ENDOKARDITIS INFEKTIF

MIOKARDITIS

Masrul Syafri
Bagian Kardiologi dan Kedokteran Vaskular
FKUA/ RS Dr M Jamil Padang
Infective Endocarditis
Definitions

A microbial infection of a cardiac valve or the

endocardium caused by bacteria, fungi, or chlamydia
Often categorized as acute or subacute based on the
rapidity of the clinical course

100% fatal if undiagnosed and untreated

20% fatal if diagnosed and treated
uncommon
primarily in adults
commonly with underlying heart disease
Epidemiology of Endocarditis
Incidence the same or slightly increased
1.7-6.2/100,000 depending on the population
The age of subjects with endocarditis has increased
over the past 60 years (30-40 to 47-69)
Among injecting drug users the incidence is as
high as 150-2000/100,000 person years
There has also been a change in the microbiology of
cases
Increasing incidence of staphylococci
There has been an increasing incidence of nosocomial
endocarditis - both native and prosthetic valve
There is an increased risk of IE among injecting drug
users, patients on long-term hemodialysis, patients with
intravenous catheters, diabetics and HIV-infected
patients
 PVE None
14% 14%
RHD MVP
10% 21%

Acquired
19% CHD
22%
IV drug users and nosocomial cases excluded.

Strom BL, Abrutyn E, Berlin JA, Kinman JL, Feldman RS, Stolley PD, et al.
Ann Intern Med. 1998;129:761-9.
Risk Factors for Infective Endocarditis

Dental procedures, poor dental hygiene - viridans

streptococci, nutritionally variant streptococci, HACEK
Prosthetic valves
Early: coagulase negative staphylococci, S. aureus
Late: coagulase negative staphylococci, viridans
streptococci
Gastrointestinal or genitourinary procedures - enterococci
or S. bovis (colon carcinoma)
Nosocomial - S. aureus (including MRSA), Gram negatives,
Candida species
Brouqui and Raoult, Clin Microbiol Rev, 2001
 Pathogenesis of Infective Endocarditis
Valvular endothelium Mucous membranes - other
peripheral tissue

Congenital abnormalities, Trauma - damage at

turbulent blood flow tissue surface

Nonbacterial thrombus, Transient

Native valves bacteremia

Adherence and colonization

Platelet adherence, fibrin deposition vegetation formation
Elaboration of bacterial enzymes, proteases
Pathogenesis of Endocarditis

Inoculation of bacteria colonizing a mucosal (e.g., oral

mucosa) or peripheral tissue site into the bloodstream
Transient bacteremia of a serum-resistant pathogen
capable of adhering to a cardiac valvular surface
Turbulent blood flow across the valve
Bacterial adherence to cardiac valvular surface
Pathogen - host tissue interaction resulting in vegetation
formation and local tissue damage Bacterial
persistence
Dissemination of infection to other tissue sites and
elicitation of systemic findings
Characteristic lesion vegetation containing :
platelets, erythrocytes, fibrin, inflamatory cells and
microorganisms.
Factors Contributing to the
Pathogenesis of Endocarditis

Hemodynamics - blood flow patterns

Bacterial properties
Host factors
HEMODYNAMICS OF
ENDOCARDITIS
 Host Factors Involved in the
Pathogenesis of Infective Endocarditis
Valvular surfaces
Nonbacterial thrombus forms on damaged valves
Direct adherence to the endovascular surface of
normal valves
Suture line, valve surface of prosthetic valves
Platelets dual role
Platelet microbicidal proteins (-granules)
Bacteria induce platelet aggregation
Part of nonbacterial thrombus surface
Leukocytes, complement, cytokines
 The Pathogenetic Basis for the Clinical
Manifestations of Infective Endocarditis

Valvular destruction and local intracardiac

complications
Bland or septic embolization of vegetations
Sustained bacteremia
Immunologic phenomena

Osler, Gulstonian Lectures, Lancet, 1885

Weinstein and Schlesinger NEJM, 1974
Clinical features
Incubation period - NVE 2 weeks
- PVE 2-5 weeks or more
Signs and symptoms
Symptoms % Signs %
Demam 80-85 % Demam 80-90 %
Menggigil 42-75 % Murmur 80-85 %
Keringat 25 % Changing/new murmur 10-40 %
Anoreksia 25-55 % Abnormalitas syaraf 30-40 %
Penurunan BB 25-35 % Kejadian emboli 20-40 %
Malaise 25-40 % Splenomegali 15-50 %
Dyspnea 20-40 % Clubbing 10-20 %
Batuk 25 % Manifestasi perifer
Stroke 13-20 % Oslers node 7 -10 %
Sakit kepala 15-40 % Splinter haemorrhage 5-15 %
Mual/muntah 15-20 % Petechiae 10-40 %
Myalgia/arthralgia 15-30 % Janeway lesion 6-10 %
Nyeri dada 8-35 % Retinal lesion/Roth spot 4-10 %
Nyeri perut 5-15 %
Nyeri punggung 7-10 %
Confusion 10-20 %

Karchmer AW. Infective endocarditis. In : Braunwald E,editor, Heart Disease.

5th edn Philadelphia:Saunders;1997
 Janeway Lesions: Oslers Nodes:
erythematous, Tender,
macular, non tender. subcutaneous
septic emboli? nodules.
4 Ps:
Pink
Painful
Pea-sized
Pulp of the fingers/toes.

