11/04/2023 Dr.T.V.Rao MD 1

INFECTIVE ENDOCARDITISan update

Dr.T.V.Rao MD

11/04/2023 Dr.T.V.Rao MD 2

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.

11/04/2023 Dr.T.V.Rao MD 3

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.

11/04/2023 Dr.T.V.Rao MD 4

DefinitionInfective Endocarditis (IE): an infection of the heart’s endocardial surface

Main Classification: – Native Valve IE– Prosthetic Valve IE

Additional Consideration– Intravenous drug abuse (IVDA) IE– Nosocomial IE

11/04/2023 Dr.T.V.Rao MD 5

Infective Endocarditis• Febrile illness• Persistent bacteremia• Characteristic lesion of microbial infection of

the endothelial surface of the heart

– Variable in size– Amorphous mass of fibrin & platelets– Abundant organisms– Few inflammatory cells

The vegetation

11/04/2023 Dr.T.V.Rao MD 6

Bacterial EndocarditisPredisposing Factors

1. Dental manipulation2. Dental disease (caries, abscess)3. Extra cardiac infection (lung, urinary tract,4. skin, bone, abscess)4. Instrumentation (urinary tract, GI tract, IV

infusions)5. Cardiac surgery6. Injection drug use7. None apparent

11/04/2023 Dr.T.V.Rao MD 7

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

11/04/2023 Dr.T.V.Rao MD 8

Infective Endocarditis• Adult population

– Rheumatic Heart Disease• 20 – 25% of cases of IE in 1970’s & 80’s• 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)

11/04/2023 Dr.T.V.Rao MD 9

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)

11/04/2023 Dr.T.V.Rao MD 10

Causes of BacteraemiaBrushing teethEating/chewingDental work

IV lines (colonised/infected)IV drug use

Infected site/abscess

alpha-haemolytic streptococci from oral flora

Staphylococcus aureus from skin/nose

Strep. pneumoniae, S.aureus

11/04/2023 Dr.T.V.Rao MD 11

Infecting OrganismsCommon 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

11/04/2023 Dr.T.V.Rao MD 12

Bacterial PathogensHACEK Group

• Haemophilus spp.• Actinobacillus

actinomycetemcomitans• Cardiobacterium hominis• Eikenella corrodens• Kingella kingae

11/04/2023 Dr.T.V.Rao MD 13

Infecting OrganismsStreptococci 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 – rareCulture-negative endocarditis HACEK, Q-fever – cases do occur, subacute

11/04/2023 Dr.T.V.Rao MD 14

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)

11/04/2023 Dr.T.V.Rao MD 15

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

11/04/2023 Dr.T.V.Rao MD 16

PathophysiologyTurbulent 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 attachmentPlatelet deposition + fibrin may lead to non-bacterial thrombus or vegetationBacteraemia – delivers organisms to the damaged (sticky) endocardial surface resulting in adherence & colonisationEventual invasion of valve leaflets results in infected vegetation (sheath of fibrin & platelets, ideal conditions for further bacterial multiplications, protection from polymorphs)

11/04/2023 Dr.T.V.Rao MD 17

Infected vs Normal Valve

Local Spread of Infection

Acute S. aureus IE with perforation of the aortic valve and aortic valve vegetation.

Acute S. aureus IE with mitral valve ring abscess extending into myocardium.

11/04/2023 Dr.T.V.Rao MD 18

11/04/2023 Dr.T.V.Rao MD 19

Turbulent Blood FlowRheumatic fever historyOld age – calcified valvesMitral valve prolapse with regurgitationProsthetic heart valvesCongenital defects / any structural defectCardiac surgeryCentral linesPacemakersIntravenous drug abuse

Varying predisposing conditions exist, but in over 50% of cases, no identified valvular lesion can be found.

11/04/2023 Dr.T.V.Rao MD 20

Distinction between Acute and Subacute Bacterial Endocarditis

Feature Acute Subacute

Underlying Heart Disease

Heart may be normal RHD,CHD, etc.

