INFECTIVE ENDOCARDITIS

AKINPELU A.J.

OUTLINE• INTRODUCTION• BACKGROUND• EPIDEMIOLOGY • CLASSIFICATION• PREDISPOSING/RISK FACTORS• PATHOGENESIS• SIGNS/SYMPTOMS• DIAGNOSIS• TREATMENT• COMPLICATIONS • PREVENTION• PROGNOSIS • CONCLUSION

INTRODUCTION

• Infective endocarditis (IE) is defined as an infection of the endocardial surface of the heart, which may include one or more heart valves, the mural endocardium or a septal defect.

• Its intracardiac effects include severe valvular insufficiency, which may lead to intractable congestive heart failure, and myocardial abscesses.

BACKGROUND

• Lazaire Riviere first described gross autopsy findings of the disease in 1723.

• In 1885, William Osler presented the first comprehensive description of endocarditis in English.

• Lerner and Weinstein presented a thorough discussion of this disease in modern times.

• Endocarditis has evolved into several variations, keeping it near the top of the list of diseases that must not be misdiagnosed or overlooked.

• Currently, infection of intravascular lines has been determined to be the primary risk factor for Staphylococcus aureus bloodstream infections (BSIs).

• Since the 1960s, the clinical characteristics of IE have changed due to increase in recreational drug use and of invasive vascular procedures.

• Varieties of IE that were uncommon in the early antibiotic era have become prominent(NIE, IVDA IE, PVE)

EPIDEMIOLOGY • In the United States, the 2009 incidence of IE was

approximately 12.7 cases per 100,000 persons per year.

• This incidence has significantly risen from that of the previous 50 years which was 2-4 cases per 100,000 persons per year.

• The incidence in other countries is similar to that in the United States from 1998-2009

• It is 3 times as common in males as in females• No racial predilection• It may occur in a person of any age.

• Between 1998 and 2009, the mean age of patients has risen from 58 to 60 years. (Mendiratta et al.)

• In children it accounts for 4.6% of AHD in Nigeria.• The proportion of people with intracardiac devices

increased from 13.3% to 18.9% while the proportion of cases with a background of HIV drug abuse fell.

• Rheumatic heart disease currently accounts for less than 20% of cases, and 6% of patients with rheumatic heart disease eventually develop IE.

• A retrospective study (Jan 1982 to Dec 1989) of infective endocarditis in 32 cases from ABUTH, Zaria, Nigeria, found – underlying heart disease in 30 patients (90%), where – 21 cases (66%) had RHD and – nine cases (28%) had underlying congenital heart

diseases. – Overall mortality was 47% due mostly to heart

failure and neurological complications.

CLASSIFICATION

• Acute (short incubation) vs. subacute (long incubation)

• Culture-positive vs. culture-negative• Right sided vs. left sided• Nosocomial vs. community-acquired• Native-valve endocarditis vs. prosthetic-valve

CLASSIFICATION • Native valve endocarditis (NVE),

– acute and – subacute

• Prosthetic valve endocarditis (PVE), – early and – late

• Intravenous drug abuse (IVDA) IE• Nosocomial IE (NIE)• Pacemaker IE • Culture positive and culture negative IE

Native valve endocarditis• Rheumatic valvular disease (30% of NVE) - Primarily involves

the mitral valve followed by the aortic valve• Congenital heart disease (15% of NVE) - Underlying etiologies

include – patent ductus arteriosus, – ventricular septal defect, – tetralogy of Fallot,– native or surgical high-flow lesion.