Immunologic origin?
 Subungual (splinter) hemorrhage
Conjunctival hemorrhage
Retinal hemorrhage: Roth Spot
Clinical features

Janeways lesion Splinter haemorrhage

Mylonakis E, Calderwood SB. Infective endocarditis in adults.
NEJM 2001;345:1318-29.
Clinical features

Conjuctival petechiae Oslers node

Mylonakis E, Calderwood SB. Infective endocarditis in adults.

NEJM 2001;345:1318-29.
sxs<60 d post op
 30-65% of native valve endocarditis
Normal oral commensals
A group, composed of several species:
S. mitior, S. sanguis, S. mutans,etc.
Alpha-hemolytic, non-typable
Typical agents of classic SBE

Strep. viridans
 S. bovis
Lancefield group D
Gut flora: associated with GI pathology
S. pneumonia
1-3% of cases of IE with predilection for AV
Usually, in those with immune suppression
DM and Ethanolism
Group B Streptococci
Elderly with chronic disease
 Normal inhabitant of GI tract.
Frequently encountered in UTIs.
Up to 40% of cases without identified
underlying predisposition to IE.
Difficult to treat due to drug resistance.
 Coagulase Positive (Staph. aureus)
a major causative agent in all populations of IE
typically produces acute IE
fulminant, rapidly progressive with few immunologic
signs.
CNS complications in 30-50%
Coagulase Negative (Staph. epi, et al)
Major cause of PVE. 3-8% of NVE.
 Hemophilus, Actinobacillus,
Cardiobacterium, Eikenella, Kingella
Gram negative inhabitants of the upper
airways.
Large vegetations, high likelihood of
embolization.
Slow growing: hold cultures for 3 weeks.
Traditionally sensitive to beta lactams,
now some produce beta lactamase.
 Commonly encountered agents:
Candida, Torulopsis, Aspergillus
Predispositions
Prosthetic valves
IVDA
Immunosupression
Hyperalimentation
Prolonged abx treatment
Large vegetations and frequent embolic
events.
 Pseudomonas
Brucella
Diphtheroids
Listeria
Bartonella
Coxsiella
Chlamydia
 Accounts for 25% of
cases of IE in US. MV
5:1 male:female 24% AV
6%
Pre-existing
valvular diseases
uncommon.
TV
Variable 70%
microbiology.
Mortality<10%.
 Affects 3% of prosthesis patients.
Highest risk in first 6 months post op.
Accounts for 10-20% of all IE cases.
Increased risk in
Males
Blacks
Prolonged pump time
Multiple valve replacement
 Early (<12 months)-Staph epi
late (after 12 months)- mimics NVE
DIAGNOSIS
KRITERIA DUKE
A. Endokarditis infektif definitif :
1. Kriteria patologi
Mikroorganisme : dibuktikan dengan hasil biakan
atau histologi vegetasi atau pada vegetasi yang
mengalami emboli atau pada abses dalam jantung
atau
Lesi patologi : abses dalam jantung dan vegetasi
yang diperjelas oleh histologis yang
memperlihatkan
EI aktif
2. Kriteria klinik :
2 kriteria mayor atau
1 kriteria mayor dan 3 minor atau
5 kriteria minor
DIAGNOSIS

B. Kemungkinan endokarditis infektif (possible)

Hasil sesuai dengan EI tetapi tidak cukup
definitive, maupun rejected

C. Endokarditis infektif ditolak (rejected )

- Terdapat bukti kuat yang menunjang gejala yang
disebabkan penyakit lain
- Perbaikan manifestasi EI dengan pengobatan
antibiotik dalam waktu 4 hari atau kurang
- Tidak ditemukan bukti EI pada operasi atau otopsi
setelah pengobatan antibiotik 4 hari atau kurang

ESC guidelines
Blood cultures critical for specific diagnosis
3 sites 30-60 minutes apart
before starting antibiotics.
86 96% of 1st cultures positive
98 100% of 1st 2 cultures positive

Blood cultures may be negative if the patient

has already received antibiotics; a few cases
of infective endocarditis are culture-negative
BIAKAN DARAH

lebih dianjurkan sampel darah arteri

saat suhu tubuh meningkat ?
dilakukan paling sedikit 3 kali, jarak 1 jam
tusukan langsung
sampel : 2 tabung (aerob dan anaerob) berisi 50 ml
media + 10 ml darah dibiakkan suhu 37o c selama
5-6 hari
keadaan khusus :
- sepsis antibiotik empiris setelah ambil
sampel
- terapi antibiotik jangka pendek stop 3 hari
- terapi antibiotik jangka panjang stop 6-7
hari

ESC guidelines
DIAGNOSIS
Kriteria mayor
1. Biakan darah positif
a. Mikroorganisme tipikal untuk EI dari 2 biakan
darah terpisah :
- S. viridans, S. bovis, HACEK
- S. aureus atau enterokokus tanpa ditemukan
fokus primer
b. Biakan tetap positif, apabila
- > 2 sampel positif dengan jarak pengambilan
12 jam
atau
- Tiga sampel atau mayoritas dari 4 sampel
atau lebih hasil positif, dengan jarak waktu
pengambilan pertama dan terakhir paling sedikit
1 jam
DIAGNOSIS
2. Bukti keterlibatan endokardium

a. Ekokardiogram positif apabila :

