Infective Endocarditis

Amonthep Waipara

Endocarditis• An inflammation of the endocardium,

Which is the membranes lining the chamberof the heart and covering the cusps of the heart valves.

Endocarditis• Infection of the heart valves by

various microorganisms.• Average motality is 20%• Classified by clinical presentation:–Acute bacterial endocarditis (ABC)–Subacute bacterial endocarditis

(SBC)

Infection

ABE SBE

Symptoms Fulminating, high fever,

WBC systemic toxicity

Indolent, fatigue,

weakness,low grade

fever, wt lossValves

involved native Preexisting

valvular heart disease or prosthetic

Caused S.aureus (virulent)

Streptococcus pyogens,

s.pneumoiae

Viridans strep (less invasive),

Staphylococcus

epidermidisUntreated Death to < 6

wkDeath 6 wk-3

mo

Problem associated with this classification

• Overlap clinical presentation and the course of disease

• Ignore many nonbacterial causes of endocarditis: chlamydiae, rickettsiae, and fungi

Classification of IE

Native-valve IE• Congenital

heart disease• Rheumatic

heart disease• Degenerative

valve lesion

Posthetic valve IE

• Eaely (w/n 60 day after Sx)

• Late (after 60 day of Sx)

IE in IVDU Nosocomial IE

Posthetic – valve EndocarditisEaely infection

• S. epidermidis• S. aureus

Late infection

• Streptococci• HACEK

IE in IVDU

• Occurs in young people (30-40 years old)• Valve affected:– Tricuspid (>50%) > Aortic (25%) > Mitral (20%)

• HIV-infected : 4-fold increased risk in CD4 < 200 cell/mcl

• Etiology:– S.aureus, P. aeruginosa, fungi– HIV pts: bartonella, salmonella,Listeria

Nosocomial IE

• About 22% pts with IE• Etiology:– S.aureus, enterococci

• Frequently associated with – Catheters or medicosurgical procedures

• Mortality rate: >50%

Pathogenesis Damaged endothelial surface of the heart

Deposition of platelets and fibrin on the surface

Nonbacterial Thrombotic Endocarditis (NBTE)

Bacteria adheres to damaged valve completeted w/n minutes during transient bacteremia

A vegetation of fibrin, platelets, and bacteria form

Site of Involvement

• Determined by the underlying cardiac defect and the infecting organisms.– Mitral valve : VS (85%)– Tricuspid value : Staphylococci and IVDU– Mitral > Aortic > Tricuspid> pulmonic valves

Complications

• Cardiac complications– Heart failure

• Neurologic complications– Ischemic stroke– Intracranial hemorrhage – S.aureus

• splenomegaly

Risk factors

• โรคลิ้��นหัวใจผิ�ดปกติ�• การใส่�ลิ้��นหัวใจเที�ยม• Previous IE• ม�หัวใจผิ�ดปกติ�มาติ�งแติ�ก�าเน�ด• คนที��เป�นโรคหัวใจร�มาติ�ก (rheumatic heart disease)• Hypertrophic cardiomyophathy• Mitral valve prolapsed with regurgitation• พวกที��ที�า Hemodialysis หัร!อพวกที��ม�การน�าเลิ้!อดเข้$าออก

จากร�างกาย• IVDU

Etiologic Organisms IE

• Streptococci 55-62• Viridans streptococci 30-40• Other streptococci 15-25

• Enterococci 5-18• Staphylococci 20-35

• Coagulase positive 10-27• Coagulase negative 1-3

• Gram –ve aerobic bacteria 1.5-13• Fungi 2-4• Miscellaneous bacteria <5• Mixed infection 1-2• Culture negative< 5-24

ส่าเหัติ% native-valve แลิ้ะ prosthetic-valve endocarditis

Incidence(%) of bact.