• Mitral valve prolapse with an associated murmur (20% of NVE)• Degenerative heart disease - Including calcific aortic stenosis

due to a bicuspid valve or syphilitic disease

Native valve endocarditis

• Acute bacterial endocarditis (ABE) • fulminant illness over days to weeks • more likely due to Staphylococcus aureus and group B

Streptococci which has much greater virulence, or disease-producing capacity

• frequently causes metastatic infection by hematogenous seeding

• Destructive • frequently of a previously normal heart valve• leads to death within weeks if left untreated

• Subacute bacterial endocarditis (SBE) – often due to alpha hemolytic streptococci and

enterococci of low virulence – mild to moderate insidious illness which progresses

slowly over weeks and months – low propensity to hematogenously seed to

extracardiac sites– previously abnormal heart, particularly on deformed

valves– recover after appropriate antibiotic treatment

Prosthetic valve endocarditis• PVE accounts for 10-20% of cases of IE. • Eventually, 5% of prosthetic valves become infected. • Mechanical valves are more likely to be infected within the

first 3 months of implantation• Bioprosthetic valves are more likely to be infected after one

year• The valves in the mitral valve position are more susceptible

than those in the aortic areas• Recent data suggest that S aureus may now be the most

common infecting organism in both early and late PVE

• Early PVE occurs within 60 days of valve implantation– usually due to intraoperative contamination or a postoperative

bacterial contamination which is usually nosocomial in nature. – coagulase-negative staphylococci, gram-negative bacilli, and

Candida species most common.

• Late PVE occurs 60 days or more after valve implantation – Late prosthetic valve endocarditis is usually due to community

acquired microorganisms– Staphylococci, alpha-hemolytic streptococci, and enterococci

are the common causative organisms.

Intravenous drug abuse endocarditis

• No underlying valvular abnormalities are noted in 75% of cases

• 50% of these infections involve the tricuspid valve

• S. aureus is the most common causative organism

Nosocomial infective endocarditis

• NIE is defined as an infection that manifests 48 hours after the patient is hospitalized or that is associated with a hospital, based on a procedure performed within 4 weeks of clinical disease onset.

• The term healthcare-associated infective endocarditis (HCIE) is preferable to NIE, since it is inclusive of all sites that deliver patient care, such as hemodialysis centers.

• An appropriate alternative term would be iatrogenic IE.

– The right-sided variety affects a valve that has been injured by placement of an intravascular line

– The left sided variety develops in a previously damaged valve.

• S aureus has been the predominant pathogen of NIE/HCIE since the recent prevalence of intravascular devices.

• Enterococci are second most commonly isolated pathogens usually from a genitourinary source.

Pacemaker infective endocarditis

• Infections of implantable pacemakers and cardioverter defibrillators.

• They are infected within a few months of implantation– Generator pocket (most common)– Proximal leads– Portion of leads in direct contact with endocardium, this

represents true pacemaker IE, is the least common (0.5% of implanted pacemakers), and is the most challenging to treat.

• Of pacemaker infections, 75% are produced by staphylococci

• Risk factors for the development of pacemaker IE– Surgical intervention to any part of the pacemaker system,

especially elective battery replacements. Approximately 5 times the risk of initial implantation (6.5% vs 1.4%)

– Diabetes mellitus– Age– Use of anticoagulants and corticosteroids– Postoperative hematoma – Inexperience of the surgeon– Preceding temporary transvenous pacing

Culture positive and culture negative endocarditis

• Culture-negative endocarditis can be due to – micro-organisms that require a longer period of

time to be identified in the laboratory– Fastidious organisms Aspergillus species, Brucella

species, Coxiella burnetii, Chlamydia species, and HACEK bacteria.

– Fungal endocarditis– Surface sterilization in S.aureus IE– Prior antibiotic treatment.

PREDISPOSING/RISK FACTORS

• The most significant risk factor for IE is residual valvular damage caused by a previous attack of endocarditis.

• IVDA• Prosthetic heart valves• Structural heart disease: mitral valve prolapse with

mitral regurgitation and aortic stenosis. • Congenital heart defects: Tetralogy of Fallot, bicuspid

aortic valves, Coarctation of the aorta, VSDs, and patent ductus arteriosus.

PREDISPOSING/RISK FACTORS• A predisposing abnormality of the endocardium

• RHD(8.5% in Nigeria)• Myxomatous mitral valve• Hypertrophic cardiomyopathy• Degenerative calcific valvular stenosis• Valvular damage from surgery, autoimmune conditions or old age.

