dehiscence of prosthetic valve OR new valvular regurgitation
Minor Criteria
Predisposition Predisposing heart condition or IV drug use
Fever Temperatures >38.0 oC
Vascular Phenomena Major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial haemorrhage, conjunctival haemorrhages and Janeway lesions
Immunologic Phenomena Glomerulonephritis, Osler’s nodes, Roth spots, and rheumatoid factor
Microbiological Evidence Positive blood cultures but doesn’t meet major criteria or serological evidence of active infection with organism consistent with IE
ECHO findings Consistent with IE but doesn’t meet major criteria

Table 1: Dukes Criteria for diagnosis of Infective Endocarditis (3)

In order to confirm the diagnosis there should be two major criteria, one major and three minor criteria or five minor criteria (3). The diagnosis is suspected if 1 major and 1 minor criteria or 3 minor criteria present (4).

Finally the diagnosis can be rejected if there is firm alternative explanation explaining evidence of IE, there is resolution of IE syndrome with antibiotic therapy of <4 days course, there is no pathological evidence of IE at surgery or autopsy with antibiotics therapy of <4 days or does not meet other criteria (4).


Management

Once the diagnosis has been confirmed then the decision regarding management is either medical or surgical.

Whichever management option is chosen, the goal is to minimize complications such as systemic embolization, abscess formation, pseudoaneurysms, valvular perforation or heart failure (1).

The eventual decision of this will be made following discussion in a multi-disciplinary setting however table 2 suggests some factors that might increase the possible need for surgical intervention.

Vegetation Size >15mm for left sided lesions
Highly mobile vegetation
Persistent vegetation after systemic embolization
>1 embolic event in first 2 weeks of medical management
Increase in vegetation size despite medical management
Valvular Dysfunction Acute aortic or mitral insufficiency with signs of ventricular failure
Heart failure unresponsive to medical management
Valve perforation or rupture
Perivalvular extension Valvular dehiscence, rupture or fistula formation
New onset heart block
Large abscess or extension of abscess despite medical management

Table 2: ECHO findings that might suggest need for surgical intervention (4)

Even if surgical intervention is required, the patient will empirically started on IV antibiotics. The choice of antibiotics will eventually be determined by the sensitivities for the culture results, however consultation from the local Microbiology and Infectious Disease teams should be sought.

Below shows some guidance for antimicrobial therapy but is not an exhaustive list:

  • Aerobic cover is usually sufficient as IE caused by anaerobic bacteria is very rare
  • For highly sensitive streptococci, IV penicillin or IV ceftriaxone for 4 weeks should be sufficient. Alternatively a 2 week course of the above in combination with IV gentamicin may in some instances be sufficient.
  • For penicillin resistance streptococci, 4 weeks of IV penicillin or ceftriaxone for 4 weeks in combination with gentamicin for the first 2 weeks is required
  • For methicillin-susceptible staphylococci, a β-lactamase-resistant penicillin may be used for 6 weeks with or without gentamicin for the first 3-5 days
  • For methicillin-resistant however, vancomycin for 6 weeks with or without gentamicin for the first 3-5 days would be required
  • Enterococcus causes will need 4-6 weeks of IV penicillin in combination with gentamicin and if penicillin allergic would require 6 weeks of vancomycin and gentamicin
  • HACEK organisms require ceftriaxone along with gentamicin for 4 weeks
  • Fungal causes are best treated with amphotericin B
  • Any case with prosthetic valve in situ should receive a minimum of 6 weeks of appropriate antimicrobial therapy (2)

Prophylaxis

Previously it has been standard practice for healthcare professionals to give patients with congenital and acquired heart disease antibiotic prophylaxis for invasive procedures such as dental procedures or for some respiratory, gastrointestinal surgeries or cutaneous biopsies. However, this policy has now changed with the most recent NICE guidance (5).

It still agrees that patients who have acquired valve disease, previous IE, hypertrophic cardiomyopathy, valve replacement or structural congenital heart disease including surgically corrected conditions (excluding isolated ASDs, fully repaired VSDs, fully repaired PDAs and closure devices that are deemed to be endothelialised) are all at higher risk of developing IE.

However the advice is that it is not routinely recommended for antibiotic prophylaxis for those interventions previously covered including; dental procedures, upper and lower GI surgery, GU surgery, child birth and respiratory tract surgery (5).


Lightning Learning

Thanks to the team at www.em3.org.uk we now have a ‘Lightning Learning’ resource for you to take away.

References

(1) Lai W, Mertens L, Cohen M et al. Echocardiography in Pediatric and Congenital Heart Disease. Wiley Blackwell 2012.
(2) Park MK. The Pediatric Cardiology Handbook. 5th Philadelphia. Saunders 2016
(3) Durack DT, Lukes AS, Bright DK. New criteria for diagnosis of infective endocarditis: utilization of specific echocardiographic findings. Duke Endocarditis Service. American Journal of Medicine. 96(3):200-9, 1994
(4) Baddour LM, Wilson WR, Bayer AS et al. Infective endocarditis: diagnosis, antimicrobial therapy, and management of complications: a statement for healthcare professionals from the Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, and the Councils on Clinical Cardiology, Stroke, and Cardiovascular Surgery and Anesthesia, American Heart Association: endorsed by the Infectious Diseases Society of America. Circulation. 2005 Jun 14;111(23):e394-434.
(5) Prophylaxis against infective endocarditis: antimicrobial prophylaxis against infective endocarditis in adults and children undergoing interventional procedures. NICE Clinical guideline [CG64] Published date: March 2008 Last updated: July 2016

Author:

Dr Chris Oakley (Paediatric cardiology registrar)

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