INFECTIVE ENDOCARDITIS Shehla P.Islam, M.D

INFECTIVE ENDOCARDITIS

Shehla P.Islam, M.D.Division of Infectious Diseases

University of FloridaNovemeber 3, 2010

Outline

• Epidemiology• Pathogenesis & Antibiotic prophylaxis• Clinical Manifestations• Diagnosis (TEE & Modified Duke Criteria)• Complications• Treatment (emphasis on early surgery)

Case• At midnight on July 2, your first night on call as an intern,

you’ve just admitted 5 patients and are cross-covering for your co-intern. You got a call from the micro lab. One of the patients your colleague admitted earlier that day, one set of the blood cultures is positive, growing gram positive cocci.

• The patient is a 40 y.o. female with a history of asthma. One day PTA, she was seen in the ER with several days of low grade fevers, and the initial work up was unrevealing. Blood cultures were drawn and she was sent home. She came back with persistent low grade fevers, and now has pleuritic chest pain and some shortness of breath.

Outline


Which group has the highest incidence of endocarditis?

1. Children ages 1-10 y2. Women age 20-503. Men age 20-504. Women over age 505. Men over age 50

Epidemiology

• >50% of case over age 50• male:female 1.7:1• Aortic valve and Mitral valve most common

(age dependent) Tricuspid rarer (iv drug abusers) Pulmonary valve exceedingly rare

Etiologic Agent in IE Streptococci 60-80%

Viridans Streptococci 30-40% Enterococci 5-18% Other Streptococci 15-25%

Staphylococci 20-35% Coagulase + 10-27% Coagulase - 1-3%

Gram Negative aeorobic 1.5-13% Fungi 2- 4% Culture Negative <5-24%

HACEK Fastidious organisms, slow growing

Hold blood cultures x 4 wks, Subculture on chocolate agar, 5%CO2 Haemophilus aphrophilus Actinobaccillus actinomycetemcomitans Cardiobacterium hominus Eikenella Kingella

An Additional cause of Culture Neg Tropheryma whippelii

HACEK Fastidious organisms, slow growing

Hold blood cultures x 4 wks, Subculture on chocolate agar, 5%CO2 Haemophilus aphrophilus Actinobaccillus actinomycetemcomitans Cardiobacterium hominus Eikenella Kingella

An Additional cause of Culture Neg Tropheryma whippelii

Outline

• Epidemiology• Pathogenesis• Clinical Manifestations• Diagnosis (TEE & Modified Duke Criteria)• Complications• Treatment (emphasis on early surgery)

Pathogenesis• Host factors– Nonbacterial thrombotic endocarditis (NBTE)– Venturi effect

• Bacterial factors– Bacterial adherence– Transient bacteremia

• “Vegetation”

Nonbacterial Thrombotic Endocarditis (NBTE)

• Damage to the endocardium results in the deposition of platelets, and fibrin

• Causes of endocardial damage include:1. Rheumatic heart disease (age 10-35)2. Bicuspid Valve (age 50-60) (Most common)

3. Calcific Aortic Stenosis (age 60-70)4. Mitral Valve Prolapse (murmur present)5. Marfan’s Syndrome

• No risk factor in 38% (J.Infect. 38:87-93, 1999)

PathogenesisVenturi effect

Pressure gradient required producing a high-velocity jet stream.

The high flow results in a Venturi effect (a low pressure area adjacent to the area of high flow)

Bacteria to settle in this area of low pressure. In mitral regurgitation on atrial side, in aortic regurgitation on aortic

side

Venturi

Bacterial Adherence

• Accounts for the preponderance of certain organisms

• Adherence of oral streptococci to NBTE may depend on the production of a complex extracellular polysaccharide, dextran.

• S. aureus: ability to destroy normal valves

All but one procedure results in significant bacteremia that can result in endocarditis?

1. Dental extraction2. Rigid bronchoscopy3. Urethal dilatation4. Transurethral prostatectomy5. Skin biopsy

Transient Bacteremia Procedure or action Dental

Dental extraction Periodontal surgery Chewing gum Tooth brushing Oral irrigation device

Upper airway Bronchoscopy Intubation

• % + Blood Cultures•

18-8532-8815-510-2627-50

•1516

Transient Bacteremia (cont) Gastrointestinal

Upper GI endosc. Sigmoidoscopy Barium Enema Liver Bx percutan.

Urologic Urethral dilatation Urethral Catheter Cystoscopy Transurethral prostatectomy

•8-120-9.5113-13

•18-3380-1712-46

The Vegetation

• Platelet fibrin complex provides a protective environment. Phagocytes incapable of entering, eliminating an important host defense

• Pathogenic bacteria often induce platelet aggregation

• Colony counts in vegetations 10 9-10 11 bacteria/g of tissue

Is Prophylaxis Useful?• Efficacy of prophylaxis has never been proven

Risk of one dental procedure causing endocarditis = 1/400 To prove efficacy would need a huge study. Who would

agree to be in the placebo group? • No relationship between bleeding during dental procedure

and bacteremia• Amoxacillin po 1 hr. before the procedure only for high risk

patients – prosthetic material– prior endocarditis– congenital heart disease

• Use bacteriocidal abtibiotics – time it so that peak serum level is at the time of the procedure

Outline


Case (back to the patient)• You decided that you want to get more hx• She tells you that 2 week prior to

admission, she had removed a splinter from her foot. Over the past week, she has low grade fevers, malaise, and generalized weakness, but no pulmonary/GI/GU Sx

What is the most common symptom associated with endocarditis?