• Host factors• Neutropenia• Immunodeficiency• Malignancy• Therapeutic immunosuppression• Diabetes mellitus• Alcohol• IV drug abuse

PATHOPHYSIOLOGY• Turbulent 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 attachment• Platelet deposition + fibrin may lead to non-bacterial thrombus

or vegetation(NBTE) providing a nidus for bacterial adhesion.• Bacteraemia – delivers organisms to the damaged (sticky)

endocardial surface resulting in adherence & colonisation.• Eventual invasion of valve leaflets results in infected vegetation

(sheath of fibrin & platelets, ideal conditions for further bacterial multiplications, protection from polymorphs)

Bacteremia • Most commonly from gingival disease.• Pneumonias or pyelonephritis• Most cases of subacute disease are secondary to the

bacteremias that develop from the activities of daily living (e.g.brushing teeth).

• S aureus infection due to production of alpha toxin which allows the organism to penetrate the keratinocyte layer in the absence of any gross damage to the epithelial layer.

• Endotheliosis by S aureus can increase the expression of adhesion molecules and of procoagulant activity on the cellular surface.

Invasive procedures• Dental extractions - Rate of 40-100%; S viridans• Transurethral resection of the prostate - Rate of 20-40%; coliforms,

enterococci, S aureus• Endoscopy - Rate of 0-20%; coagulase-negative staphylococci

(CoNS), streptococci, diphtheroids• Colonoscopy – Rate of 0-20%; Escherichia coli, Bacteroides species• Barium enema - Rate of 0-20%; enterococci, aerobic and anaerobic

gram-negative rods• Transesophageal echocardiography - Rate of 0-20%; S viridans,

anaerobic organisms, streptococci

Adhesion of bacteria

• Damaged vascular endothelium will also promote platelet and fibrin deposition, upon which bacteria can take hold.

• Nonbacterial thrombotic endocarditis also may result from stress, renal failure, malnutrition, systemic lupus erythematosus or neoplasia.

• In acute IE, the thrombus may be produced by the invading organism (i.e. S aureus) or by valvular trauma from intravenous catheters or pacing wires (i.e. NIE/HCIE).

Invasion of valvular leaflets • Colonization of heart valves by microorganisms is a complex

process. • Once microorganisms do establish themselves on the surface of

the vegetation, the process of platelet aggregation and fibrin deposition accelerate at the site.

• As the bacteria multiply, they are covered by ever-thickening layers of platelets and thrombin, which protect them from neutrophils and other host defenses.

• Organisms deep in the vegetation hibernate because of the paucity of available nutrients and are therefore less susceptible to bactericidal antimicrobials that interfere with bacterial cell wall synthesis.

• The cellular reaction in SBE is primarily that of mononuclear cells and lymphocytes, with few polymorphonuclear cells.

• The surface of the valve beneath the vegetation shows few organisms.

• Proliferation of capillaries and fibroblasts is marked. • Areas of healing are scattered among areas of destruction.

Over time, the healing process falls behind, and valvular insufficiency develops secondary to perforation of the cusps and damage to the chordae tendineae.

• Extension of the infectious process occurs beyond the valvular leaflets.

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.

01/05/2023 Dr.T.V.Rao MD 30

Endothelial Injury

Uninfected Platelet-Fibrin thrombus (NBTE)

Transient bacteremia and attachment at NBTE

Proliferation and pro-coagulant state

Infected, friable, bulky vegetation

MICROBIOLOGY• Staphylococcus aureus

– most common cause of IE, including PVE, acute IE, and IVDA IE.

– Approximately 35-60.5% of staphylococcal bacteremias are complicated by IE.

– More than half the cases are not associated with underlying valvular disease.

– The mortality rate of S aureus IE is 40-50%. • Streptococcus viridans

– This organism accounts for approximately 50-60% of cases of subacute disease.