- Massa dalam jantung pada katup atau
struktur yang menunjang katup
atau pada aliran regurgitasi
- Abses atau
- Tonjolan baru dari katup buatan atau
regurgitasi katup yang baru
(perburukan atau perubahan bising yang
sebelumnya tidak ada)

b. Regurgitasi katup yang baru

DIAGNOSIS
Kriteria Minor
a. Adanya faktor predisposisi (kelainan jantung atau
penyalahguna obat)
b. Demam > 38 celcius
c. Fenomena vaskuler : emboli arteri mayor, infark paru
septik, anuerisma mikotik, perdarahan intrakranial, lesi
Jeneway, perdarahan konjungtiva
d. Fenomena imunologi : glomerulonefritis, nodus osler,
bintik roth
e. Bukti mikrobiologi : biakan positif tetapi tidak memenuhi
kriteria mayor atau kelainan serologis sesuai EI.
f. Hasil ekokardiografi yang sesuai dengan endokarditis
infektif tetapi tidak memenuhi kriteria mayor.
GAMBARAN EKOKARDIOGRAFI
ALGORITME PEMERIKSAAN EKOKARDIOGRAFI

KECURIGAAN EI

SEGERA TTE

BILA MELIBATKAN ALAT/ KATUP BUATAN

- +
KUALITAS GAMBAR BAIK
+ -
TTE POSITIF
+ -

DICURIGAI ATAU KECURIGAAN

DIDOKUMENTIR
KOMPLIKASI ATAU
BEDAH SELAMA RENDAH TINGGI TEE
FASE AKTIF EI
- +

ESC guidelines
Principles of Therapy

Bactericidal antibiotics must be used

Prolonged therapy is necessary (weeks)
Treatment is best started after multiple sets of blood
cultures have been taken.
Urgency in the initiation of therapy is required for acute
but not subacute endocarditis.
Synergistic combinations of antibiotics are used when
available.
PENATALAKSANAAN

EVALUASI :
- DEMAM MENETAP
ULANGAN BIAKAN DARAH (8 MGG
SETELAH DARAH I)
- BERHASIL : BIAKAN DARAH NEGATIF
SETELAH 7 HARI PENGOBATAN
- GAGAL : BIAKAN DARAH POSITIF
SETELAH 10 HARI PENGOBATAN
PENATALAKSANAAN

1. Medikamentosa
Terapi endokarditis oleh karena
streptokokus
Penisilin G : 12 20 juta IU/ 24 jam iv, dibagi dalam 4-6 dosis
Ceftriakson : 2 gr i.v dosis tunggal (infuse cepat). Bila
diberikan secara intramuskular, sebaiknya hanya 1 gram dalam
satu lokasi suntikan.
Vankomisin : 30 mg/kg/hari iv dibagi dalam 2 dosis (lama
pemberian tidak kurang dari 45 menit).
Teicoplanin : 10 mg/kg i.v 2 kali sehari dalam 9 dosis pertama,
dilanjutkan dengan 10 mg/kg hari dosis tunggal.
Aminoglikosid : diberikan dalam 2 dosis perhari. Merupakan
terapi kombinasi dengan obat tersebut di atas, selama 2
minggu perawatan pertama.
PENATALAKSANAAN

2. Bedah
INDIKASI :
NVE : - gagal jantung
- demam menetap
- destruksi jaringan sekitar katup
- kuman penyebabnya adalah jamur, Brucella spp,
Coxiella spp
- emboli berulang
- destruksi katup
- komplikasi neurologi
PENATALAKSANAAN

Jamur Candida spp

CNE (Culture Negative Endocarditis )

Terapi empiris terhadap Culture Negative Endocarditis

pada NVE atau PVE

NVE

Vankomisin 15.0 mg/kg iv setiap 12 jam 4-6 minggu

+ gentamicin 1.0 mg/kg i.v setiap 8 jam 2 minggu

PVE

Vankomisin 15.0 mg/kg i.v setiap 12 jam 4-6 minggu

+ Rifampisin 300-450 p.o setiap 8 jam 4-6 minggu
+ Gentamisin 1.0 mg/kg i.v setiap 8 jam 2 minggu
PENATALAKSANAAN
Terapi endokarditis oleh karena kuman jenis lain
Gram negatif
Enterobacteriaceae : beta laktam dosis tinggi +
gentamisin 3 mg/kg hari dalam 2-3 dosis selama
4-6 minggu
Pseudomonas : beta laktam dosis tinggi dengan
antipseudomonas + tobramisin 3 mg/kg/hari
dalam 2-3 dosis selama 6 minggu
HACEK : generasi III cephalosporin, misalnya
ceftriakson 2 gr/hari iv dosis tunggal selama 3-4
minggu pada NVE dan 6 minggu pada PVE. Selain
itu Ampisilin sampai 12 gr/hari dalam 3-4 dosis +
gentamisin (3 mg/kg/hari dalam 2-3 dosis)
Coxiella burnette : Doksisiklin 100 mg iv setiap 12
jam + Rifampin
PENATALAKSANAAN

