INFECTIVE ENDOCARDITIS

an update
Dr.T.V.Rao MD

21-06-2013

Dr.T.V.Rao MD

Beginning of Knowledge on

Endocarditis
Knowledge about the origins of endocarditis stems from the work of Fernel in the early 1500s, and yet this infection still presents physicians with major diagnostic and management dilemmas.
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Definition of Infective Endocarditis

Infective endocarditis, a serious infection of the endocardium of the heart, particularly the heart valves, is associated with a high degree of illness and death. It generally occurs in patients with altered and abnormal heart architecture, in combination with exposure to bacteria through trauma and other potentially high-risk activities involving transient bacteraemia.
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Definition
Infective Endocarditis (IE): an infection of the hearts endocardial surface

Main Classification:
Native Valve IE Prosthetic Valve IE

Additional Consideration
Intravenous drug abuse (IVDA) IE Nosocomial IE
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Infective Endocarditis
Febrile illness Persistent bacteremia Characteristic lesion of microbial infection of the endothelial surface of the heart The vegetation
Variable in size Amorphous mass of fibrin & platelets Abundant organisms Few inflammatory cells
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Bacterial Endocarditis

Predisposing Factors
1. 2. 3. 4. 4. Dental manipulation Dental disease (caries, abscess) Extra cardiac infection (lung, urinary tract, skin, bone, abscess) Instrumentation (urinary tract, GI tract, IV infusions) 5. Cardiac surgery 6. Injection drug use 7. None apparent
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Infective Endocarditis
Acute
Toxic presentation Progressive valve destruction & metastatic infection developing in days to weeks Most commonly caused by S. aureus

Sub acute
Mild toxicity Presentation over weeks to months Rarely leads to metastatic infection Most commonly S. viridans or enterococcus

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Infective Endocarditis
Adult population
Rheumatic Heart Disease
20 25% of cases of IE in 1970s & 80s 7 18% of cases in recent reported series Mitral site more common in women Aortic site more common in men

Congenital Heart Disease

10 20% of cases in young adults 8% of cases in older adults PDA, VSD, bicuspid aortic valve (esp. in men>60)
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Infective Endocarditis
Intravenous Drug Abuse
Risk is 2 5% per pt./year Tendency to involve right-sided valves
Distribution in clinical series
46 78% tricuspid 24 32% mitral 8 19% aortic

Underlying valve normal in 75 93% S. aureus predominant organism (>50%, 60-70% of tricuspid cases)
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Causes of Bacteraemia
Brushing teeth Eating/chewing Dental work IV lines (colonised/infected) IV drug use Infected site/abscess
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alpha-haemolytic streptococci from oral flora

Staphylococcus aureus from skin/nose

Strep. pneumoniae, S.aureus

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Infecting Organisms
Common bacteria
Alpha haem streptococci (viridans S. mitis, S. sanguis) SUBACUTE Enterococci (E. faecalis) SUBACUTE Coagulase Negative Staphylococci PROSTHETIC VALVES, SUBACUTE

Less common bacteria

S. aureus ACUTE B-Haemolytic streptococci ACUTE Streptococcus pneumonia

Not so common
Fungi Pseudomonas / Coliforms HACEK group organisms

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Bacterial Pathogens

HACEK Group
Haemophilus spp. Actinobacillus actinomycetemcomitans Cardiobacterium hominis Eikenella corrodens Kingella kingae
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Infecting Organisms
Streptococci 60-80%
Alpha-haemolytic Streptococci (viridans S. mitis, S. oralis) 30-40% (subacute) Enterococci (E. faecalis) 5-18% (subacute) Beta-haemolytic streptococci (e.g. Gp A Strep) rare (acute)

Staphylococci 20-35%
S. aureus 10-27% (acute) Coagulase negative staphylococci (Staph epidermidis) 1-3 % (mainly prosthetic valve risk, subacute)

Fungi
Candida IVDU at risk (usually indolent) Aspergillus rare

Gram-negative bacteria rare Culture-negative endocarditis HACEK, Q-fever cases do occur, subacute

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Infective Endocarditis
Prosthetic Valve Endocarditis (PVE)
10 30% of all cases in developed nations Cumulative incidence
1.4 3.1% at 12 months 3.2 5.7% at 5 years

Early PVE within 60 days

Nosocomial (s. epi predominates)

Late PVE after 60 days

Community (same organisms as NVE)
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Infective Endocarditis
Pathology
NVE infection is largely confined to leaflets PVE infection commonly extends beyond valve ring into annulus/periannular tissue
Ring abscesses Septal abscesses Fistulae Prosthetic dehiscence