– Most clinical signs and symptoms are mediated immunologically.

• Streptococcus intermedius group – These infections may be acute or subacute.– S intermedius infection accounts for 15% of streptococcal

IE cases. – S intermedius is unique among the streptococci; it can

actively invade tissue and can cause abscesses. • Abiotrophia species (formerly known as nutritionally variant

streptococci) – Approximately 5% of subacute cases of IE. – This type of IE is associated with large vegetations that

lead to embolization and a high rate of posttreatment relapse.

• Group D streptococci– Most cases are subacute. – The source is the gastrointestinal or genitourinary tract. – It is the third most common cause of IE.– They pose major resistance problems for antibiotics.

• Nonenterococcal group D organisms – The clinical course is subacute. – Infection often reflects underlying abnormalities of the

large bowel (e.g. ulcerative colitis, polyps, cancer). – The organisms are sensitive to penicillin.

• Group B streptococci – Acute disease develops in pregnant patients and older patients with

underlying diseases (eg, cancer, diabetes, alcoholism). – The mortality rate is 40%.– Complications include metastatic infection, arterial thrombi, and

congestive heart failure.– It often requires valve replacement for cure.

• Group A, C, and G streptococci– Acute disease resembles that of S aureus IE (30-70% mortality rate),

with suppurative complications.– Group A organisms respond to penicillin alone.– Group C and G organisms require a combination of synergistic

antibiotics (as with enterococci).

• Coagulase-negative S aureus– This causes subacute disease.– It behaves similarly to S viridans infection.– It accounts for approximately 30% of PVE cases and

less than 5% of NVE cases.• Pseudomonas aeruginosa

– This is usually acute, except when it involves the right side of the heart in IVDA IE.

– Surgery is commonly required for cure.

• HACEK organisms (Haemophilus aphrophilus, Aggregatibacter actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Kingella kingae)– These organisms usually cause subacute disease. – They account for approximately 5% of IE cases.– They are the most common gram-negative organisms isolated

from patients with IE. – Complications may include massive arterial emboli and

congestive heart failure. – Cure requires ampicillin, gentamicin, and surgery.

SYMPTOMS• Symptoms commonly are vague, emphasizing constitutional complaints

– Fever and chills are the most common symptoms– anorexia, – weight loss, – malaise, – headache, – myalgias, – night sweats, – shortness of breath, – cough, – joint pains– Dyspnea, cough, and chest pain are common complaints of

intravenous drug users.

• Primary cardiac disease may present with signs of congestive heart failure due to valvular insufficiency.

• Secondary phenomena could include focal neurologic complaints due to an embolic stroke or back pain associated with vertebral osteomyelitis.

• As many as 20% of cases present with focal neurologic complaints and stroke syndromes.

Subacute Symptoms are subtle and nonspecific. • Low-grade Fever (Absent In 3-15% Of Patients),• Anorexia, • Weight Loss, • Influenza-like Syndromes, • Polymyalgia-like Syndromes, • Pleuritic Pain, • Syndromes Similar To Rheumatic Fever (Fever, Dulled Sensorium As In

Typhoid, Headaches), • Abdominal Symptoms (Right Upper Quadrant Pain, Vomiting, Postprandial

Distress, Appendicitis-like Symptoms).• Palpitations• Lumbosacral Pain

Acute

• Acute onset of high-grade fevers and chills• Rapid onset of congestive heart failure with

marked dyspnoea and fatigue.

SIGNS • The AHA (endorsed by the Infectious Diseases Society of America

[IDSA]) 2010 guideline update on cardiovascular implantable electronic device (CIED) infections and their management recommends that patients with CIED who develop unexplained fever or bloodstream infection should seek evaluation for CIED infection by cardiologists or infectious disease specialists.

• Fever, possibly low-grade and intermittent, is present in 90% of patients.