Terapi endokarditis karena enterokokus dan

streptokokus resistens terhadap penisilin

Penisilin MIC < 8 mg/l dan Penisilin G 16-20 juta IU terbagi 4-6 dosis +
gentamisin MIC < 500 mg/l gentamisin 3 mg/ kg /24jam terbagi 2 dosis
selama 4 mgg

Alergi penisilin dan enterococal yang Vankomisin 30 mg/kg/24 jam iv dosis terbagi 2
suseptibel terhadap penisilin/ + gentamisin seperti di atas selama 6 mgg
Gentamisin

Resisten terhadap penisilin Vankomisin 30 mg/kg/24 jam iv dosis terbagi 2

+ gentamisin seperti di atas selama 6 mgg
PENATALAKSANAAN
Terapi pada NVE dan PVE oleh karena
Streptokokus
Regimen A NVE : suseptibilitas penuh terhadap penisilin (MIC < 0,1 mg/l)
Usia < 65 th,
serum kreatinin normal
Kondisi sama dg di atas
tanpa komplikasi dan
respon terapi cepat
Usia > 65 th dan atau
serum kratinin meningkat
atau alergi penisilin
Alergi penisilin atau
Sepalosprorin
Regimen B :suseptibiliti
Regimen C resisten terhadap penisilin, MIC > 0,5 mg/l
Penisilin G 12-20 juta UI/24 jam iv terbagi 4-6 dosis selama
4 mgg + gentamisin3 mg/ kg 24jam (max 240mg/hr), terbagi
2-3 dosis selama 2 mgg
Penisilin G 12-20 juta UI/24 jam iv terbagi 4-6 dosis selama
2 atau 4 mgg dilanjutkan terapi ambulatoarsetelah 7 hari
perawatan di rumah sakit
Penisilin G sesuai fungsi ginjal selama 4 mgg atau
ceftriaxon 2 g/ 24 jam dosis tunggal selama 4 mgg
Vankomisin 30 mg/kg/24 jam iv dosis terbagi 2 selama 4 mgg
terhadap penisilin (MIC 0,1 mg/l-0,5 mg/l) atau PVE
Penisilin G 12-20 juta UI/24 jam iv terbagi 4-6 dosis atau
Ceftriaxon 2 gr / 24 jam dosis tunggal selama 4 mgg +
gentamisin 3 mg/ kg /24jam terbagi 2-3 dosis selama 2 mgg
Terapi sama dengan enterokokus
PENATALAKSANAAN

Terapi Endokarditis oleh karena

Staphylococcus
Regimen A NVE
Oksasilin 8-12 gr/24 jam iv,terbagi 4 dosis selama
MSSA tidak alergi penisilin
minimal 4 mgg + gentamisin 3 mg/ kg /24jam (max
240mg/hr), terbagi 3 dosis pada 3-5 hari pertama
MSSA alergi penisilin Vankomisin 30 mg/kg/24 jam iv dosis terbagi 2 selama
4-6 mgg + gentamisin 3 mg/ kg /24jam ( maksimal
240mg/hr), terbagi 3 dosis pada 3-5 hari pertama
Vankomisin30 mg/kg/24 jam iv dosis terbagi 2 dosis
MRSA
selama 6 mgg

Regimen B PVE
MSSA Oksasilin 8-12 gr/24 jam iv,terbagi 4 dosis + rifampicin
900 mg/24 jam iv terbagi 3 dosis, selama 6-8 minggu, +
gentamisin 3 mg/ kg /24jam (max 240mg/hr), terbagi 3
dosis selama 2 mgg opertama pengobatan
MRSA, CONS Vankomisin30 mg/kg/24 jam iv dosis terbagi 2 selama
6 minggu, + rifampisin 300 mg/ 24 jam iv terbagi 3
dosis, + gentamisin 3 mg/ kg /24jam ( maksimal 240

mg/hari) terbagi 3 dosis, seluruhnya selama 6-8 mgg

ESC guidelines
 Dura
Bacterial Susceptible/Resistant Regimen Dosage and route tion
Viridan 1218 million U/24 h IV either continuously or in
Streptococci Penicillin susceptible Penicillin G Sodium 4 or 6 equally divided doses 4 wk
Streptococcus Ceftriaxone Sodium* + 2 g/24 h IV/IM in 1 dose + 3 mg/kg per 24 h
bovis Gentamicin IV/IM in 1 dose 2 wk
Vancomycin
hydrochloride 30 mg/kg per 24 h IV in 2 equally divided dose 4 wk
Viridan 24 million U/24 h IV either continuously or in 46
Streptococci Relatively Penicillin Resistant Penicillin G Sodium equally divided doses 4 wk
Streptococcus Ceftriaxone Sodium + 2 g/24 h IV/IM in 1 dose + 3 mg/kg per 24 h
bovis Gentamicin IV/IM in 1 dose 2 wk
Vancomycin
hydrochloride 30 mg/kg per 24 h IV in 2 equally divided dose 4 wk

Staphylococci Oxacillin-susceptible strains Nafcillin or oxacillin 12 g/24 h IV in 46 equally divided doses 6 wk

Optional addition of
gentamicin 3mg/kg/24h IV/IM in 2 or 3 equally divided doses 3-5 d

For penicillin allergic Cefazolin 6 g/24 h IV in 3 equally divided doses 6 wk

Optional addition of 3 mg/kg per 24 h IV/IM in 2 or 3 equally divide
gentamicin doses 3-5 d

