Infective Endocarditis

Suhail Allaqaband

Sinai Samaritan Medical Center

Milwaukee, WI

EPIDEMIOLOGY• An estimated 10,000 to 15,000 new cases of IE are

diagnosed in the United States each year • IE has increasingly become a disease of the elderly • More than one-half of all IE cases in the United States

now occur in patients over the age of 60 • This trend is probably due to two factors

– the decline in the incidence of rheumatic heart disease

– the increasing proportion of elderly subjects in the general population

RISK FACTORS • Injection drug use

– Highest risk factor in patients < 40 years of age

• Prosthetic heart valves– Prosthetic valve endocarditis comprises a small but

important segment of IE cases – More than 100,000 heart valves are implanted annually in

the United States – IE develops in 1 to 4 % of valve recipients during the 1st

year following valve replacement, and in approximately 1 percent per year thereafter

RISK FACTORS• Nosocomial endocarditis

– Usually a complication of bacteremia induced by an invasive procedure or a vascular device

• Structural heart disease – Approximately three-fourths of all patients with IE

have a preexisting structural cardiac abnormality

– Congenital heart disease is present in 10-20% cases

– The most common predisposing congenital heart lesions are bicuspid aortic valves, PDA, VSD, coarctation of the aorta, and tetralogy of Fallot

RISK FACTORS• Degenerative valvular lesions

– The risk of IE in patients with MVP and associated regurgitation is estimated to be 5 to 8 times higher than that in the normal population

– Aortic valve disease(stenosis or/and regurgitation) is present in 12 to 30 percent of cases

RISK FACTORS• History of infective endocarditis

– Recurrent endocarditis occurred in 4.5 percent of one large cohort of non-addicts

– Other studies have reported rates of IE recurrence ranging from 2.5 to 9 percent

• HIV infection – A number of cases of IE have been reported in

patients with HIV infection – It has been suggested that HIV infection is an

independent risk factor for IE in IV drug abusers

• A number of other, less common predisposing factors for IE include– Pregnancy

– AV fistulas used for hemodialysis

– Central venous and pulmonary artery catheters

– Peritoneovenous shunts for the control of ascites

– Ventriculoatrial shunts for the management of hydrocephalus

• In addition, patients with ulcerative lesions of the colon due to carcinoma or inflammatory bowel disease have a poorly understood predilection to develop endocarditis secondary to Strep.bovis

Case Definition • Duke criteria

– In 1994 investigators from Duke University modified the previous criteria to include the role of echocardiography in diagnosis

– They also expanded the category of predisposing heart conditions to include intravenous drug use

Duke Criteria• Definitive infective endocarditis

– pathologic criteria• microorganisms : demonstrated by culture or histology

in a vegetation, or in a vegetation that has embolized, or in an intracardiac abscess or

• Pathologic Lesions : vegetation or intracardiac abscess, confirmed by histology

– clinical criteria• two major criteria, or

• one major and three minor criteria, or

• five minor criteria

Duke Criteria

• Possible infective endocarditis– findings consistent of IE that fall short of “definite”,

but not “rejected”

• Rejected– firm alternate Dx for manifestation of IE

– resolution of manifestations of IE, with antibiotic therapy for 4 days

– no pathologic evidence of IE at surgery or autopsy, after antibiotic therapy for 4 days

Duke Criteria

• Major criteria– positive blood culture for IE

– evidence of endocardial involvement

• Minor criteria– predisposition (heart condition or IV drug use)

– fever of 100.40F or higher

– vascular or immunologic phenomena

– microbiologic or echocardiographic evidence not meeting major criteria

Major Criteria

• Positive blood culture for IE– typical microorganism for IE from two separate blood

cultures in the absence of a primary focus

• strep viridans, strep bovis, HACEK group, staph aureus or enterococci

• Persistently positive blood culture – blood cultures drawn more than 12 hr apart, or

– all of 3 or a majority of 4 or more separate blood cultures, with first and last drqwn at least 1 hr apart