• Heart murmurs are heard in approximately 85% of patients. Change in the characteristics of a previously noted murmur occurs in 10% of these patients and increases the likelihood of secondary congestive heart failure.

• One or more classic signs of IE are found in as many as 50% of patients. They include the following:– Petechiae - Common but nonspecific finding on palpebral

conjunctivae, the dorsa of the hands and feet, the anterior chest and abdominal walls, the oral mucosa, and the soft palate.

– Subungual (splinter) hemorrhages - Dark red linear lesions in the nailbeds that do not extend for entire length of nails

– Roth spots - Retinal hemorrhages with small, clear centers; rare and observed in only 5% of patients

– Janeway lesions - irregular erythematosus and painless macules (1-4 mm in diameter). They most often are located on the thenar and hypothenar eminences of the hands and feet.

– Osler nodes – Tender subcutaneous nodules in pulp spaces of the terminal phalanges of the fingers and toes, soles of the feet, and the thenar and hypothenar eminences of the hands. Their appearance is often preceded by neuropathic pain. They last from hours to several days. They remain tender for a maximum of 2 days.

Janeway Lesions

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

Splinter Hemorrhages

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

Subconjuctival Hemorrhages

Septic Retinal Embolus

Roth’s Spots

Osler’s Nodes

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

• Signs of neurologic disease occur in as many as 40% of patients due to embolic stroke with focal neurologic deficits, intracerebral hemorrhage and multiple microabscesses.

• Signs of pulmonary and systemic septic emboli• Signs of congestive heart failure, such as

distended neck veins• Splenomegaly may be present.

• Other signs include the following:– Stiff Neck– Delirium– Paralysis– Hemiparesis– Aphasia– Conjunctival Hemorrhage– Cardiac Arrhythmia

DIAGNOSIS

• Blood cultures• Echocardiograhy• ECG

– Rarely diagnostic– Look for evidence of ischemia, conduction delay,

and arrhythmias• Clinical criteria

• Because symptoms and signs are nonspecific, vary greatly, and may develop insidiously, diagnosis requires a high index of suspicion.

• Endocarditis should be suspected in patients with fever and no obvious source of infection, particularly if a heart murmur is present.

• Suspicion of endocarditis should be very high if blood cultures are positive in patients who have a history of a heart valve disorder, who have had certain recent invasive procedures, or who abuse IV drugs.

• Patients with documented bacteremia should be examined thoroughly and repeatedly for new valvular murmurs and signs of emboli.

Blood Culture• If endocarditis is suspected, 3 blood cultures (20 mL each)

should be obtained within 24 h (if presentation suggests ABE, 2 cultures within the first 1 to 2 h).

• When endocarditis is present and no prior antibiotic therapy was given, all 3 blood cultures usually are positive because the bacteremia is continuous; at least 1 culture is positive in 99%.

• Premature use of empiric antibiotic therapy should be avoided in patients with acquired or congenital valvular or shunt lesions to avoid culture-negative endocarditis.

• If prior antimicrobial therapy was given, blood cultures should still be obtained, but they may be negative.

• Established infections often cause a normocytic-normochromic anemia, elevated WBC count, increased ESR, increased Igs, circulating immune complexes, and rheumatoid factor, but these findings are not diagnostically helpful.

• Urinalysis often shows microscopic hematuria and, occasionally, RBC casts, pyuria, or bacteriuria.

Echocardiography

• Transthoracic 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

Diagnosis

• Definitive diagnosis of infective endocarditis (IE) is generally made by using the Duke criteria.

• Durack and colleagues developed diagnostic criteria in 1994 that combine the – clinical, – microbiological, – Pathological,– echocardiographic characteristics of a specific case.