Oxacillin-resistant strains Vancomycin 30 mg/kg per 24 h IV in 2 equally divided doses 6 wk

* Ceftriaxone alone could be administrated for 4 weeks instead of Penicillin G Circulation 2005;111;e394-e433
 Durati
Bacterial Susceptible/Resistant Regimen Dosage and route on
Viridan 24 million U/24 h IV either continuously or in 4
Streptococci Penicillin susceptible Penicillin G Sodium or 6 equally divided doses 6 wk
Streptococcus Ceftriaxone Sodium + 2 g/24 h IV/IM in 1 dose + 3 mg/kg per 24 h 6 wk +
bovis Gentamicin IV/IM in 1 dose 2 wk

Vancomycin hydrochloride 30 mg/kg per 24 h IV in 2 equally divided dose 6 wk

Viridan Relatively Penicillin 24 million U/24 h IV either continuously or in
Streptococci Resistant Penicillin G Sodium 46 equally divided doses 6 wk
Streptococcus Ceftriaxone Sodium + 2 g/24 h IV/IM in 1 dose + 3 mg/kg per 24 h
bovis Gentamicin IV/IM in 1 dose 6 wk

Vancomycin hydrochloride 30 mg/kg per 24 h IV in 2 equally divided dose 6 wk

Oxacillin-susceptible Nafcillin or oxacillin + 12 g/24 h IV in 6 equally divided doses+900
Staphylococci strains Rifampin mg per 24 h IV/PO in 3 equally divided doses > 6 wk
3 mg/kg per 24 h IV/IM in 2 or 3 equally divide
Gentamicin doses 2 wk

30 mg/kg per 24 h IV in 2 equally divided

doses+900 mg/24 h IV/PO in 3 equally divided
Oxacillin-resistant strains Vancomycin+Rifampin doses >6 wk
3 mg/kg per 24 h IV/IM in 2 or 3 equally divide
Gentamicin doses 2 wk

Circulation 2005;111;e394-e433
Bacterial Susceptible/Resistant
Penicillin, Genytamycin,
Enterococci Vancomycin Susceptible
Penicillin, Streptomycin,
Vancomycin Susceptible,
Gentamicin Resistant
Vancomycin, aminoglycoside
Susceptible, Penicillin Resistant
Intrinsic Penicillin resistant
Penicillin,
Aminoglycoside,Vancomycin
Resistant E faecium
Penicillin,
Aminoglycoside,Vancomycin
Resistant E faecalis
Regimen Dosage and route Duration
Ampicillin sodium 12 g/24 h IV in 6 equally divided doses 4-6 wk
Penicilin G 1830 million U/24 h IV either continuously or in 6 equally divided
sodium+Gentamicin doses+3 mg/kg per 24 h IV/IM in 3 equally divided doses 4-6 wk
30 mg/kg per 24 h IV in 2 equally divided doses+3 mg/kg per 24 h
Vancomycin+Gentamicin IV/IM in 3 equally divided doses 6 wk
Ampilin sodium 12 g/24 h IV in 6 equally divided doses 4-6 wk
24 million U/24 h IV continuously or in 6 equally in divided
Penicillin G +Streptomycin doses+15 mg/kg per 24 h IV/IM in 2 equally divided 4-6 wk
30 mg/kg per 24 h IV in 2 equally divided doses+15 mg/kg per 24 h
Vancomicin+Streptomycin IV/IM in 2 equally divided doses 6 wk
Ampicillin- 12 g/24 h IV in 4 equally divided doses+3 mg/kg per 24 h IV/IM in
Sulbactam+Gentamicin 3 equally divided doses 6 wk
30 mg/kg per 24 h IV in 2 equally divided doses+3 mg/kg per 24 h
Vancomycin+Gentamicin IV/IM in 3 equally divided doses 6 wk
Linazolid 1200 mg/24 h IV/PO in 2 equally divided doses > 8 wk
Quinupristin-dalfopristin 22.5 mg/kg per 24 h IV in 3 equally divided doses > 8 wk
Imipenem/cilastatin+Ampi 2 g/24 h IV in 4 equally divided doses+12 g/24 h IV in 6 equally
cillin divided doses > 8 wk
Ceftriaxone Sodium +
Ampicillin 2 g/24 h IV/IM in 1 dose+12 g/24 h IV in 6 equally divided doses > 8 wk
Circulation 2005;111;e394-e433
 Regimen Dosage and route Duration

HACEK Ceftriaxone sodium 2 g/24 h IV/IM in 1 dose 4 wk

Ampicillin- sulbactam 12 g/24 h IV in 4 equally divided doses 4 wk

Ciprofloxacin 1000 mg/24 h PO or 800 mg/24 h IV in 2 4 wk

Circulation 2005;111;e394-e433
Bacterial Valves Regimen Dose Duration
12 g/24 h IV in 4 equally divided
doses+3 mg/kg per 24 h IV/IM in
Culture Negative Native Valve Ampicillin-sulbactam+Gentamicin 3 equally divided doses 4-6 wk
30 mg/kg per 24 h IV in 2 equally
divided doses+3 mg/kg per 24 h
Vancomycin+Gentamicin IV/IM in 3 equally divided doses 4-6 wk

