Infective Endocarditis for 9th semister MBBS

Dr Rajesh Padhi, M.D., Fellowship in Diabetilogy CMC Vellore, PGCC Cardiology.

Infective Endocarditis
Essential characteristics General definitions and epidemiology
NVE I.V. drug abuse PVE

Pathophysiology Clinical features Treatment

Pathogenesis

Infective Endocarditis
Infectious endocarditis (IE) denotes infection of the endocardial surface of the heart and implies the physical presence of microorganisms in the lesion 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

Definition of IE According to the Modified Duke Criteria

Major criteria 1 Blood culture positive for IE Typical microorganisms consistent with IE from two separate blood cultures: Viridans streptococci, Streptococcus bovis, HACEK group, Staphylococcus aureus; or Community-acquired enterococci in the absence of a primary focus; or Microorganisms consistent with IE from persistently positive blood cultures, defined as follows: At least two positive cultures of blood samples drawn more than 12 h apart; or All of three or a majority of greater than four separate cultures of blood (with first and last sample drawn at least 1 h apart) Single positive blood culture for Coxiella burnetti or antiphase 1 IgG antibody titer greater than 1:800

Definition of IE According to the Modified Duke Criteria contd..

Major Criteria 2 Evidence of endocardial involvement Echocardiogram positive for IE (TEE recommended in patients with prosthetic valves, rated at least "possible IE" by clinical criteria, or complicated IE [paravalvular abscess]; TTE as first test in other patients), defined as follows: Oscillating intracardiac mass on valve or supporting structures, in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomic explanation; or Abscess; or New partial dehiscence of prosthetic valve New valvular regurgitation (worsening or changing of preexisting murmur not sufficient)

Definition of IE According to the Modified Duke Criteria contd..

1.
2. 3.

4.

5.

6.

Minor criteria Predisposition, predisposing heart condition, or injection drug use Fever, temperature greater than 100.4F (38C) Vascular phenomena, major arterial emboli, septic pulmonary infarcts, mycotic aneurysm, intracranial hemorrhage, conjunctival hemorrhages, and Janeway lesions Immunologic phenomena; glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor Microbiologic evidence: positive blood culture but does not meet a major criterion,a or serologic evidence of active infection with organism consistent with IE Echocardiographic minor criteria eliminated

Definition of IE According to the Modified Duke Criteria contd..

Definite infective endocarditis Pathologic criteria 1. Microorganisms demonstrated by culture or histologic examination of a vegetation, a vegetation that has embolized, or an intracardiac abscess specimen; or 2. 2. Pathologic lesions; vegetation, or intracardiac abscess confirmed by histologic examination showing active endocarditis

Definition of IE According to the Modified Duke Criteria contd.. Definite infective endocarditis Clinical criteria 1. Two major criteria; or 2. 2. One major criterion and three minor criteria; or 3. 3. Five minor criteria

Definition of IE According to the Modified Duke Criteria contd..

1. 2.
1. 2. 3.

4.

Possible infective endocarditis One major criterion and one minor criterion; or Three minor criteria Rejected Firm alternate diagnosis explaining evidence of infective endocarditis; or Resolution of infective endocarditis syndrome with antibiotic therapy for less than 4 days; or No pathologic evidence of infective endocarditis at surgery or autopsy, with antibiotic therapy for less than 4 days; or Does not meet criteria for possible infective endocarditis, as noted above

Classification:
1-Acute:
- Aggressive.
- Virulent organisms such as Staph. Aureus. - Often affects the normal valves.

2- Subacute:
- Indolent course over weeks to months. - Less virulent organisms such as Strep. Viridans. - Usually develops on abnormal valves.

3- Early Prosthetic Valve Endocarditis (EPVE): - Infection of the artificial valves within 2 months after surgery.

4- Late Prosthetic Valve Endocarditis (LPVE):

-Infection of the artificial valves > 2 months after surgery.

5- Non - Bacterial Thrombotic Endocarditis (NBTE). - Any endocardial sterile vegetations wide spectrum.