• Dental มกจะพบติรงน��เป�นส่�วนมาก• การถอนฟั+น 18-85• การผิ�าฟั+น 32-88• การเค��ยวลิ้�กอม 17-51• การแปรฟั+น 0-26• การใส่�พวกอ%ปกรณ์-ที�าฟั+น 27-50

• Upper airway• การที�า bronchoscopy 15• การผิ�าทีอนซิ�ลิ้ 28-38• การที�า suction 16

Objective findings of IE(%)

Fever 90Splenomegaly 20-57Mycotic aneurysm 20Clubbing 12-

52Retinal lesion 2-10Sign of Renal

Failure 10-15

Heart murmur 85Changing murmur 5-

10New murmur 3-5Embolic phenomenon >50Skin manifestation 18-50

• Osler node• Splinter hemorrhages • Petechiae• Janeway lesion

Splinter hemorrhages

Osler node

PetechiaeJaneway lesion

Laboratory Finding

Lab ABE SBE

WBC Elevated Elevated

ESR Elevated Elevated

Other Normocytic, normochromic anemia, low SFe

Blood Cultures

• Hallmark “Continuous bacteremia”, caused by bacteria shedding from the vegetation into the blood stream.

• 3 set, each from separate site, should be collected over 24 hr.

Blood Cultures

• +ve result: 95% of bacterial endocarditis50% of fungal endocarditis

• False negative: – Prior antibiotics (culture-negative endocarditis)-

suppress pathogen’s growth– Fastidious organisms

Echocardiography

• To identify and localize valvular lesions• Transthoracic Echocardiography (TTE)– Sensitivity 60-65%

• Transesophageal Echocardiography (TEE)– Sensitivity 95%– Use when – ve blood cultures– Recommended in pts:

• With prosthetic valves• Rated as possible IE by clinical criteria• With complicated IE (paravalvular abscess)

Echocardiographic finding

• + ve result :– A large vegetation (>1cm), a ring abscess, or

intracardiac fistula– Alert for monitoring complications: septic emboli

and HF• - ve result– Does not exclude endocarditis

Diagnosis

• Signs and symptoms : nonspecific• Lab: nonreliable• Diagnostic criteria: Duke criteria• Blood culture: identify infecting pathogens• TEE: determine the presence of valvular

vegetation

Treatment

• Desired outcome– Relieve the S&S of the disease– Eradicate the causative organism with minimal drug

exposure– Provide cost-effective abx therapy, determined by:

• The likely or identified pathogen• Drug susceptibilities• Hepatic and renal function• Drug allergies• Anticipated drug toxicities

To eradicate causative organism

• High-dose IV (bactericidal) antibiotics– Serum concentration > Minimal Bactericidal

concentration(MBC) • The synergistic combination may be needed

for some organisms– To complete more rapid and complete bactericidal

effects– Weigh risk and benefit

Antibiotic UsePCN G DOC for streptococciNaf- / Oxa- / cloxacillin

DOC for staphylococci

Ampicillin DOC for enterococciGentamicin Synergitic effect for

enterococci hhasten the pace of cure (strep & staphy)Prevent emergence of resistant org(PVE caused by coagulase –ve staphy)

Vancomycin Reserved for resistant orgs and pts with immediate B-lactam allergies

Nonpharmacologic Treatment

• Valve replacement surgery:– Large vegetation (> 10mm)– >1 embolic event during 1st 2 wk of tx– Severe valvular insufficiency– Valvular perforation or dehiscence– Decompensated heart faliure, perivalvular or

myocardial abscess– New heart block– Persistent fever or bactermia

Viridans streptococci

• The most etiologic agents in SBE (native valves) and non injection drug users.

• A large number of different species– Streptococcus sanguis– Streptococcus oralis (mitis)– Streptococcus salivarius– Streptococcus mutans– other

Tx of Native Valve Endocarditis due to Highly PCN-S-Viridans streptococci & S. bovis(MIC <0.12 mcg/mL)

Antibiotic Dosage ,Route Duration

Aq. PCN G Naorceftriaxone

12-18 mU/d IV 4 wk

2 g once daily IV/IM 4 wk

Aq. PCN G Na+gentamicin

12-18 mU/d IV 2 wk

3 mg/kg IM/IV od 2 wk (Pk 3; Tr<1)

Ceftriaxone +gentamicin

2 g IV/IM od 2 wk

3 mg/kg IM/IV od 2 wk(Pk 3; Tr<1)

Vancomycin HCl (for pt all to B-lactams)

15 mg/kg (not 2 g/d) IV q 12(infused > 1 hr)

4 wk(Pk 30-45)

Tx of Native Valve Endocarditis due to Highly PCN-Relatively-R-

Viridans Streptococci & S. bovis(MIC >0.12,< 0.5 mcg/mL) Antibiotic Dosage ,Route Duration