1000 mg/24 h PO or 800 mg/24 h IV in

plus ciprofloxasin 2 equally divided doses 4-6 wk

Bacterial Valve Regimen Dosage and route Duration

30 mg/kg per 24 h IV in 2 equally
Prosthetic divided doses+3 mg/kg per 24 h
Culture Negative Valve Vancomycin+Gentamicin IV/IM in 3 equally divided doses 6 +2 wk
6 g/24 h IV in 3 equally divided
doses+900 mg/24 h PO/IV in 3
plus Cefepim+Rifampin equally divided doses 6 wk

Circulation 2005;111;e394-e433
Anti Bacterial Therapy for Culture negative

Bacterial Bartonella Regimen Dosage and route Duration

2 g/24 h IV/IM in 1 dose+3

mg/kg per 24 h IV/IM in 3
Culture Negative Suspected Ceftriaxone+Gentamicin equally divided doses 6 + 2 wk

200 mg/kg per 24 h IV/PO in 2

with/without Doxycycline equally divided doses 6 wk

200 mg/24 h IV or PO in 2
equally divided doses+3
mg/kg per 24 h IV/IM in 3
Documented Doxycycline+Gentamicin equally divided doses 6+2 wk

Circulation 2005;111;e394-e433
TIMING OF SURGERY
TIMING OF SURGERY
 Prosthetic cardiac valves, including
bioprosthetic and homograft valves
Previous bacterial endocarditis
Complex cyanotic congenital heart
disease (eg, single ventricle states,
transposition of the great arteries,
tetralogy of Fallot)
Surgically constructed systemic
pulmonary shunts or conduits
 Most other congenital cardiac
malformations (other than above and
below)
Acquired valvular dysfunction (eg,
rheumatic heart disease)
Hypertrophic cardiomyopathy
Mitral valve prolapse with valvular
regurgitation and/or thickened leaflets
 Isolated secundum atrial septal defect
Surgical repair of atrial septal defect,
ventricular septal defect, or patent
ductus arteriosus
(without residua beyond 6 mo)
Previous coronary artery bypass graft
surgery
Mitral valve prolapse without valvular
regurgitation *
 Physiologic, functional, or innocent heart
murmurs
Previous Kawasaki disease without
valvular dysfunction
Previous rheumatic fever without valvular
dysfunction
Cardiac pacemakers (intravascular and
epicardial) and implanted defibrillators
 Respiratory Tract
ET intubation
Flexible bronchoscopy
PE tubes
GI Tract
TEE
EGD
 GU Tract
Vaginal hysterectomy
Vaginal delivery
C - section
In uninfected tissue:
D and C/Ab
Urethral cath
Sterilization
IUDs
Circumcision
Prophylaxis Recommended
Dental procedures - extractions, cleaning with
bleeding, periodontal procedures
Respiratory tract - tonsillectomy, rigid
bronchoscopy
Gastrointestinal - schlerotherapy, biliary tract
surgery
Genitourinary - C-section, cystoscopy, prostate
surgery
JAMA 277:1794, 1997
Dental, Oral, Oesophageal procedure

Not alergic Penicillin Alergic Penicillin Route Time

2 g Amoxicillin 600 mg Clindamycin Oral/ IV 1/2-1 h before

(Child: 50 mg/kg) (Child: 20 mg/kg)

500mg
Azithromycin/Clarithromycin Oral 1 h before

ESC guideline; European Heart J 2004;00, 1-37

 Prophilaxis Regimen
Genitourinary or Gastrointestinal
Tract. Procedure

Not allergic Penicillin

High risk Route Time Moderate risk Route Time

2g
2 g Amoxicillin+1.5mg/kg I.V. or Amoxicillin/
gentamicin I.M. 1/2-1 h before Ampicillin I.V./p.o. 1/2-1 h before

1g Amoxicillin/Ampicillin p.o. 6 h later

Allergic Penicillin

High risk Route Time Moderate risk Route Time

1g Vancomycin+1.5mg/kg over 1-2 h over 1-2 h
Gentamicin I.V./I.M. before 1g Vancomycin I.V./I.M. before
ESC guideline; European Heart J 2004;00, 1-37
KOMPLIKASI

Emboli
Komplikasi paru
Gagal jantung
Miokarditis,
Acute Renal Failure
Gangguan konduksi
 Congestive Heart Failure:

Greatest impact on prognosis.

Moderate to severe: 20% of case.
Develop acutely from perforation, rupture,
valve obstruction, progressive worsening
of valve dysfunction
2/3may progress to severe CHF within the
first month of therapy

Circulation 2005;111;e394-e433
 Risk of Embolization:

Occurs in 22%- 50% of Cases.

The highest incidence seen in mitral and aortic valve.
Most emboli occur within the first 1-2 week of
therapy.
Increased risk in staphylococcal, streptococci, fungal
cause or increasing vegetation size during therapy

Periannularextension of Infection
Splenic Abscess
Mycotic Aneurysms

Circulation 2005;111;e394-e433
 Myocarditis

Uncommon
(1% at autopsy)
(but 5% of patients in influenza,
polio, Coxsackie virus epidemics)

Slight male predominance

(male : female ratio 6 : 4)

Usually with pericarditis

(hence the term myopericarditis)
Myocarditis is clinically and pathologically defined
as inflammation of the myocardium.