Organism S. aureus, Pneumococcus S. pyogenes, Enterococcus

viridans Streptococci, Entercoccus

Therapy Prompt, vigorous and initiated on empirical ground

Can often be delayed until culture reports and susceptibilities available

11/04/2023 Dr.T.V.Rao MD 21

Bacterial Endocarditis

Clinical Features1. Fever. Antibiotics, salicylates, steroids, severe CHF, uremia may

mask temperature elevations.2. Murmurs3. Petechial and cutaneous manifestations. Roth spots Conjunctival

and mucosal petechiae, splinter hemorrhages, Osler nodes and Janway lesions.

4. Splenomegaly 5. Embolism. Septic or sterile. CNS, spleen, lung, retinal vessels,

coronary artery, large vessels.6. Renal disease, infarction. Multiple abscesses.

Glomerulonephritis and uremia7. CHF8. General. Weight loss, anorexia, debilitation, loss of libido.

11/04/2023 Dr.T.V.Rao MD 22

SymptomsAcute– 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

11/04/2023 Dr.T.V.Rao MD 23

SignsFever Heart murmurNonspecific signs – petechiae, subungal or “splinter” hemorrhages, clubbing, splenomegaly, neurologic changesMore specific signs - Osler’s Nodes, Janeway lesions, and Roth Spots

11/04/2023 Dr.T.V.Rao MD 24

Janeway Lesions

11/04/2023 Dr.T.V.Rao MD 25

Janeway Lesions

1. More specific2. Erythematous, blanching macules 3. Nonpainful4. Located on palms and soles

11/04/2023 Dr.T.V.Rao MD 26

Splinter Hemorrhage

11/04/2023 Dr.T.V.Rao MD 27

Splinter Hemorrhages

1. Nonspecific2. Nonblanching3. Linear reddish-brown lesions found under the nail bed4. Usually do NOT extend the entire length of the nail

11/04/2023 Dr.T.V.Rao MD 28

Subconjuctival Hemorrhages

11/04/2023 Dr.T.V.Rao MD 29

Septic Retinal Embolus

11/04/2023 Dr.T.V.Rao MD 30

Roth’s Spots

11/04/2023 Dr.T.V.Rao MD 31

11/04/2023 Dr.T.V.Rao MD 32

Osler’s Nodes

1. More specific2. Painful and erythematous nodules3. Located on pulp of fingers and toes4. More common in subacute IE

11/04/2023 Dr.T.V.Rao MD 33

Bacterial Endocarditis Laboratory Features

1. Anemia 2. Most commonly elevated WBC

3. ESR elevated, ↓ C′ in patients with glomerulonephritis

4. Microscopic hematuria5. Bacteremia. Persistent.≥ 3, ≤ 5 blood cultures.

Aerobic and anaerobic. Different sites.

11/04/2023 Dr.T.V.Rao MD 34

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

11/04/2023 Dr.T.V.Rao MD 35

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.

11/04/2023 Dr.T.V.Rao MD 36

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.

11/04/2023 Dr.T.V.Rao MD 37

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.

11/04/2023 Dr.T.V.Rao MD 38

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 catheter-related bloodstream infection.

11/04/2023 Dr.T.V.Rao MD 39

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

11/04/2023 Dr.T.V.Rao MD 40

Blood CulturesBlood 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 organismsNegative Result– Prior antibiotic therapy– ‘Culture negative endocarditis’ – fastidous orgs / non-

culturable– May support a non-endocarditis patient diagnosis

11/04/2023 Dr.T.V.Rao MD 41

Blood Cultures

Always need to get full identification of bacteria from positive blood cultures in suspected endocarditisFull sensitivity testingNeed full MIC (minimum inhibitory concentration) for PenicillinLiaison with Lab/microbiologist in cases where endocarditis suspected/diagnosed

11/04/2023 Dr.T.V.Rao MD 42

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.

11/04/2023 Dr.T.V.Rao MD 43

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.