Major Criteria

• Evidence of endocardial involvement– positive echocardiogram for endocarditis

• oscillating intracardiac mass on valve or supporting structure, or in the path of regurgitant jets, or on implanted material, in the absence of an alternate anatomic explanation

• abscess

• new partial dehiscence of prosthetic valve

– new valvular regurgitation (increase or change in pre-existing murmur not sufficient)

Minor Criteria

• predisposition – predisposing heart condition or iv drug use

• fever of 100.40F or higher

• vascular phenomena – major arterial emboli – septic pulmonary infarcts – mycotic aneurysm – intracranial hemorrhage– conjunctive hemorrhages – Janeway lesions

Duke’s Minor Criteria

• immunologic phenomena – Glomerulonephritis

– Rheumatoid factor

• microbiologic evidence – positive blood culture not meeting major criteria or

serologic evidence of active infection with organism consistent with IE

• echocardiogram – consistent with IE but not meeting major criteria

– Osler’s nodes

– Roth spots

Validity of Duke criteria • 405 consecutive cases of suspected IE were studied• 69 cases of IE were confirmed pathologically• 55 (80 percent) were clinically classified as definite using

the Duke criteria, versus only 35 being classified as probable by the von Reyn criteria

• 12 of the pathologically confirmed cases were "rejected" by the von Reyn criteria whereas none by the Duke criteriaNew criteria for diagnosis of infective endocarditis: Utilization of specific echocardiographic findings.

Duke Endocarditis Service Am J Med 1994; 96:200

Diagnostic approach to infective endocarditis • History

– A careful history should be performed with special attention given to a history of prior cardiac lesions and historical clues pointing toward a recent source of bacteremia

• Physical examination– A meticulous clinical examination should be performed looking for

clinical evidence of small and large emboli with special attention to the fundi, conjunctivae, skin, and digits

– Cardiac examination may reveal signs of new regurgitant murmurs and signs of CHF

– Neurologic evaluation may detect evidence of focal neurologic impairment

Diagnostic approach to infective endocarditis

• Positive blood culture results – A minimum of three blood cultures should be

obtained over a time period based upon the severity of the illness

• Additional laboratory tests– An elevated ESR and/or an elevated level of CRP

is usually present

– Most patients quickly develop a normochromic normocytic anemia

– The WBC count may be normal or elevated

Diagnostic approach to infective endocarditis

• Additional laboratory tests– elevated levels of serum globulins

– presence of cryoglobulins and circulating immune complexes

– hypocomplementemia

– false positive serologic tests for syphilis

– abnormal urinalysis

– microscopic or gross hematuria, proteinuria, or pyuria

– the combination of RBC casts on urinalysis and a low serum complement level may be an indicator of immune-mediated glomerular disease

Diagnostic approach to infective endocarditis

• Electrocardiogram– All patients with suspected IE should have an

EKG to determine whether there is evidence of heart block or a conduction delay and to establish a baseline should such a complication develop later

Diagnostic approach to infective endocarditis

• Echocardiography – Should be performed in all patients with suspected IE

– A TTE should initially be obtained in patients with native heart valves, while those with prosthetic valves should undergo TEE

– Detection of a vegetation by TTE is a positive test

– However, a negative study does not preclude the diagnosis and should be followed by TEE, when there is an intermediate or high suspicion of IE

Improved diagnostic value of echocardiography in patients with infective endocarditis by transoesophageal approach

A prospective study.Eur Heart J 1988 Jan;9(1):43-53

• 96 patients were studied consecutively with TEE and TTE

• TEE had a sensitivity for the detection of vegetations of 100 percent as compared to 63 percent with TTE

• Both TTE and TEE had specificity of 98%

• Only 25% of vegetations less than 5 mm, 69% of vegetations 6-10 mm, and 100% of vegetations greater than 11 mm detected by TEE were also observed with TTE

Major Pathogens• Native Valve IE

– Strep.(55%), mostly Viridans

– Staph.(30%), mostly S.aureus

– Entrococci(5-10%)

• Prosthetic Valve IE– Early (0-2 months)

• Staph(50%)- mostly S.epi.