Invasive infection more common in aortic position and if onset is early

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Pathophysiology
Turbulent blood flow within the heart - most often (but not always) patient has risk factors for this Turbulent blood flow disrupts valve surface (endocardium) to produce suitable (sticky) site for bacterial attachment Platelet deposition + fibrin may lead to non-bacterial thrombus or vegetation Bacteraemia delivers organisms to the damaged (sticky) endocardial surface resulting in adherence & colonisation Eventual invasion of valve leaflets results in infected vegetation (sheath of fibrin & platelets, ideal conditions for further bacterial multiplications, protection from polymorphs) 21-06-2013 Dr.T.V.Rao MD 16

Infected vs Normal Valve

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Local Spread of Infection

Acute S. aureus IE with perforation of the Acute S. aureus IE with mitral valve ring aortic valve and aortic valve vegetation. abscess extending into myocardium.

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Turbulent Blood Flow

Rheumatic fever history Old age calcified valves Mitral valve prolapse with regurgitation Prosthetic heart valves Congenital defects / any structural defect Cardiac surgery Central lines Pacemakers Intravenous drug abuse
Varying predisposing conditions exist, but in over 50% of cases, no identified valvular lesion can be found.

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Distinction between Acute and Subacute Bacterial Endocarditis

Feature
Underlying Heart Disease Organism

Acute
Heart may be normal S. aureus, Pneumococcus S. pyogenes, Enterococcus Prompt, vigorous and initiated on empirical ground

Subacute
RHD,CHD, etc. viridans Streptococci, Entercoccus Can often be delayed until culture reports and susceptibilities available
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Therapy

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Bacterial Endocarditis

Clinical Features
1. 2. 3. 4. 5. 6. 7. 8. Fever. Antibiotics, salicylates, steroids, severe CHF, uremia may mask temperature elevations. Murmurs Petechial and cutaneous manifestations. Roth spots Conjunctival and mucosal petechiae, splinter hemorrhages, Osler nodes and Janway lesions. Splenomegaly Embolism. Septic or sterile. CNS, spleen, lung, retinal vessels, coronary artery, large vessels. Renal disease, infarction. Multiple abscesses. Glomerulonephritis and uremia CHF General. Weight loss, anorexia, debilitation, loss of libido.
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Symptoms
Acute
High grade fever and chills SOB Arthralgias/ myalgias Abdominal pain Pleuritic chest pain Back pain

Sub acute
Low grade fever Anorexia Weight loss Fatigue Arthralgia's/ myalgia's Abdominal pain N/V

The onset of symptoms is usually ~2 weeks or less from the initiating bacteremia
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Signs
Fever Heart murmur Nonspecific signs petechiae, subungal or splinter hemorrhages, clubbing, splenomegaly, neurologic changes More specific signs - Oslers Nodes, Janeway lesions, and Roth Spots
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Janeway Lesions

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Janeway Lesions

1. More specific 2. Erythematous, blanching macules 3. Nonpainful 4. Located on palms and soles
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Splinter Hemorrhage

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Splinter Hemorrhages

1. Nonspecific 2. Nonblanching 3. Linear reddish-brown lesions found under the nail bed 4. Usually do NOT extend the entire length of the nail
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Subconjuctival Hemorrhages

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Septic Retinal Embolus

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Roths Spots

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Oslers Nodes

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1. More specific 2. Painful and erythematous nodules 3. Located on pulp of fingers and toes Dr.T.V.Rao MD 4. More common in subacute IE

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Bacterial Endocarditis Laboratory Features

1. Anemia 2. Most commonly elevated WBC 3. ESR elevated, C in patients with glomerulonephritis 4. Microscopic hematuria 5. Bacteremia. Persistent. 3, 5 blood cultures. Aerobic and anaerobic. Different sites.
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Blood cultures
Recommendation: Blood cultures remain a cornerstone of the diagnosis of IE cases and should be taken prior to starting treatment in all case Meticulous aseptic technique is required when taking blood cultures, to reduce the risk of contamination with skin commensals, which can lead to misdiagnosis. Guidelines for best practice should be consulted
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When to Collect the blood

In patients with a chronic or sub acute presentation, three sets of optimally filled blood cultures should be taken from peripheral sites with 6 h between them prior to commencing antimicrobial therapy. Taking blood cultures at different times is critical to identifying a constant bacteraemia, a hallmark of endocarditis.
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Timing of blood collection