11/04/2023 Dr.T.V.Rao MD 44

Culture Negative Results may yield ..less known microbes

• Microorganisms that should be considered first include Coxiella burnetii (Q fever) and Bartonella spp.

11/04/2023 Dr.T.V.Rao MD 45

Additional TestsCBCESR and CRPComplement levels (C3, C4, CH50)RFUrinalysisBaseline chemistries

11/04/2023 Dr.T.V.Rao MD 46

ImagingChest 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

11/04/2023 Dr.T.V.Rao MD 47

Indications for EchocardiographyTransthoracic 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

11/04/2023 Dr.T.V.Rao MD 48

Making the DiagnosisPelletier 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”

11/04/2023 Dr.T.V.Rao MD 49

Modified Duke CriteriaDefinite 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

11/04/2023 Dr.T.V.Rao MD 50

Bacterial EndocarditisTherapy 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 grounds5. Proven negative blood cultures on Abx6. Prophylaxis: dental extraction, GU.

11/04/2023 Dr.T.V.Rao MD 51

TreatmentParenteral (IV) antibiotics– High serum concentrations to penetrate

vegetation's– Prolonged treatment to kill dormant

bacteria clustered in vegetation's

Surgery– Intracardiac complications/paravalve

abscess

Surveillance blood cultures

11/04/2023 Dr.T.V.Rao MD 52

Treatment - SpecificModify empiric therapy once cultures/sensitivities knownLong duration 4-6 weeks Rx is requiredRefer to Trust Guidelines / BSAC Working Party Guidelines (2004)Liaise with MicrobiologistLiaise with Cardiac Surgeon if neededMonitor response to treatment (clinical, CRP, ECHO) & look for complications

11/04/2023 Dr.T.V.Rao MD 53

ComplicationsFour etiologies–Embolic–Local spread of infection–Metastatic spread of infection–Formation of immune complexes –

glomerulonephritis and arthritis

11/04/2023 Dr.T.V.Rao MD 54

Embolic Complications

Occur in up to 40% of patients with IEPredictors of embolization– Size of vegetation– Left-sided vegetation's– Fungal pathogens, S. aureus, and Strep.

Bovis

Incidence decreases significantly after initiation of effective antibiotics

11/04/2023 Dr.T.V.Rao MD 55

Embolic ComplicationsStrokeMyocardial Infarction– Fragments of valvular vegetation or vegetation-

induced stenosis of coronary ostia

Ischemic limbsHypoxia from pulmonary emboliAbdominal pain (splenic or renal infarction)

11/04/2023 Dr.T.V.Rao MD 56

Metastatic Spread of Infection

Meningitis and/or encephalitisVertebral osteomyelitisMetastatic abscess –Kidneys, spleen, brain, soft

tissuesSeptic arthritis

11/04/2023 Dr.T.V.Rao MD 57

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

11/04/2023 Dr.T.V.Rao MD 58

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

11/04/2023 Dr.T.V.Rao MD 59

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

11/04/2023 Dr.T.V.Rao MD 60

Prevention

• Prophylactic regimen targeted against likely organism– Strep. viridans – oral, respiratory,

esophageal – Enterococcus – genitourinary,

gastrointestinal– S. aureus – infected skin, mucosal surfaces

11/04/2023 Dr.T.V.Rao MD 61

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

11/04/2023 Dr.T.V.Rao MD 62

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 spp., and Abiotrophia defective.

11/04/2023 Dr.T.V.Rao MD 63

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.

11/04/2023 Dr.T.V.Rao MD 64

New challenges in Endocarditis • 1) the emergence of antimicrobial resistance in classic

infective endocarditis microflora, namely, the gram-positive 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.

11/04/2023 Dr.T.V.Rao MD 65

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

11/04/2023 Dr.T.V.Rao MD 66

• The Programme created by Dr.T.V.Rao MD for Medical

Professionals in the Developing World

• Email• doctortvrao@gmail.com