1. Shortness of breath2. Chest pain3. Fatigue4. Low grade fever5. Chills6. Anorexia

How long after the inciting bacteremia does it take for a patient to develop symptoms?

1. < 2 days2. < 1 week3. < 2 weeks4. < 3 weeks5. One month

Clinical Manifestations

Incubation period usually < 2 wks Time of onset of symptoms until Rx 4-5 wks Hx: Fever 80% Fatigue

History in Infective Endocarditis

FeverChillsWeaknessSweatsAnorexiaWeight lossMalaiseCoughArthralgia/MyalgiaBack pain

80%40%40%25%25%25%25%25%15%10%

Physical Findings in IE Fever

Heart murmurEmbolic phenomenonSkin manifestations Oslers nodes-immunologic

Splinters Petechiae Janeway lesion-embolic

SplenomegallyClubbingRetinal lesion

90% 85%>50% 18-50% 10-23% 15% 20-40% <10% 20-57% 12-52% 2-10%

Case• You decided to review her admission lab

values– WBC 9.0– Hct 30 (MCV 90)– Cr 1.2– ESR 95

• Q: WBC count is normal, this is unusual for IE– 1. True– 2. False

Laboratory Findings in IE

Normochromic, Normocytic anemia (90%) WBC usually normal, can be increased High ESR (90-100%) Positive Rheumatoid factor (50%) Hypergammaglobulinemia (20-30%)

(false positive lyme or VDRL serology) Proteinuria (50-65%), hematuria (30-50%)

Outline


Modified Duke Criteria for Diagnosis of IE

(Clin. Inf. Dis. 30:633, 2000)

• Definite Infective Endocarditis- 2 major- 1 major & 3 minor- 5 minor

• Possible Infective Endocarditis- 1 major & 1 minor - 3 minor

Major Criteria• + Blood cultures for endocarditis

- 2 separate + B.C. with typical organisms including S. aureus associated with line sepsis (OR)- Persistent (2 + 12 h apart or 3 + over 1 h)

• Evidence of endocardial involvement+ echo (patients with Possible IE a TEE is recommended) (OR)- new regurgitant murmur

• Positive Q fever serology or single +BCx for Coxiella burnetii

Minor Criteria

• Predisposing heart condition or IVDU• Fever > 38°C• Vascular phenomenon• Immunologic phenomenon • Single positive BC with typical organism

Case• The next day right before rounds, you got

another call from the micro lab. Both sets of initial BCx are growing gm pos cocci in clusters

• What would you do at this time?1. This is bacterial endocarditis; I’d start her on vancomycin

STAT2. draw one more set of blood cultures to be sure, and start

her on vancomycin3. draw 2 more sets of blood cultures, and start her on

vancomycin4. could be a contaminant; I’d draw 2 more sets of blood

cultures and hold off on abx5. it’s probably a contaminant (coag negative staph); hold off

on abx, order tylenol STAT, and go back to bed

Quantitation of Bacteremia in IE

Abscess

Endocarditis

Time (hrs)

Blood Cultures in IE• Blood Cultures (15 min intervals)

Yield 85-95% on 1st BC 95-100% on the 2nd

• Recommend 3 BC in the 1st 24 hrs. • Low level bacteremia, 100 bacteria/ml

Draw at least 10 ml/BC• If HACEK group suspected hold 4 wks.• Prior antibiotics within 2 wks

lower sensitivity

What is your next step to confirm the diagnosis of

endocarditis?• 1. order EKG• 2. draw more blood cultures• 3. order TTE (transthoracic echo)• 4. order TEE (transesophageal echo)• 5. order both TTE and TEE• 6. call infectious disease consult• 7. call cardiology consult

Cardiac Echo in IE• Transthoracic(TTE): sensitivity 65%

If negative order a transesophageal echo• Transesophageal(TEE): sensitivity 95-100%

Can detect vegetations < 10 mmHelpful in assessing the need for surgeryDetects perivalvular extensionUse in the initial evaluation for suspected IE(if prior probability 4-60%) (useful in S. aureus line sepsis 2 vs 4 wk abx)

Outline


Cardiac Complications of IE Congestive Heart Failure Myocardial abscess/pericarditis Conduction defects can progress to complete

heart block (which valve most commonly is associated with this complication?)

Myocardial Infarction

Other Complications of IE

• Emboli - CNS, Splenic, Lung (Rt sided IE)• Immune-complex glomerulonephritis• Mycotic aneurysms

Occur at bifurcations -Middle cerebral artery

-Adominal aorta-Mesenteric arteries

Case• Initial blood cultures identified as MSSA• TTE showed a small vegetation on the

tricuspid valve, there is no abscess• She is currently on vancomycin, what

would you do?1. Penicillin 20 million units per day x 6 weeks2. Oxacillin 10 gms per day x 4 weeks3. Doxycycline 100 mg iv twice per day x 4 weeks4. Penicillin 20 million units per day combined with gentamicin 80 mg 3 x per day x 2

weeks5. Chloramphenicol 400 mg four times per day x 4 weeks6. Ceftriaxone 1 gm per day x 6 weeks

“I found the antibiotic therapy for infective endocarditis section difficult and slightly overwhelming.”

Conclusions:Infective Endocarditis

Usually requires an NBTE except S. aureus Organisms that cause IE increased adherence Clinical symptoms usually nonspecific Always look for embolic lesions Duke criterion, importance of timed Blood

Cultures, use of TEE Privileged environment of vegetation requires

prolonged cidal antibiotics Low threshold for surgery

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INFECTIVE ENDOCARDITIS Shehla P.Islam, M.D