Etiology:
NBTE:
- Endothelial damage leads to platelet aggregation and deposition with Fibrin and development of sterile vegetations.

ABE/SBE:
- Microbes probably colonize the pre-existing NBTE or even invade endothelium in the case of ABE.

MV > AV >TV >PV. Drug Abusers:

- TV, MV, AV, PV. Infection of vegetations Friability and Embolic Phenomena. Immunological Phenomena.

Causative organisms:
1- ABE:
- Staph. AUreus. - Strep. Pneumonia. - Hemophilus Influenza. - enterococcal Species. - Strep. Bovis. - HACEK group. - Staph. Aureus. - Gram -ve. Rods (E-Coli, Pseudomonas). - Enterococci (S. Bovis & Fecalis). - Candidiasis. - Enterococci.

2- SBE:
- Strep. Viridans. - Enterococcal Species.

3- EPVE:
- Staph. Epidermedis. - Asperigillus Species.

4- LPVE:
- St. Viridans.

5- Drug Abusers:
- Staph. Aureus. - Pseudomonas & E-coli.

Risk Factors:
1- High Risk:
- Prosthetic Heart Valves.
- Previous Endocarditis. - Congenital cyanotic heart disease. - MR. - AR. - VSD. - PDA. - Coarctation of the Aorta.

Risk Factors:contd..
2- Intermediate Risk:
- MVP with mild MR. - Pure MS. - TVD. - PVD. - HOCM (IHSS). - AS. - Non-Valvular prosthetic cardiac implants. - Intracardiac catheters.

3- Low Risk:
- ASD ( Ostium secundum Type). - MVP without MR.

4- Other Risk Factors:

- IV. Drug abuse. - AV shunts for hemodialysis. - Massive Wounds such as burns.

CLINICAL PICTURE:
- Fever: Low grade in SBE. High grade in ABE. - Pallor: Anemia. - chills, rigors and sweating. - Malaise and anorexia. - New murmurs or increasing the grade of an old murmurs. - Murmurs may be absent in severe cases. - Focal neurological signs ( embolic phenomena or meningitis ). - Delerium and headache. - Chest pain, dyspnea, cough and hemoptysis.

CLINICAL PICTURE (contd):

- Flank pain, hematuria, left upper quadrant pain evidence of distal emboli or Immune Complex Glomerulo- Nephritis. - Cold painful extremity. - Splenomegaly. - Peticheal hemorrhage. - Oslers nodules. - Splinter Hge. - Janeway lesions. - Finger clubbing. - Roths Spots in the retina. - Conjunctival hemorrhage. - Rales and gallop.

INFECTIVE ENDOCARDITIS

INFECTIVE ENDOCARDITIS

INFECTIVE ENDOCARDITIS

Important Definitions
Endarteritis - Inflammation of the intima of an artery. Janeway lesion - Erythematous, nontender lesions on fingers, palm, or sole. Mycotic aneurysms - Aneurysmal dilatation of a vessel caused by invasion of the vascular wall from infective endocarditis. Osler nodes - Small, tender, purple erythematous subcutaneous nodules visibly found on the pulp of digits. Roth spots - Retinal hemorrhages with a clear center. Splinter hemorrhage - An embolic subungual hemorrhage located proximally in the nail bed. Vegetations - Growth consisting of fused platelets, fibrin, and other bacteria adherent to a heart valve or other vascular structure.

Infective Endocarditis
Typically involves the valves
May involve all structures of the heart
Chordae tendinae Sites of shunting Mural lesions

Infection of vascular shunts, by strict definition, is endarteritis, but lesion is the same

Majority of cases caused by streptococcus, staphylococcus, enterococcus, or fastidious gram negative cocco-bacillary forms

Infective Endocarditis
Gram negative organisms
P. aeruginosa most common HACEK - slow growing, fastidious organisms that may need 3 weeks to grow out of culture
Haemophilus sp. Actinobacillus Cardiobacterium Eikenella Kingella