Despite this unambiguous definition, the

classification, diagnosis, and treatment of
myocarditis continue to prompt considerable
debate among clinicians.
*THE POSTVIRAL AUTOIMMUNITY HYPOTHESIS
*ANTIGENIC MIMICRY HYPOTHESIS
*DIRECT VIRAL INJURY HYPOTHESIS
*DIRECT IMMUNE INJURY HYPOTHESIS
 Myocarditis

Requires cardiac biopsy

(generally transvenous right ventricular)
for the diagnosis

Most commonly viral

(Coxsackie B2, B3, B4 and B5 cause
up to 44% of sporadic cases in adults)
 Viral Myocarditis

Commonly in young, healthy individuals

Usually disseminated infection in neonates
(with 50% mortality)
May have 2 phases:
1. early direct viral infection of myocytes
2. later auto-immune attack on myocytes
 Viral Myocarditis

Manifestations

Fever, chest pain, dyspnea,

malaise, myalgias, tachycardia,
pericardial friction rub and
electrocardiographic findings

(May cause sudden death due to arrhythmia)

 Viral Myocarditis: Pathology
Pale mottled flabby dilated heart
multifocal interstitial, usually mononuclear
(primarily lymphocytic) inflammation
associated with myocyte injury and necrosis
(cytoplasmic hypereosinophilia,
loss of cross-striations,
nuclear degeneration and lysis)
 Viral Myocarditis

90% recovery,
10% chronic dilated cardiomyopathy,
death rare (in adults)

Parvovirus B19, hepatitis C virus, adenovirus,

cytomegalovirus, Coxsackie virus or other
enteroviruses in some dilated cardiomyopathy

Steroids and immunosuppressive drugs

dont improve prognosis
 Bacterial Myocarditis

Staphylococcus aureus
(abscesses, part of disseminated infection)

Lyme disease (10%, AV block common)

Rocky Mountain Spotted Fever (50%)

Diphtheria (exotoxin)
 Fungal Myocarditis

1. Candida
- in immunocompromised patients
- causes abscesses or granulomas
- part of disseminated infection

2. Aspergillus
- ditto
 Protozoal Myocarditis

1. Toxoplasmosis
primarily in immunocompromised patients,
with foci of necrosis, chronic inflammation,
intra-myocyte cysts (containing bradyzoites)
and free tachyzoites

2. Trypanosomiasis
Chagas disease, in Latin America (esp. Brazil)
 Definition of Infective Endocarditis

endovascular microbial infection of cardiovascular

structures including endarteritiris of the large
intrathoracic vessels or of intracardiac foreign bodies
facing the blood stream.
ESC Guidelines,2004
(This is not all patients with fever or positive blood culture

Circulation 1997; 95: 1686-1784

 Native Valves-ACC Guidelines:
Detection/characterization of valvular lesions
Detection of vegetations and characterization of
lesions in patients with CHD
Detection of associated abnormalities
Reevaluation studies in complex IE
Evaluation of patients with high suspicion of
culture-negative IE
 Prosthetic Valves-ACC Guidelines:
Detection/characterization of valvular lesions
Detection of associated abnormalities
Reevaluation in complex IE
Evaluation of suspected IE and negative cultures
Evaluation of persistent fever without known
source
 TEE:
Prosthetic valves
Poor visualization on TTE and high suspicion
Detection of associated complications
Preoperative
Reevaluation in complex IE
DIAGNOSIS

DUKES
CRITERIA
PENCEGAHAN

Pemberian obat untuk profilaksis ditujukan

pada pasien-pasien yang mempunyai risiko
tinggi dan sedang
Probabiliti
terjadinya EI tertinggi pada
tindakan terhadap gigi dan mulut

Profilaksis
terhadap kuman enterokokus,
streptokokus bovis dan
enterobacteriaceae
PENDAHULUAN

risiko morbiditi dan mortaliti

diagnosa cepat, terapi efektif serta
penemuan dini terjadi komplikasi
perkembangan risiko, klasifikasi
dan terminologi, kuman penyebab,
kriteria diagnosis, pencegahan, serta
jenis antibiotika
Historical Perspective
.. A concretion larger than a
pigeons egg; contained in the left
auricle. Burns, 1809
Oslers Gulstonian lectures
provided the 1st comprehensive
overview of the disease
Lewis and Grant (1923) were the
first to link a transient bacteremia
with deformed valves as the two
predominant risk factors for
infection
The introduction of penicillin
marked the first successful therapy
for this otherwise lethal infection

Oslers Gulstonian
EPIDEMIOLOGI

- Insidens Endokarditis Infektif 1,7

6,2 kasus dalam 100.000 org /tahun
- Laki-laki : perempuan 1,7:1
- Faktor : jumlah penduduk, infeksi,
protese di bidang jantung dan
pembuluh darah, imunosupresif,
obat-obatan intravena
KESIMPULAN
EI memberi risiko morbiditas dan mortalitas yang
tinggi..
Terminologi EI berdasarkan aktifiti, rekurensi,
anatomi, mikrobiologi.
Faktor risiko penting untuk mencegah terjadinya EI
diantaranya dengan cara memberikan obat
profilaksis sebelum tindakan diagnosis dan terapi.
Gambaran klinis secara umum sama, akibat proses
kardiak dan non kardiak
Diagnosis berdasarkan klinis, pemeriksaan
ekokardiografi terutama TEE, dan biakan darah,
kemudian ditentukan dengan kriteria Duke.
Penatalaksanaan : medikamentosa dan atau bedah
Komplikasi harus diperhatikan selama masa
perawatan
 Immunologic Manifestations of
Infective Endocarditis
Hypergammaglobulinemia; both antigen specific and
polyclonal B cell activation (e.g., rheumatoid factor)
May block IgG opsonic response, accelerate
microvascular damage or stimulate phagocytosis
Vasculitis
Circulating immune complexes
Hypocomplementemia
Clinical syndromes: Lumpy-Bumpy
glomerulonephritis
with deposition of complexes plus complement, Oslers
nodes
PATOGENESIS