Aq. PCN G Na+gentamicin

24 mU/d IV 4 wk

3 mg/kg IM/IV od 2 wk (Pk 3; Tr<1)

Ceftriaxone +gentamicin

2 g IV/IM od 4 wk

3 mg/kg IM/IV od 2 wk(Pk 3; Tr<1)

Vancomycin HCl (for pt all to B-lactams)

15 mg/kg (not 2 g/d) IV q 12(infused > 1 hr)

4 wk(Pk 30-45)

Antibiotic Dosage ,Route DurationAq. PCN G Na+gentamicin

18-30 mU/d IV (q4) 4-6 wk

1 mg/kg IM/IV q8 4-6 wk (Pk 3; Tr<1)

Ampicillin Na+gentamicin

12 g/d IV (2g q4) 4-6 wk

1 mg/kg IM/IV q8 4-6 wk Pk 3; Tr<1)

Vancomycin HCl (for pt all to B-lactams)+gentamicin

15 mg/kg (not >2 g/d) IV q 12

4-6 wk (Pk 30-45)

1 mg/kg IM/IV q8 4-6 wk(Pk 3; Tr<1)

Tx for Endocarditis due to PCN/Gent/Van-S-Enterococci

• This table is also for VS with MIC of> 0.5 mcg/mL, Abiotrophia defcetiva and Granulicatella spp, or prosthetic valve endocarditis caused by VS or S. bovis

Tx for Endocarditis due to PCN/Van-S, Gent-R-Enterococci

• This table is also for VS with MIC of> 0.5 mcg/mL, Abiotrophia defcetiva and Granulicatella spp, or prosthetic valve endocarditis caused by VS or S. bovis

Antibiotic Dosage ,Route DurationAq. PCN G Na+streptomycin

24 mU/d IV (q4) 4-6 wk

7.5 mg/kg IM/IV q12 4-6 wk

Ampicillin Na+streptomycin

12 g/d IV (2g q4) 4-6 wk

7.5 mg/kg IM/IV q12 4-6 wk

Vancomycin HCl (for pt all to B-lactams)+streptomycin

15 mg/kg (not >2 g/d) IV q 12

6 wk (Pk 30-45)

7.5 mg/kg IM/IV q12 6 wk

Tx for Endocarditis due to AMG/Van-S, PCN-R-Enterococci

Antibiotic Dosage ,Route DurationAmpicillin Na+gentamicin

3 g IV q 6 6 wk

1 mg/kg IM/IV q8 6 wk

Vancomycin HCl (for pt all to B-lactams)+gentamicin

15 mg/kg (not >2 g/d) IV q 12

6 wk

1 mg/kg IM/IV q8 6 wk

Tx for Endocarditis due to AMG/Van/PCN-R-Enterococci

Antibiotic Dosage ,Route DurationE. faeciumLinezolid 600 mg PO/IV q12 > 8wkE. faecalisImipenam +Ampicillin Na

500 mg IV q 6 > 8wk2 g IV q 4 > 8wk

Ceftriaxone +Ampicillin Na

2 g IV/IM q 12 > 8wk

2 g IV q 4 > 8wk

Staphylococci

• S. aureus – IVDU (60-90% of cases), prosthetic heart valve– Does not require a cardiac defect to be infective – More acute onset– Require immediate abx Tx

• S. epidermidis – Prothetic heart valve– Mostly MRSE

Tx of Native Valve Endocarditis due to Staphylococcus

Antibiotic Dosage ,Route DurationMethicillin-Susceptible- Staphylococcus

For non B-lactam – allergic patient

Cloxacillin+gentamicin

2 g IV q 4 6 wk

1 mg/kg IM/IV q 8 3-5 d

For penicillin-allergic pts (nonanaphy lactoid type)

