Infective Endocarditis

Infective Endocarditis

Tan Hong-Yong Department of Diagnosis Jining Medical College

Goals for Today  Recognize the risk factors, signs, and symptoms of infectious endocarditis.  Understand the many approaches to diagnosing infectious endocarditis.  Anticipate possible complications.  Appreciate the necessity of rapid treatment.

Anatomy of the Heart

 The heart has four valves. In counterclockwise order, they are: the aortic valve, the tricuspid valve, the pulmonary valve, and the mitral valve.

 The arrows indicate blood flow. Red arrows indicate the flow of oxygen-rich blood and blue oxygen-poor.

 Unable to facilitate the one-way flow of blood, damaged heart valves hinder

the pumping of blood efficiently throughout the body, leading to congestive heart failure. This is one reason the mortality rate of IE remains high even today.

Infective Endocarditis  General definitions and epidemiology

 Clinical manifestation

 Pathogenesis

 Complication

 Pathophysiology

 Diagnosis  Treatment

What is Infective Endocarditis (IE)?  IE is a microbial infection of the inner lining of the heart, the endocardium.

 A vegetation commonly found on the valvular leaflets is the characteristic lesion of IE.

 The incidence of IE in the United States is between 10,000 and 20,000 cases per year.

 While incidence has remained steady over the past five decades, the disease has evolved drastically.

 The mortality rate of IE is 25%.

What are the causative agents?

Principle causative agents include:

 Streptococci  Represent approximately 50% of cases of IE – down from 80% in the preantibiotic era  Viridans streptococci (30-40% of Streptococcal IE)  S. bovis account for 40%-50% of Native valve Endocarditis

 Enterococci

 Cause 5-15% of cases of IE

 Staphylococci

 Responsible for about 20% of cases of IE  Coagualse-negative staphylococci (e.g. S. aureus) cause

60% of prosthetic-valve IE  Mortality rates in prosthetic valve endocarditis have been decreasing, although the mortality rates of IE due to S. aureus remain ominously high.

S. bovis  Streptococcus bovis is a catalase- and oxidase-negative, non-motile, Gram-positive lactic acid bacterium that grows as pairs or chains of cocci.It is commonly found in the alimentary tract of cows, sheep, and other ruminants

S. aureus  S. aureus is a facultative anaerobic Gram-

positive coccus. Under the microscope they usually appear as grape-like clusters. They can be found in the air, dust, water and human faeces. S. aureus can cause a range of illnesses from minor skin infections, such as pimples, abscesses, to life-threatening diseases such as pneumonia, endocarditis, Toxic shock syndrome (TSS), and septicemia . Its incidence is from skin, soft tissue, respiratory, bone, joint, endovascular to wound infections.

Less prevalent causative agents include:

 Other bacteria  The HACEK Group  Usual bacterial causes

 Clostridium, tuberculosis, etc.  Fungi  Candida and Aspergillis species

(A number of organisms on this list are responsible for culture-negative IE)

HACEK  A HACEK organism is one of a set of slow-growing Gram negative bacteria that form a normal part of the human flora.  They are a frequent cause of endocarditis in children.

Who is susceptible to IE?

Infective Endocarditis requires bacteremia and quite often requires an underlying heart defect to be exploited by the blood-borne pathogens. With this in mind, the following groups of people are more susceptible to IE:

    

People with congenital heart defects People who have had rheumatic fever The elderly Intravenous drug users People with compromised immune systems  AIDS patients  Cancer patients

Pathogenesis  At a previously-damaged cardiac valve, a jet

stream of blood with an abnormally high velocity damages the endothelium

 This damaged surface becomes a starting point

for the deposition of platelets and the formation of a platelet-fibrin clot, causing nonbacterial thrombotic endocarditis (NBTE).

 IE develops after bacteria enter the bloodstream and colonize the clot.

Not every incidence of bacteremia leads to IE. Not only must the blood-borne pathogen be present in significant enough numbers to establish infection, it must possess the capacity (determinants of virulence) necessary to adhere to and colonize the damaged endothelium.

Local Spread of Infection

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

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

Pathogenesis  Platelets and fibrin accumulate over the

bacteria, increasing the size of the vegetation.  Leukocytes are unable to penetrate the vegetation as additional layers of fibrin are added. Treatment with antibiotics can also be problematic because the bacteria within the vegetation often become less metabolically active, and many antibiotics require active bacterial growth to be effective.

The Venturi Principle  Explains the distribution of lesions on different valves  For example, when infected blood flows from a high-pressure area (e.g. the left ventricle) through an orifice (the improperlysealed mitral valve) and into a low-pressure sink (the atrium), a Venturi effect is created. Pathogens may become engrafted on the atrial side of the mitral valve.

 A regurgitant (surging) bloodstream damages the endocardium.

But that’s not all…  The mechanisms just described pertain to subacute IE

 50-60% of cases of acute IE do not require underlying heart damage.

Being highly virulent, the organisms most responsible for acute IE (e.g. S. aureus) are able to colonize normal heart valves.

 The incidence of acute IE has been steadily

rising and now exceeds the number of subacute IE cases.

