L09 I&I Infective endocarditis

Lecture objectives

• discuss the significance of bacteraemia and sepsis in and role in IE
  • Bloiod culture as a diagnositc tool
• Discuss aetiology and pathogenesis
• outline risk factors associated with IE
• DIscuss lab diagnosis and treatment
• Rheumatic fever (RF), Rheumatic heart disease (RHD) and IE

Bacteraemia and septicaemia

Bacteraemia

• bacteria in blood
  • trauma to mucosa
  • transient
  • can cause disease in suscep Septicaemica
• pathological response to baceraemia
  • intravascular inflammatory response - unregulatio, generalised
    • proinflammatory
      • vasodilarion DIC thrombosis embolism ischaemia, haemorrhage necrosis hypoperfusion organ failure → death
• poorly defined clinically
  • sepsis is preferred term

Blood cultures

Your blood is generally sterile so anything within is potentially significant. Pyrexia of Unknown Origin (PUO) is generally the most common readon samples are taken. To ensure accuracy try to take these blood cultures before empiric therapy.

IF culture shows skin microbiome it could either be infection or contamination. this is a good example of why you need to take alot of samples. 3-4 sets over 24 hrs ideally at different sites. If seriously ill then 3 set over 1 hour. It can take days for a result to show so initial therapy must be empiric.

Background on Infective endocarditis

Infection of the endocardium, characterised by vegetations which are thrombus and microbes. These can embolise. Both native and artificial valves are susceptible. They can either be acute or subacute.

Acute (Short infections)

This is a rapid (days to weeks) infection. This can affect normal valve i.e no previous damage necessary. This is often caused by very virulent pathogens (often Staph. Aureus), and therefore you see necrosis, ulcers, and destruction of the valve. It does not respond well to antimicrobials, possibly prompting surgery to repair or replace the valve, and there is significant mortality involved, even if treated appropriately.

Subacute (Long infections)

A slow and insidious infection (wks to mths). These require previously damaged heart valves (think RHD/RF) as the organism which cause this are lower virulence organisms which could not colonise without a susceptible host. These respond to antimicrobials well. They tend to grow on fibrin depositions on damaged endothelium (I think… recheck)

Pathogenic aetiology of Infective endocarditis

Bacteria are the most common cause of IE, and gram positive cocci are responsible for >80% of infections.

Most common

S. aureus

This is the most common cause of acute IE, it can infect prosthetic and native vavles.

S. epidermidis

THis bacteria loves putting down biofilms especially in artificatial devices

Streptococci (Viridians strep)

This is a low virulence organism which resides in the oral microbiome. This is the most common cause of subacute IE.

Enterococci

Relevant in hospital acquired IE, GI/GU (gastro-urinary) procedures. Likes prosthetic valves

Less common…

HACEK group

Low virulence gram negative oropharyngeal microbiome microbes fastidious organisms so could be found in culture negative IE?

Gram negatives

E coli and pseudamonas Injecting drug users and immunocompromised mostly effected.

Fungi (Candida albicans)

ICU, IDU, prosthetic valves mostly effected.

Risks

Age: over 60 Sex: males more than females Heart or valvular disease Prosthetic device anything that can result in a bacteraemia Immunocompromised

Pathogenesis

Bacteria/platelet interaction

Bacteria/platelet interaction is the essential for the pathogenesis of IE (esp subacute IE). The interaction can be split into 3 parts:

1. Adhesion
   • This is where the bacteria initially binds to the platelet which activates the platelet
2. Activation
   • once the platelet is activated it does stuff like fibrin binding and upregulation of binding proteins
   • this leads to binding to more bacteria and platelets
3. Aggregation
   • More platelets and bacteria joint in to make the infective vegetation.

Subacute IE pathogeneis

Preexisting valve damage (ie with collagen exposed) triggers platelets and fibrin to bind and create a sterile vegetation which can be infected by a bacteraemia (the bacteria will adhere and lead to aggregation.) Additionally the abscess will protect central bacterial from immune response, antimicrobials etc.