Patologi NVE
- Kardiak
- Non kardiak
Endokarditis sisi kanan
Endokarditis sisi kiri

Patologi PVE
PATOGENESIS

TRAUMA MEKANIK, IMUNOLOGIS ENDOKARDIUM

TIDAK INTAK PERLEKATAN MIKROTROMBUS
MIKRORGANISME KE DALAM SIRKULASI
MELEKAT PADA ENDOKARDIUM
BERTAMBAH BANYAK DAN MERANGSANG FORMASI
TROMBUS SELANJUTNYA
VEGETASI

IVDA ?
KLASIFIKASI DAN TERMINOLOGI

Berdasarkan : (a) aktifiti penyakit dan

rekurensi, (b) status diagnosa, (c)
patogenesis, (d) letak anatomi, dan
(e)mikrobiologi
Terminologi baru :
- active mitral valve IE due to Enterococcus faecalis
- healed recurrent PVE due Staphylococcus
epidermidis
- suspected culture negative late mitral valve
endocarditis

ESC guidelines
KLASIFIKASI DAN TERMINOLOGI
Terminologi Endokarditis Infektif
aktifiti rekurens Terminologi
patologi anatomi mikrobiologi
diagnosis

aktif
sembuh

Episode 1a relaps Katup mitral, Mikroorganisme

rekurens Aorta, trikuspid Kultur negatif
dsb Serologis negatif
suspected PCR negatif
definitea Histologis negatif
possible

nativea Early PVE

Late PVE
IVDAb

a bila kolom rekurens, terminologi diagnosis, dan atau patologi tanpa teks, menunjukkan episode pertama
(bukan relaps atau rekurens), definite IE (bukan suspected atau possible) dan keterlibatan katup asli
(native valve)
b intravenous drug abuse

ESC guidelines
PENATALAKSANAAN

PVE : - early PVE

- late PVE
Prevention of Infective Endocarditis
High risk
Prosthetic valve
Complex congenital heart disease
Previous endocarditis
Moderate risk
Acquired valvular dysfunction (e.g. rheumatic valve)
Mitral valve prolapse with regurgitation
Negligible risk
Mitral valve prolapse without regurgitation
Rheumatic fever without valvular dysfunction
AHA Recommendations, JAMA 277:1794, 1997
 Respiratory Tract
Tonsillectomy
Violation of respiratory mucosa.
Rigid bronchoscopy.
Gastrointestinal Tract
Esophageal sclerotherapy or stricture dilation
ERCP
Billiary surgery
Violation of intestinal mucosa
GU Tract
Prostate surgery
Cystoscopy
Urethral dilatation
 Microbiology of Native Valve
Endocarditis in Urban Hospitals
Organisms Percent Cases

Streptococcus spp. 34
Enterococcus spp. 6
Staphylococcus aureus 40
Coagulase-negative staphylococci 5
Gram negative bacilli 6
Fungi 2
Misc. / Polymicrobial 3
Culture negative 4

Karchmer, Scientific American Medicine, 1999

 Risiko tinggi : penyakit jantung bawaan
sianotik, riwayat EI, penyakit katup terutama
regurgitasi aorta dan mitral
Risiko sedang : prolaps katup mitral disertai
regurgitasi atau penebalan katup, stenosis
katup mitral, trikuspid, pulmonal,
kardiomiopati hipertropi
Risiko rendah : defek septum atrium, penyakit
jantung iskemik
Pengguna obat intravena
Pathogenesis:
1. Valvular endothelial injury
2. Platelet + fibrin deposition
3. Microbial seeding
4. Microbial multiplication
Up to 1010 bugs/gm (mature)
GAMBARAN EKOKARDIOGRAFI

Potongan tranesofagus dan transgaster gambaran ventrikel kanan dan kiri,

atrium kanan dan kiri, katup mitral, katup trikuspid, septum interventrikular
dan interatrial, serta aorta.

Eur Heart J 1995

Gross Pathology

+ / - perforation of valve
+ / - adjacent abscess
+ / - fibrotic scarring
+ / - calcification
 Microscopic Pathology

Fibrin, platelets, masses of organisms,

+/- necrosis, +/- neutrophils

Later: +/-lymphocytes, +/- macrophages,

+/- fibroblasts, +/- fibrosis
 Bacterial Factors Involved in the
Pathogenesis of Infective Endocarditis

Serum resistance - i.e. complement

Bacterial adhesins mediate binding to
the nonbacterial thrombus and to
endothelial cells:dextran, fibrinogen-
binding proteins
Invasive potential of bacteria
Ability to elaborate extracellular
proteases
Capacity for metastatic seeding
Stimulation of tissue factor activity