In patients with suspected IE and severe sepsis or septic shock at the time of presentation, two sets of optimally filled blood cultures should be taken at different times within 1 h prior to commencement of empirical therapy, to avoid undue delay in commencing empirical antimicrobial therapy.
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Start with Empherical Treatment

It is not always appropriate to withhold antimicrobial therapy while three sets of blood cultures are taken over a 12 h period. This recommendation is intended to be pragmatic, allowing time to take at least two sets of blood cultures (the minimum for a secure microbiological diagnosis) prior to commencing antimicrobial therapy.
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How to collect the Blood

Sampling of intravascular lines should be avoided, unless part of paired through-line and peripheral sampling to diagnose concurrent intravascular catheterrelated bloodstream infection.
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Longer Incubation is not Needed

In the previous BSAC guideline,1 the traditional recommendation for extended incubation and terminal subculture was maintained to increase the yield of fastidious and slow-growing bacteria, although the evidence for this was tenuous in the era of automated continuous-monitoring blood culture systems. In the light of further data and the proven utility of complementary non-culture-based technologies, the case for extended incubation and blind subculture is not justified and therefore it is not recommended
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Blood Cultures
Blood Cultures
Minimum of three blood cultures (ideally spread over 24 hrs) Three separate venipuncture sites ideally Obtain correct volume of blood for culture bottles Positive Result 1 set gives 90% sensitivity, remaining 2 sets add 8% Multiple same cultures are important in confirming significance, especially for less typical organisms Negative Result Prior antibiotic therapy Culture negative endocarditis fastidous orgs / nonculturable May support a non-endocarditis patient diagnosis
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Blood Cultures
Always need to get full identification of bacteria from positive blood cultures in suspected endocarditis Full sensitivity testing Need full MIC (minimum inhibitory concentration) for Penicillin Liaison with Lab/microbiologist in cases where endocarditis suspected/diagnosed
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Be cautious when you send multiple samples

Bacteraemia is continuous in IE rather than intermittent, so positive results from only one set out of several blood cultures should be regarded with caution.
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Prior administration of Antibiotics give

Negative Culture Results

Failure to culture a causative microorganism in IE is often due to the administration of antimicrobials prior to blood culture, but may also be due to infection caused by fastidious or slow-growing microorganisms. Diagnostic methods should include serological investigations where they are available and a systematic approach is advised, based on the clinical history of the patient and their exposure to possible risk factors.
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Culture Negative Results may yield ..less known microbes

Microorganisms that should be considered first include Coxiella burnetii (Q fever) and Bartonella spp.
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Additional Tests
CBC ESR and CRP Complement levels (C3, C4, CH50) RF Urinalysis Baseline chemistries
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Imaging
Chest x-ray
Look for multiple focal infiltrates and calcification of heart valves

ECG
Rarely diagnostic Look for evidence of ischemia, conduction delay, and arrhythmias

Echocardiography
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Indications for Echocardiography

Transthoracic echocardiography (TTE)
First line if suspected IE Native valves

Trans esophageal echocardiography (TEE)

Prosthetic valves Intracardiac complications Inadequate TTE Fungal or S. aureus or bacteremia
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Making the Diagnosis

Pelletier and Petersdorf criteria (1977)
Classification scheme of definite, probable, and possible IE
Reasonably specific but lacked sensitivity

Von Reyn criteria (1981)

Added rejected as a category
Added more clinical criteria Improved specificity and clinical utility

Duke criteria (1994)

Included the role of echocardiography in diagnosis Added IVDA as a predisposing heart condition
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Modified Duke Criteria

Definite IE
Microorganism (via culture or histology) in a valvular vegetation, embolized vegetation, or intracardiac abscess Histologic evidence of vegetation or intracardiac abscess

Possible IE
2 major 1 major and 3 minor 5 minor

Rejected IE
Resolution of illness with four days or less of antibiotics
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Bacterial Endocarditis

Therapy and Prophylaxis

1. Prolonged; high dosages; use of bactericidal drugs 2. Serum antibiotic levels and MBC of the organism 3. Viridans streptococci, Enterococcus, S. aureus, S. pneumoniae, S. pyogenes 4. Institution of therapy on empirical grounds 5. Proven negative blood cultures on Abx 6. Prophylaxis: dental extraction, GU.
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Treatment
Parenteral (IV) antibiotics
High serum concentrations to penetrate vegetation's Prolonged treatment to kill dormant bacteria clustered in vegetation's

Surgery
Intracardiac complications/paravalve abscess
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Surveillance blood cultures

