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
Symptoms

ABE
Fulminating, high fever, WBC systemic toxicity

SBE

Valves involved Caused

Untreated

Indolent, fatigue, weakness,low grade fever, wt loss native Preexisting valvular heart disease or prosthetic S.aureus (virulent) Viridans strep (less Streptococcus pyogens, invasive), s.pneumoiae Staphylococcus epidermidis Death to < 6 wk Death 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 Posthetic valve IE Eaely (w/n 60 Congenital day after Sx) heart disease Late (after 60 Rheumatic day of Sx) heart disease Degenerative valve lesion IE in IVDU Nosocomial IE

Posthetic valve Endocarditis

Eaely 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
Previous IE (rheumatic heart disease) Hypertrophic cardiomyophathy Mitral valve prolapsed with regurgitation Hemodialysis IVDU

Etiologic Organisms IE
Streptococci
Viridans streptococci Other streptococci

55-62
30-40 15-25

Enterococci Staphylococci
Coagulase positive Coagulase negative

5-18 20-35
10-27 1-3

Gram ve aerobic bacteria Fungi Miscellaneous bacteria Mixed infection Culture negative

1.5-13 2-4 <5 1-2 < 5-24

 native-valve prosthetic-valve endocarditis

Incidence(%) of bact.
Dental
18-85 32-88 17-51 0-26 27-50
15 28-38 16

Upper airway
bronchoscopy suction

Objective findings of IE(%)

Fever 90 Splenomegaly 20-57 Mycotic aneurysm 20 Clubbing 12-52 Retinal lesion 2-10 Sign of Renal
Failure 10-15

Heart murmur 85 Changing murmur 5-10 New murmur 3-5 Embolic phenomenon >50 Skin manifestation 18-50
Osler node Splinter hemorrhages Petechiae Janeway lesion

Osler node

Splinter hemorrhages

Janeway lesion

Petechiae

Laboratory Finding
Lab WBC ESR Other ABE Elevated Elevated SBE Elevated Elevated 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 endocarditis 50% of fungal endocarditis False negative:
Prior antibiotics (culture-negative endocarditis)suppress pathogens 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
PCN G Naf- / Oxa- / cloxacillin Ampicillin Gentamicin

Use
DOC for streptococci DOC for staphylococci DOC for enterococci Synergitic effect for enterococci hhasten the pace of cure (strep & staphy) Prevent emergence of resistant org(PVE caused by coagulase ve staphy) Reserved for resistant orgs and pts with immediate B-lactam allergies

Vancomycin

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-SViridans streptococci & S. bovis(MIC <0.12 mcg/mL)
Antibiotic Aq. PCN G Na or ceftriaxone Aq. PCN G Na +gentamicin Ceftriaxone +gentamicin Dosage ,Route 12-18 mU/d IV 2 g once daily IV/IM 12-18 mU/d IV Duration 4 wk 4 wk 2 wk 2 wk (Pk 3; Tr<1) 2 wk 2 wk(Pk 3; Tr<1) 4 wk(Pk 30-45)

3 mg/kg IM/IV od
2 g IV/IM od

3 mg/kg IM/IV od Vancomycin HCl (for pt 15 mg/kg (not 2 g/d) all to B-lactams) IV q 12(infused > 1 hr)

Tx of Native Valve Endocarditis due to Highly PCN-RelativelyR-Viridans Streptococci & S. bovis(MIC >0.12,< 0.5 mcg/mL)
Antibiotic Aq. PCN G Na +gentamicin Dosage ,Route 24 mU/d IV Duration 4 wk

3 mg/kg IM/IV od
Ceftriaxone +gentamicin 2 g IV/IM od 3 mg/kg IM/IV od Vancomycin HCl (for pt all to B-lactams) 15 mg/kg (not 2 g/d) IV q 12(infused > 1 hr)

2 wk (Pk 3; Tr<1)
4 wk 2 wk(Pk 3; Tr<1) 4 wk(Pk 30-45)

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

Antibiotic Aq. PCN G Na +gentamicin Ampicillin Na +gentamicin Vancomycin HCl (for pt all to B-lactams) +gentamicin Dosage ,Route 18-30 mU/d IV (q4) 1 mg/kg IM/IV q8 12 g/d IV (2g q4) 1 mg/kg IM/IV q8 Duration 4-6 wk 4-6 wk (Pk 3; Tr<1) 4-6 wk 4-6 wk Pk 3; Tr<1)

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)

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-REnterococci

Antibiotic Aq. PCN G Na +streptomycin Ampicillin Na +streptomycin Vancomycin HCl (for pt all to B-lactams) +streptomycin Dosage ,Route 24 mU/d IV (q4) 7.5 mg/kg IM/IV q12 12 g/d IV (2g q4) 7.5 mg/kg IM/IV q12 Duration 4-6 wk 4-6 wk 4-6 wk 4-6 wk

15 mg/kg (not >2 g/d) IV q 12 6 wk (Pk 30-45)

7.5 mg/kg IM/IV q12

6 wk

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 AMG/Van-S, PCN-REnterococci

Antibiotic Ampicillin Na +gentamicin Vancomycin HCl (for pt all to B-lactams) +gentamicin Dosage ,Route 3 g IV q 6 1 mg/kg IM/IV q8 Duration 6 wk 6 wk

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 E. faecium Linezolid E. faecalis Imipenam + Ampicillin Na Ceftriaxone + Ampicillin Na Dosage ,Route Duration

600 mg PO/IV q12

500 mg IV q 6 2 g IV q 4 2 g IV/IM q 12 2 g IV q 4

> 8wk
> 8wk > 8wk > 8wk > 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 Duration Methicillin-Susceptible- Staphylococcus For non B-lactam allergic patient Cloxacillin +gentamicin 2 g IV q 4 1 mg/kg IM/IV q 8 6 wk 3-5 d

For penicillin-allergic pts (nonanaphy lactoid type) Cefazolin + gentamicin Vancomycin 2 g IV q 8 6 wk

1 mg/kg IM/IV q 8
15 mg/kg IV q 12

3-5 d
6 wk

Methicillin-Resistant- Staphylococcus Vancomycin HCl Daptomycin 15 mg/kg IV q 12 6 mg/kg IV od 6 wk 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 Cloxacillin Rifampicin +gentamicin Dosage ,Route 2 g IV q 4 300 mg IV/PO q 8 1 mg/kg IM/IV q 8 Methicillin-Resistant- Staphylococcus Vancomycin HCl Rifampicin +gentamicin 15 mg/kg IV q 12 > 6 wk Duration > 6 wk > 6 wk 2 wk Methicillin-Susceptible- Staphylococcus

300 mg IV/PO q 8
1 mg/kg IM/IV q 8

> 6 wk
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 HACEK

Antibiotic Ceftriaxone Ampi/sulbactam ciprofloxacin Dosage ,Route 2 g once daily IV/IM 12 g/d IV (3g q6) 500 mg PO q 12 400 mg IV q 12 Duration 4 wk 4 wk 4 wk

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 Unable to take PO Amoxicillin PO Ampicillin IM/IV Cefazolin/Ceftriaxone IM/IV PCN-allergy Cephalexin PO Clindamycin PO Azithromycin/Clarithromyci n PO A: 2 g, C: 50mg/kg A: 2 g, C: 50mg/kg A: 1 g, C: 50mg/kg A: 2 g, C: 50mg/kg A: 600 mg, C: 20mg/kg A: 500 mg, C: 15 mg/kg

PCN-allergy and unable to take PO

Clindamycin IM/IV Cefazolin/Ceftriaxone IM/IV

A: 600 mg, C: 20mg/kg 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