• Definitive Endocarditis– Two major or,– One major and three minor or,– five minor

• Possible Endocarditis – One major and one minor or, – Three minor

• Rejection criteria

Modified Dukes Criteria for diagnosis of Infective Endocarditis

• Major blood culture criteria include the following:– Two blood cultures positive for organisms typically found in

patients with IE (S viridans, Streptococcus bovis, a HACEK group organism, community-acquired S aureus, or enterococci in the absence of a primary focus)

– Blood cultures persistently positive for one of the above organisms from cultures drawn more than 12 hours apart

– Three or more separate blood cultures drawn at least 1 hour apart, positive for organisms consistent with IE

• Major echocardiographic criteria include the following:– Echocardiogram positive for IE, documented by an

oscillating intracardiac mass on a valve or on supporting structures in the path of regurgitant jets, or on implanted material in the absence of an alternative anatomical explanation

– Myocardial abscess– Development of partial dehiscence of a prosthetic valve– New-onset valvular regurgitation

• Minor criteria include the following:– Predisposing heart condition or intravenous drug use– Fever of 38°C (100.4°F) or higher– Vascular phenomenon, including major arterial emboli, septic

pulmonary infarcts, intracranial hemorrhage, conjunctival hemorrhage, or Janeway lesions

– Immunological phenomenon such as glomerulonephritis, Osler nodes, Roth spots, and rheumatoid factor

– Positive blood culture results not meeting major criteria or serologic evidence of active infection with an organism consistent with IE (Brucella, C burnetii [Q fever], Legionella)

– Rheumatoid factor– Echocardiogram results consistent with IE but not meeting major

echocardiographic criteria

• Rejection criteria for the diagnosis of IE are as follows:– The presence of a firm alternative diagnosis of the

manifestations of endocarditis– Resolution of manifestations of endocarditis after

4 or fewer days of antimicrobial therapy– No pathologic evidence of IE at surgery or autopsy

after 4 or fewer days of antimicrobial therapy

DIFFERENTIALS

• Antiphospholipid syndrome• Primary cardiac neoplasms• Endocarditis • Systemic lupus erythematosus• Reactive arthritis

TREATMENT

• The major goals of therapy for infective endocarditis (IE) are to – eradicate the infectious agent from the thrombus– address the complications of valvular infection.

• General measures include the following:– Treatment of congestive heart failure– Oxygen– Hemodialysis (may be required in patients with

renal failure)

• Antibiotics remain the mainstay of treatment for IE.

• In acute IE, institute antibiotic therapy as soon as possible to minimize valvular damage.

• In subacute IE, treatment may be safely delayed until culture and sensitivity results are available.

• Initial antibiotic choice is empiric in nature, determined by clinical history and physical examination findings.

• High dose antibiotics are administered by the intravenous route to maximize diffusion of antibiotic molecules into vegetation(s) from the blood filling the chambers of the heart.

• This is necessary because neither the heart valves nor the vegetations adherent to them are supplied by blood vessels.

• Antibiotics are continued for a long time, typically two to eight weeks.

• Bactericidal antibiotics are considered necessary for cure of valvular infection.

• Orally administered antibiotics have been used as suppressive therapy for incurable valvular infections (inoperable PVE).

• Treat all patients in a hospital or skilled nursing facility to allow adequate monitoring of the development of complications and the response to antibiotic therapy.

• The American Heart Association (AHA) has developed guidelines for treating IE caused by the most frequently encountered microorganisms.

• Adult NVE caused by penicillin-susceptible S viridans, S bovis, and other streptococci– Penicillin G at 12-18 million U/d IV by continuous pump or in 6 equally

divided doses for 4 weeks– Ceftriaxone at 2 g/d IV for 4 weeks or IM for short periods .ceftriaxone

allows once-a-day outpatient IV therapy for clinically stable patients. – Penicillin G and gentamicin at 1 mg/kg every 8 hours for 2 weeks;

short-course therapy with ceftriaxone and gentamicin for 2 weeks in uncomplicated NVE caused by sensitive S viridans and of less than 3 months’ duration

– Vancomycin at 30 mg/kg/d IV in 2 equally divided doses for 4 weeks; the vancomycin dose should not exceed 2 g/d