Infective Endocarditis
Acute
Toxic presentation Progressive valve destruction & metastatic infection developing in days to weeks Most commonly caused by S. aureus

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

Infective Endocarditis
Case rate may vary between 2-3 cases /100,000 to as high as 15-30/100,000 depending on incidence of i.v. drug abuse and age of the population
55-75% of patients with native valve endocarditis (NVE) have underlying valve abnormalities
MVP Rheumatic Congenital ASH or: i.v. drug abuse

Infective Endocarditis
Case rates
7-25% of cases involve prosthetic valves 25-45% of cases predisposing condition can not be identified

Infective Endocarditis
Pediatric population
The vast majority (75-90%) of cases after the neonatal period are associated with an underlying congenital abnormality
Aortic valve VSD Tetralogy of Fallot

Risk of post-op infection in children with IE is 50%

Microbiology
Neonates: S. aureus, coag staph, group B strep Older children: 40% strep, S. aureus

Infective Endocarditis
Adult population
MVP prominent predisposing factor
High prevalence in population
2-4% 20% in young women

Accounts for 7 30% NVE in cases not related to drug abuse or nosocomial infection

Relative risk in MVP ~3.5 8.2, largely confined to patients with murmur, but also increased in men and patients >45 years old
MVP with murmur MVP w/o murmur incidence IE 52/100/000 pt. years incidence IE 4.6/100,000 pt. years

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)

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%, 6070% of tricuspid cases)

Infective Endocarditis
Intravenous Drug Abuse
Increased frequency of gram negative infection such as P. aeruginosa & fungal infections High concordance of HIV positivity & IE (2773%)
HIV status does not in itself modify clinical picture Survival is decreased if CD4 count < 200/mm3

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)

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

Infective Endocarditis
Pathogenesis
Endothelial damage

Platelet-fibrin thrombi

Microorganism adherence

Infective Endocarditis
Nonbacterial Thrombotic Endocarditis
Endothelial injury Hypercoagulable state
Platelet-fibrin thrombi

Lesions seen at coaptation points of valves

Atrial surface mitral/tricuspid Ventricular surface aortic/pulmonic

Modes of endothelial injury

High velocity jet Flow from high pressure to low pressure chamber Flow across narrow orifice of high velocity

Bacteria deposited on edges of low pressure sink or site of jet impaction Venturi Effect

Venturi Effect

Conversion of NBTE to IE
Frequency & magnitude of bacteremia
Density of colonizing bacteria
Oral > GU > GI

Disease state of surface

Infected surface > colonized surface

Extent of trauma

Resistance of organism to host defenses

Most aerobic gram negatives susceptible to complementmediated bactericidal effect of serum Tendency to adhere to endothelium
Dextran producing strep Fibronectin receptors on staph, enterococcus, strep, Candida

Pathophysiology
Clinical manifestations
Direct
Constitutional symptoms of infection (cytokine)

Indirect
Local destructive effects of infection Embolization septic or bland Hematogenous seeding of infection
N.B. may present as local infection or persistent fever, metastatic abscesses may be small, miliary

Immune response
Immune complex or complement-mediated

Pathophysiology
Local destructive effects
Valvular distortion/destruction Chordal rupture Perforation/fistula formation Paravalvular abscess Conduction abnormalities Purulent pericarditis Functional valve obstruction

Pathophysiology
Embolization
Clinically evident 11 43% of patients Pathologically present 45 65% High risk for embolization
Large > 10 mm vegetation Hypermobile vegetation Mitral vegetations (esp. anterior leaflet)

Pulmonary (septic) 65 75% of i.v. drug abusers with tricuspid IE

Clinical Features
Interval between index bacteremia & onset of sxs usually < 2 weeks
May be substantially longer in early PVE

Fever most common sign

May be absent in elderly/debilitated pt.