• IE in IV drug abusers– Staph. aureus(50-60%)

– Late (>60 days)• Staph(30%)

Treatment of infective endocarditis

• GENERAL CONSIDERATIONS– Antimicrobial therapy should be administered

in a dose designed to give sustained bactericidal serum concentrations throughout much or all of the dosing interval

– In vitro determination of the minimum inhibitory concentration of the etiologic cause of the endocarditis should be performed in all patients

Treatment of infective endocarditis

• GENERAL CONSIDERATIONS – The duration of therapy has to be sufficient to

eradicate microorganisms growing within the valvular vegetations

– The need for prolonged therapy in treating endocarditis has stimulated interest in using combination therapy to treat endocarditis

VIRIDANS STREPTOCOCCI AND STREP. BOVIS

Antibiotic Dosage and route Duration Comments

Aqueous crystalline 12-18 million U/24 h 4 wks preferred in most patients older than 65 yrs

penicillin G sodium IV either continuously and in those with impairment of the eighth

or in 6 = divided doses nerve or renal function

or

Ceftriaxone sodium 2g once daily IV or IM 2 wks

Aqueous crystalline 12-18 million U/24 h 2 wks when obtained 1h after a 20-30 min.

penicillin G sodium IV either continuously IV infusion or IM injection, serum

or in six equally concentration of gentamicin of

divided doses approximately 3 mcg/mL is desirable;

with gentamicin 1 g IM or IV every 8 h 2 wks trough concentration should be < 1 pg/mL

sulfate

Vancomycin 30 mg/kg per 24 h IV 4 wks vancomycin therapy is recommended for

hydrochloride in two equally divided patients allergic to beta lactams; peak doses, not to exceed 2 serum concentrations of vancomycin should

gram/24h unless serum be obtained one h after completion of the

levels are monitored infusion and should be in the range of

30-45 mcg/mL for twice-daily dosing

JAMA 1995; 274:1706

ENTEROCOCCI

STAPH. ENDOCARDITIS IN NATIVE VALVES

STAPH. ENDOCARDITIS IN PROSTHETIC VALVES

HACEK ORGANISMS

Indications for surgery in IE • The indications for surgery in patients with native-valve

IE and prosthetic-valve IE are essentially the same • Surgery is warranted for patients with active IE who have

one or more of the following complications:– CHF that is directly related to valve dysfunction– Persistent or uncontrolled infection while receiving

appropriate antimicrobial therapy, including evidence of perivalvular extension

– Recurrent emboli, particularly in the presence of large vegetations

Indications for surgery in IE• Relative indications for surgery

– Evidence of perivalvular infection, such as intracardiac abscess or fistula formation

– Rupture of a sinus of Valsalva aneurysm– Fungal endocarditis– Endocarditis due to highly resistant microorganism– Relapse after a course of adequate antimicrobial

therapy, particularly in prosthetic valve endocarditis– Culture-negative IE with fever more than 10 days after

starting empirical therapy

Indications for surgery in prosthetic valve IE

• Same as native valve endocarditis

• Perivalvular infection

• Valve Dehiscence– excessively mobile prosthesis on echo– results in hemodynamic instability

OUTCOME OF SURGERY• The outcome of surgery in patients with IE has been good,

particularly when surgical treatment is radical with the removal of all infected and necrotic tissue

• In a recent study of 138 patients who underwent valve surgery in the presence of active infection, the early mortality, due to heart failure or septic multiorgan failure, was 11.5 %

• Risk factors for early mortality were NYHA class IV or cardiogenic shock, advanced age, preoperative acute renal failure, and staphylococcal infection

Operation for infective endocarditis: Results after implantation of mechanical valves. Ann Thorac Surg 1998; 65:359.

ACC/AHA recommendation for surgery in patients with

native valve endocarditis

ACC/AHA recommendation for surgery in patients with

prosthetic valve endocarditis

ACC/AHA recommendation for valve replacement with mechanical prosthesis

ACC/AHA recommendation forvalve replacement with bioprosthesis