• NVE caused by relatively penicillin resistant streptococci – Penicillin G at 18 million U/d IV, either by continuous

pump or in 6 equally divided doses, for 4 weeks– Cefazolin at 6 g/d IV in 3 equally divided doses for 4 weeks– Both of the above regimens are combined with gentamicin

at 1 mg/kg IM or IV every 8 hours for the first 2 weeks of therapy

– Vancomycin at 30 mg/kg/d IV in 2 equally divided doses for 4 weeks

• IE caused by nonresistant enterococci, resistant S viridans or nutritionally variant S viridans

• PVE caused by penicillin-G–susceptible S viridans or S bovis should be treated as follows:– Penicillin G at 18-30 million U/d IV, either by continuous pump or

in 6 equally divided doses daily, combined with gentamicin at 1 mg/kg IM or IV every 8 hours for 4-6 weeks

– Ampicillin at 12 g/d by continuous infusion or in 6 equally divided doses daily, combined with gentamicin at 1 mg/kg IM or IV every 8 hours for 4-6 weeks

– Vancomycin at 30 mg/kg/d in 2 equally divided doses. This may be combined with gentamicin for 4-6 weeks.

• NVE caused by methicillin-sensitive S aureus (MSSA) should be treated as follows:– nafcillin or oxacillin at 2 g IV every 4 hours for 4-6

weeks– cefazolin at 2 g IV every 8 hours for 4-6 weeks– vancomycin at 30 mg/kg for 4-6 weeks

• P aeruginosa– Cefepime, or imipenem, combined with high-dose tobramycin at 8

mg/kg/d in 3 divided doses for 6 weeks • Enteric gram-negative rods (E coli, Proteus mirabilis)

– Ampicillin, ceftriaxone, or cefepime combined with gentamicin for 4-6 weeks

• Streptococcus pneumoniae– Ceftriaxone at 2 g/d IV or vancomycin for 4 weeks

• Diphtheroids– Penicillin G at 18-24 million U/d in 6 divided doses or vancomycin

combined with gentamicin for 4 weeks • Q fever (C burnetii infection)

– Doxycycline combined with rifampin, for 3-4 years

• Anticoagulation is controversial. • Evidence indicates patients who are anticoagulated

have worse outcomes than those who are not anticoagulated.

• Patients who are treated with anticoagulation appear to have a higher rate of intracerebral bleeding.

• If an established reason for anticoagulation (deep venous thrombosis) exists, a standard regimen of anticoagulation should be followed.

Indications for surgery

• Congestive heart failure refractory to standard medical therapy

• Fungal IE (except that caused by Histoplasma capsulatum)

• Persistent sepsis after 72 hours of appropriate antibiotic treatment

• Recurrent septic emboli, especially after 2 weeks of antibiotic treatment

• Rupture of an aneurysm of the sinus of Valsalva• Conduction disturbances caused by a septal abscess

• A second relapse, during or after completion of treatment, requires replacement of the valve.

• Paravalvular abscess and intracardiac fistula • Patients with culture-negative NVE who remain

febrile for more than 10 days. • Persistent hypermobile vegetations • Patients with multi-resistant organisms (enterococci)• Metastatic infections (macroabscesses of the brain

and spleen)

Monitoring

• Blood cultures taken after 3-4 days of treatment to document eradication of the bacteremia.

• Blood cultures during treatment are essential if persistent fever or other signs develop that suggest failing treatment.

• Failure to sterilize the bloodstream should prompt a search for metastatic infection (abscesses, especially splenic, or mycotic aneurysm).

• Fever lasting longer than 10 days into therapy should prompt a search for suppurative complications.

• Approximately 30% of patients have a return of fever after the initial response. This is usually caused by an intracardiac abscess or metastatic infection.

• Causes of unresponsive fever include myocardial or septal abscesses, large vegetations that resist sterilization, and metastatic infection.

• Patients with staphylococcal endocarditis tend to respond more slowly.