Pathophysiology  Turbulent blood flow disrupts the

endocardium making it “sticky”  Bacteremia delivers the organisms to the endocardial surface § Adherence of the organisms to the endocardial surface § Eventual invasion of the valvular leaflets

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

Clinical profile  Classification  Duke Criteria  The Essential Blood Test  Imaging  Symptoms and signs  Complications

Classification:  Acute vs. subacute  Discouraged…

 Causative agent  Native valve vs. prosthetic valve  Early prosthetic valve endocarditis vs. Late PVE  Right-sided vs. left-sided

 Culture-positive vs. culture-negative

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

The Duke Criteria

The Essential Blood Test  Blood Cultures  Minimum of three blood cultures  Three separate venipuncture sites  Obtain 10-20mL in adults and 0.5-5mL in children  Positive Result  Typical organisms present in at least 2 separate samples  Persistently positive blood culture (atypical organisms)  Two positive blood cultures obtained at least 12 hours

apart  Three or a more positive blood cultures in which the first and last samples were collected at least one hour apart

Additional Labs  CBC: increase of WBC count  ESR and CRP: elevated levels  RF: (+)  Urinalysis: hematuria or proteinuria

Imaging  Chest x-ray  Look for multiple focal infiltrates and calcification of heart valves

 EKG  

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

 Echocardiography

Echocardiography

 Types include:  Transthoracic echocardiogram (TTE)  Transesophageal echocardiogram (TEE)  The “gold standard”

The figure on the left is of a mitral valve vegetation shown by echocardiogram. The figure to the right shows one portion (called a leaflet) of the mitral valve.

Imaging  Cardiac catheterization: Discouraged…  Coronary Angiography for those over 55ys or high risk for coronary artery disease based on their coronary factors.

Clinical manifestation

          

Presenting symptoms and clinical features include: Fever Malaise Fatigue Anorexia: no appetite Weight loss Splenomegaly Cardiac murmur Petechiae Roth spots Janeway lesions Osler nodes

Some of the more diagnostic symptoms (the latter half of the above list) are occurring less frequently in patients with subacute IE, making diagnosis a greater challenge.

Osler’s Nodes

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

Petechiae 1. Nonspecific 2. Often located on extremities or mucous membranes

Splinter Hemorrhages

• • • •

Nonspecific Nonblanching Linear reddish-brown lesions found under the nail bed Usually do NOT extend the entire length of the nail

Janeway Lesions

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

Subconjunctival Hemorrhages

Roth Spots retinal hemorrhages with white or pale centers composed of coagulated fibrin.

Complications  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

Complications  Congestive heart failure is only one aspect of IE that explains the high mortality rate.

 When the vegetations grow as the infection proceeds, small pieces may break off, travel through the blood, and become lodged in other locations throughout the body. These locations include:     

The intestines The lungs The kidneys The liver The brain

 Systemic embolization is found in 22-50% of cases of IE.

How is IE diagnosed?

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

The Duke Criteria

How is IE treated?

Antimicrobial Therapy  Antibiotics are usually administered intravenously for 2-6 weeks. Duration depends on the virulence of the pathogen.

 The drug of choice for most cases of viridians streptococcal endocarditis is penicillin.  The cure rate for viridans streptococcal endocarditis is above 90%.  Without treatment, VSE is typically fatal within six months.

 Antifungals alone are not enough to cure fungal IE, although Amphotericin B is often administered in conjunction with surgery.

Antimicrobial Therapy

Antimicrobial Therapy

Antimicrobial Therapy

Antimicrobial Therapy

Surgical Treatment  15-25% of patients with IE are treated surgically  When removal of an infected valve is necessary:     

Antibiotic therapy fails (first reported case: 1965) Persistent vegetation after systemic embolization Increase in vegetation size after antimicrobial therapy Valvular dysfunction Fungal endocarditis

 “The surgeon wields a double-edged scalpel”  Surgery can introduce organisms and initiate an infection

 50% of some valvular infections do not respond to antimicrobial therapy or surgery

 Today’s highly virulent causative agents have led to an increase in dangerous complications

Can IE be prevented?

Prevention  Prophylaxis  Antibiotics may kill blood-borne bacteria or interfere with their metabolism, hindering their ability to adhere to a damaged heart valve  Controversial  Antibiotic resistance is increasing  Only administered prior to “high risk” surgeries  Include dental procedures, surgery on the gastrointestinal or urinary tract, surgery on infected tissues

 Talk to your doctor  Practice good oral hygiene

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

Poor Prognostic Factors      

Female S. aureus Vegetation size Aortic valve Prosthetic valve Older age

    

Diabetes mellitus Low serum albumen Apache II score Heart failure Paravalvular abscess  Embolic events

Case: History  2 wks of high fever, cough, green sputum, and dyspnea on exertion.

 2 wks of nausea and vomiting (5x/day), diarrhea (20x/day), and diffuse abdominal pain.

 Last IVDA 3 wks ago.

Case : History  Which symptoms does this Patient have that suggest IE?

 Does this Patient have any symptoms you can’t explain?

Case : Exam  Vitals: T 38.7, BP 100/50, HR 130, RR 48, 94%      

on finger tip Pale, distressed Petechia to palate, dry mucus membranes 2/6 SEM at 4th intercostal space with radiation to axilla Diffuse wheezing and crackles Diffuse abdominal pain and right flank pain without rebound or guarding Multiple track marks, otherwise neg. skin exam

Case : Exam  Which signs does Patient C exhibit that suggest IE?

 Does Patient C have any signs you can’t explain?

Case : Labs     

WBC 20, Platelets 66 pH 7.45, pO2 54, pCO2 27

Albumen 28 UA: 2+ protein,3+ blood EKG: within normal limits except sinus tachycardia  CXR: enlarged right heart, bilateral infiltrates with nodularity  Chest CT: multiple pulmonary abscesses

Case : Labs  Can you explain these results?  Are there other lab values you would like to know?

Case : Diagnosis  Blood Cx: three out of three bottles grew MRSA.  Initial TTE: tricuspid valve not well visualized but severe regurg. with PA systolic pressure of 55 mmHg.

 Repeat TTE (~2 wks after coding!): oscillating mass

on at least two leaflets of tricuspid valve that prolapse into R atrium during systole as well as thickened pulmonary valve with possible vegetation.

Case : Diagnosis  What major Duke criteria does this Patient meet?

 What minor Duke criteria does this Patient meet?