Acute IE pathogenesis

The pathogenesis of this is much different when compared to subacute IE. This is caused by a virulent bacteria that needs no preexisting damage. Staph. aureus has special virulence factors such as adhesins and toxins/enzymes which allow it to bind directly to the valve and then just directly cause cell death and inflammation. rapid clinical course

Other notes

Where is the heart does IE occur most often?

Heart valves more likely and the left sided at that. This could be due to a few factors including but not limited to: high pressures causing more damage and therefore more sites affected, higher environmental oxygenation

When we do see right sided vegetations this is often due to IDUs and we see the tricuspid valve more frequently effected compared to the pulmonary.

Link to complications

The infected vegetation will be a source of bacteraemia (metastatic infection and sepsis), source of septic emboli (septic infarction), and immune complexes can clog up glomeruli.

This links to the clinical consequences bit

Device associated IE (mainly S. epidermidis)

This is a biofilm infection. As the device is foreign the body puts down lots of fibrin and platelets which are able to easily be colonised.

Clinical relevance

Clinical signs

• Fever (PUO) is the most common sign but in subacute IE, the elderly, or debilitated, fever is intermittent, low grade or absent.
• Heart murmur is often a good sign especially when its really recent and or changing. Often it is not initally detected (which is a good reason to perform checks on your patient often)
• Non-specific (not always present)
  • Chills, malaise,
  • anorexia, weightl oss,
  • myalgia, arthralgia,
  • dyspnea, cough,
  • abdominal pain nausea, vomiting
  • Elevated ESR/CRP/RF
• And additionally there where traditional signs that are not seen often anymore
  • Janeway lesions
  • oslers nodes
  • roth spots
  • splinter haemorrhages

Complications (these may be the presenting complaint)

• Cardiac: CHF, valvular insufficiency, MI, ring abscesses (collections of abscesses around the valve)
• Neurological: Embolic stroke intracerebral haemorrhage, abscesses
• Septic emboli: Kidneys, spleen, liver, lungs, skin, and gut
• Infection: Metastatic: osteomyelitis, septic arthritis, sepsis
• Glomerulonephritis: Renal failure
• Pulmonary: Embolism, abscesses, pneumothorax, effusion, empyema

Diagnosis of IE

Diagnosis depends on the Duke criteria, which is similar to the Jones criteria for RF. As infective endocarditis is a disease with diverse presentation a number of factors together lead to a diagnosis

Modified duke criteria

For a positive diagnosis you need: 2 major criteria OR 1 major and 3 minor OR 5 minor.

Major criteria include:

• 2 blood cultures positive for the common culprits
• Echocardiogram positive for IE, abscess, new partial dehiscense of artificial valve (valve is coming off attachment site), or new murmur.

Minor criteria

• Predisposing heart condition of injecting drug use
• fever
• vascular phenomena (septic emboli etc)
• immunologic phenomena (glomerulonephritits etc)
• microbiological evidence (Positive blood culture but without meeting a major criterion)

Treatment

Acute IE

This is a rapid disease so treatment is initially empiric. Do try to get a good blood culture though first. The likely cause is S. aureus so treat for that. take a clinical history, risks and a physical exam though.

Subacute IE

wait for blood culture results before treatment.

IE is a biofilm infection.

This is a difficult to treat infection. the treatment will be 2-6 wks and high dose bactericidal IV therapy is needed.

Antibacterial therapy

Staphs

for:

• native valve use Flucloxacillin
• prosthetic valve use flucloxacillin and maybe rifampacin or gentamicin
• Methicillin resistant (usually epidermidis but could be MRSA) use vancomycin

Streps

• penicillin and maybe gentamicin

Surgery

Surgery may be needed to replace a damaged valve especially in acute IE or presence of a prothetic valve or fungal IE.

An aside on RF

He just yaps about RF