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Treatment - Specific
Modify empiric therapy once cultures/sensitivities known Long duration 4-6 weeks Rx is required Refer to Trust Guidelines / BSAC Working Party Guidelines (2004) Liaise with Microbiologist Liaise with Cardiac Surgeon if needed Monitor response to treatment (clinical, CRP, ECHO) & look for complications
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Complications
Four etiologies
Embolic Local spread of infection Metastatic spread of infection Formation of immune complexes glomerulonephritis and arthritis
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Embolic Complications
Occur in up to 40% of patients with IE Predictors of embolization
Size of vegetation Left-sided vegetation's Fungal pathogens, S. aureus, and Strep. Bovis

Incidence decreases significantly after initiation of effective antibiotics

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Embolic Complications
Stroke Myocardial Infarction
Fragments of valvular vegetation or vegetationinduced stenosis of coronary ostia

Ischemic limbs Hypoxia from pulmonary emboli Abdominal pain (splenic or renal infarction)

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Metastatic Spread of Infection

Meningitis and/or encephalitis Vertebral osteomyelitis Metastatic abscess
Kidneys, spleen, brain, soft tissues

Septic arthritis
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Prevention the procedure

Dental procedures known to produce bleeding Tonsillectomy Surgery involving GI, respiratory mucosa Esophageal dilation ERCP for obstruction Gallbladder surgery Cystoscopy, urethral dilation Urethral catheter if infection present Urinary tract surgery, including prostate I&D of infected tissue

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Antibiotic Therapy
Treatment tailored to etiologic agent
Important to note MIC/MBC relationship for each causative organism and the antibiotic used High serum concentration necessary to penetrate avascular vegetation ID CONSULT EVERY TIME
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Antibiotic Therapy
Effective antimicrobial treatment should lead to defervescence within 7 10 days
Persistent fever in:
IE due to staph, pseudomonas, culture negative IE with micro vascular complications/major emboli Intracardiac/extra cardiac septic complications Drug reaction
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Prevention
Prophylactic regimen targeted against likely organism
Strep. viridans oral, respiratory, esophageal Enterococcus genitourinary, gastrointestinal S. aureus infected skin, mucosal surfaces
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Prevention the underlying lesion

High risk lesions
Prosthetic valves Prior IE Cyanotic congenital heart disease PDA AR, AS, MR,MS with MR VSD Coarctation Surgical systemic-pulmonary shunts

Intermediate risk
MVP with murmur Pure MS Tricuspid disease Pulmonary stenosis ASH Bicuspid Ao valve with no hemodynamic significance

Lesions at highest risk

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Current Trends Uncommon bacteria a concern

Endocarditis has been documented for approximately 450 years, the diagnostic challenges and treatment dilemmas are as real today as they were in the time of Fernel . Major advances have been made in the diagnosis of endocarditis, in both laboratory and clinical (imaging) parameters, but we are witnessing the emergence of several newly described causal bacterial species, such as Tropheryma whippelii and Bartonella spp., as well as sporadic case reports of unusual and uncommon causal organisms, including Finegoldia sp., Gemella 21-06-2013 Dr.T.V.Rao MD 62 spp., and Abiotrophia defective.

Molecular Methods
In addition, since diagnostic methods, mainly 16S rDNA polymerase chain reaction (PCR) and sequencing, are now beginning to identify such infections, no evidence base exists to help determine effective antimicrobial drug regimens to successfully treat endocarditis caused by such organisms. Furthermore, as specimens from many of these infections are culture-negative, conventional antibiotic susceptibility testing does not help the cardiologist decide on the most suitable antimicrobial drug regimens.
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New challenges in Endocarditis

1) the emergence of antimicrobial resistance in classic infective endocarditis microflora, namely, the grampositive cocci; 2) the existence of antimicrobial resistance in complex ecologic biofilms; 3) the changing pattern of causal agents now regarded as important pathogens of infective endocarditis, e.g., Bartonella spp., T. whippelii, and fungi; and 4) changing epidemiologic trends of persons who acquire infective endocarditis, including injection drug users, persons with HIV/AIDS, children with congenital heart defects, and persons undergoing body piercing.
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References
Emerging Issues in Infective Endocarditis Beverley C. Millar* and John E. Moore Guidelines for the diagnosis and antibiotic treatment of endocarditis in adults: a report of the Working Party of the British Society for Antimicrobial Chemotherapy F. Kate Gould etal
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 The Programme created by Dr.T.V.Rao MD for Medical Professionals in the Developing World Email
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