Murmur present in 80 85%

Generally indication of underlying lesion Frequently absent in tricuspid IE

Changing murmur

Classical Peripheral Manifestations

Less common today
Not seen in tricuspid endocarditis Petechiae most common

Janeway Lesions

Splinter Hemorrhage

Oslers Nodes

Subconjunctival Hemorrhages

Roths Spots

Clinical Features
Systemic emboli
Incidence decreases with effective anti-microbial Rx

Neurological sequelae
Embolic stroke 15 20% of patients Mycotic aneurysm Cerebritis

CHF
Due to mechanical disruption High mortality without surgical intervention

Renal insufficiency
Immune complex mediated Impaired hemodynamics/drug toxicity

Diagnosis
Published criteria for diagnostic purposes in obscure cases High index of suspicion in patients with predisposing anatomy or behavior Blood cultures Echocardiography
TTE 60% sensitivity TEE 80 95% sensitive

Goals of Therapy
1. Eradicate infection

2. Definitively treat sequelae of destructive

intra-cardiac and extra-cardiac lesions

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

Antibiotic Therapy
Treatment before blood cultures turn positive
Suspected ABE Hemodynamic instability

Neither appropriate nor necessary in patient with suspected SBE who is hemodynamically stable

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 microvascular complications/major emboli Intracardiac/extracardiac septic complications Drug reaction

Surgical Treatment of IntraCardiac Complications

NYHA Class III/IV CHF due to valve dysfunction
Surgical mortality 20-40% Medical mortality 50-90%

Unstable prosthetic valve

Surgical mortality 15-55% Medical mortality near 100% at 6 months

Uncontrolled infection

Surgical Treatment of IntraCardiac Complications

Unavailable effective antimicrobial therapy
Fungal endocarditis Brucella

S. aureus PVE with any intra-cardiac complication Relapse of PVE after optimal therapy

Surgical Treatment of IntraCardiac Complications

Relative indications
Perivalvular extension of infection Poorly responsive S. aureus NVE Relapse of NVE Culture negative NVE/PVE with persistent fever (> 10 days) Large (> 10mm) or hypermobile vegetation Endocarditis due to highly resistant enterococcus

Prevention
Prophylactic regimen targeted against likely organism
Strep. viridans oral, respiratory, eosphogeal Enterococcus genitourinary, gastrointestinal S. aureus infected skin, mucosal surfaces

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

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 systemicpulmonary shunts
Lesions at highest risk

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

Prevention the underlying lesion

Low/no risk
MVP without murmur Trivial valvular regurg. Isolated ASD Implanted device (pacer, ICD) CAD CABG

This wallet card is to be given to patients by their physician. Healthcare professionals, please see back of card for reference to the complete statement.

Name: ____________________________________________ needs protection from BACTERIAL ENDOCARDITIS because of an existing HEART CONDITION Diagnosis: __________________________________________ Prescribed by: _______________________________________ Date: ______________________________________________

Chemoprophylaxis
Adult Prophylaxis: Dental, Oral, Respiratory, Esophageal Standard Regimen Amoxicillin 2g PO 1h before procedure or Ampicillin 2g IM/IV 30m before procedure Penicillin Allergic Clindamycin 600 mg PO 1h before procedure or 600 mg IV 30m before Cephalexin OR Cefadroxil 2g PO 1 hour before Cefazolin 1.0g IM/IV 30 min before procedure Azithromycin or Clarithromycin 500mg PO 1h before

Adult Genitourinary or Gastrointestinal Procedures

High Risk Patients Standard Regimen Before procedure (30 minutes): Ampicillin 2g IV/IM AND Gentamicin 1.5 mg/kg (MAX 120 mg) IM/IV After procedure (6 hours later) Ampicillin 1g IM/IV OR Amoxicillin 1g PO Penicillin Allergic Complete infusion 30 minutes before procedure Vancomycin 1g IV over 1-2h AND Gentamicin 1.5 mg/kg IV/IM (MAX 120 mg) Moderate Risk Patients

Standard Regimen Amoxicillin 2g PO 1h before OR Ampicillin 2g IM/IV 30m before Penicillin Allergic Vancomycin 1g IV over 1-2h, complete 30m before

Summary
You need to go to medical school (and graduate) in order to take care of patients with endocarditis.