Cefazolin + gentamicinVancomycin

2 g IV q 8 6 wk

1 mg/kg IM/IV q 8 3-5 d

15 mg/kg IV q 12 6 wk

Methicillin-Resistant- Staphylococcus

Vancomycin HClDaptomycin

15 mg/kg IV q 12 6 wk

6 mg/kg IV od 6 wk

IVDU

• Cloxacillin 2 g IV q 4 h + Amikacin 7.5 mg/kg IV q 12 h

• 2 week

Tx of Prosthetic Valve Endocarditis due to Staphylococcus

Antibiotic Dosage ,Route DurationMethicillin-Susceptible- Staphylococcus

CloxacillinRifampicin+gentamicin

2 g IV q 4 > 6 wk

300 mg IV/PO q 8 > 6 wk

1 mg/kg IM/IV q 8 2 wk

Methicillin-Resistant- Staphylococcus

Vancomycin HClRifampicin+gentamicin

15 mg/kg IV q 12 > 6 wk

300 mg IV/PO q 8 > 6 wk

1 mg/kg IM/IV q 8 2 wk

Prosthetic Valve Endocarditis

• Early– Occurs up to 1 yr after surgery– Caused by skin organisms which were implanted

at the time of surgery– SE(30%) > SA, gr-ve bacilli (10-20%)

• Late – Infection of the valve leaflet– Caused by same organism that are responsible for

native valve endocarditis

HACEK Group

• Haemophilus parainfluenzae, Haemophilus aphrophilus

• Actinobacillus actinomycetamcomitans• Cardiobacterium hominis• Eikenella corrodens• Kingella kingae

Tx for Endocarditis due to HACEKAntibiotic Dosage ,Route Duration

Ceftriaxone 2 g once daily IV/IM 4 wk

Ampi/sulbactam 12 g/d IV (3g q6) 4 wk

ciprofloxacin 500 mg PO q 12 4 wk

400 mg IV q 12

Culture-nagtive endocarditis

• Cause:– Prior administration of Abx– Presence of slow-growing and fastidious org:

HACEK, Brucella, Coxiella, Chlamydiae, anaerobes, fungi

• Save blood culture for 3 wks to detect organism

Culture-nagtive endocarditis

• Treatment– if hemodynamic unstable, start empiric abx

covering staphy and gr-ve bacilli, + antifungal agent

– If hemodynamic stable, withhold abx until culture become positive

Endocarditis in HIV-seropositive pts

• Should not be given short – course regimens

Fungal Endocarditis

• A life-threatening infection• Caused by Canndida and aspergillus sp.• Occurs primarily in:– IVDU– Patients with prosthetic heart valve– Immunocompromised pts– Those with IV catheters– Individual receiving broad-spectrum antibiotics

Management of fungal endocarditis

• Early valve replacement • Aggressive fungicidal therapy– Amphotericin B 0.5-1 mg/kg/d IV (total 1.5-3

gm)for > 6 wks– Toxicities from above regimen: nephrotoxicity– Alternative : Fluconazole –safer, active againt

some Candida sp.• D/C broad spectrum Abx, if unnecessary

Indications for Surgery

• Valve dysfunction with HF, perivalvular necrosis, aortic dissection, or valve orifice obstruction

• Persistent bacteremia or other evidence of failure despite appropiate abx Tx

• Most cases of early PVE• Endocarditis caused by resistant organisms

(Enterobacteriaceae, Pseudomonas, or fungi)• Local suppurative complication: myocardial

abscess, etc

Monitoring during Tx

• Efficacy– Blood Cx,temp

• Safety – Depends on Abx

Prevention

• Desired outcomes– Prevent IE in high-risk patients with appropriate

prohylactic antimicrobials

Prophylactic Regimens for Dental Procedures Single dose regimen 30-60 min before procedure

Standard prophylaxis Amoxicillin PO A: 2 g, C: 50mg/kg

Unable to take PO Ampicillin IM/IV A: 2 g, C: 50mg/kg

Cefazolin/Ceftriaxone IM/IV A: 1 g, C: 50mg/kg

PCN-allergy Cephalexin PO A: 2 g, C: 50mg/kg

Clindamycin PO A: 600 mg, C: 20mg/kg

Azithromycin/Clarithromycin PO

A: 500 mg, C: 15 mg/kg

PCN-allergy and unable to take PO

Clindamycin IM/IV A: 600 mg, C: 20mg/kg

Cefazolin/Ceftriaxone IM/IV A: 1 g, C: 50mg/kg

Respiratory procedures that need IE prophylaxis

• Incision or biopsy of the respiratory mucosa– Tonsillectomy– Adenoidectomy– Drainge of abscess or empyema

IE prophylaxis

• Is reasonable for procedures on respiratory tract or infected skin, skin structures, or musculoskeletal tissue only for patient with underlying cardiac conditions associated with the highest risk of adverse outcome from IE

• Is not recommend for GU or GI tract procedures