• Diminution of vegetation size can be followed by serial echocardiography

COMPLICATIONS

• Valvular dysfunction, usually insufficiency of the mitral or aortic valves

• Myocardial or septal abscesses• Congestive heart failure• Metastatic infection• Embolic phenomenon• Organ dysfunction resulting from immunological

processes• Relapse

Recurrence• Relapse of IE usually occurs within 2 months of finishing clinically

effective therapy. – Infection with S aureus, enterococci, and gram-negative organisms

(especially P aeruginosa) is associated with a high rate of relapse. – Enterococcal infection of the mitral valve has the greatest potential for

relapse.– Recurrent IE occurs most often in individuals who abuse IV drugs. – Valvular infections in these patients recur at a rate of 40%. – Those with pretreatment symptoms of IE of more than 3 months’

duration are at greater risk for relapse. • Other significant risk factors for recurrence include a previous

episode of IE, the presence of a prosthetic valve, and congenital heart disease.

PREVENTION

• Preventive dental examination and therapy before surgery to repair heart valves or congenital heart lesions is recommended.

• The American Heart Association (AHA) recommends antimicrobial prophylaxis for patients at high risk of an adverse outcome from infective endocarditis.

Such patients include those with• Prosthetic heart valves• Previous infective endocarditis• Congenital heart diseases (CHD):

– Unrepaired cyanotic CHD (including palliative shunts and conduits),

– completely repaired CHD during the 1st 6 months after surgery if prosthetic material or device was used

– repaired CHD that has residual defects at or adjacent to the site of repair

• Heart transplant recipients with valvulopathy

• Any procedure involving manipulation of gingival tissue or the periapical region of teeth, or perforation of the oral mucosa

• Any procedure involving incision in the respiratory mucosa

• Procedures on infected skin or musculoskeletal tissue including incision and drainage of an abscess

• Prophylaxis is no longer routinely recommended for gastrointestinal or genitourinary procedures.

ROUTE DRUGS AND DOSAGE IN ADULTS (AND CHILDREN)

DRUGS AND DOSAGE IN ADULTS (AND CHILDREN) ALLERGIC TO PENICILLIN

ORAL (GIVEN 1 HOUR BEFORE PROCEDURE)

AMOXYCILLIN 2g (50mg/kg) PO CLINDAMYCIN 600mg (20mg/kg) PO or

CEPHALEXIN 2g (50mg/kg) or

AZITHROMYCIN or CLARITHROMYCIN 500mg (15mg/kg) PO

PARENTERAL (GIVEN 30 MINS BEFORE PROCEDURE)

AMPICILLIN 2g (50mg/kg) IM/IV CLINDAMYCIN 600mg (20mg/kg) IV or

CEFAZOLIN 1g (25mg/kg) IM/IV

PROGNOSIS• In contemporary population-based studies of infective

endocarditis in industrialized countries, in-hospital mortality ranges from 15 to 22% and 5-year mortality is approximately 40%.

• In-hospital mortality is less than 10% among patients with right-sided lesions or oral streptococcal, left-sided, native-valve lesions, whereas it is 40% or more among patients with prosthetic-valve infective endocarditis due to Staphylococcus aureus.

• Independent predictors of mortality included higher age, S. aureus infection, heart failure, cerebrovascular and embolic events.

• THANKS FOR LISTENING

REFERENCES • International journal of general medicine, march 2013.• Bode-Thomas F, Ige O.O, Yilgwan C. Childhood acquired heart

diseases in Jos, north central Nigeria. Niger Med J 2013• National center for biotechnology information journal, 2007• New England Journal of Medicine. Bruno Hoen, M.D., Ph.D.,

and Xavier Duval, M.D., Ph.D. April, 2013• Mitchell RS, Kumar V, Robbins SL, Abbas AK, Fausto N (2007).

Robbins Basic Pathology (8th ed.). • Kasper DL, Brunwald E, Fauci AS, Hauser S, Longo DL, Jameson

JL (May 2005). Harrison's Principles of Internal Medicine.