PEMBERIAN ANTIBIOTIK PADA

SEPSIS
Dr. Hadi Sulistyanto, SpPD,
MHKes, Finasim

RS BHAYANGKARA SEMARANG
3 JULI 2013

INFLAMATION AND SEPSIS

Inflammation is a vascular tissue reaction against all
forms of lesion. Basically a process of inflammation is
the body's defenses
SIRS : Systemic Inflamatory Response
Syndrome
SEPSIS : The systemic inflammatory response
to infection.

LESI

INFLAMASI

LOKAL

+ INFEKSI

SEPSIS

SISTEMIK

SIRS

bacterial
viral

Cardiac surgery

sepsis

fungal

Asphyxia/Hypoxia
Systemic
inflammatory
response
Trauma and burns

(SIRS)

parasital

Severe
sepsis or SIRS

shock

others

(Septic shock)
Infective cause

Neonatal lung
affectionS

Others

Noninfective cause

ROLE OF CYTOKINES
IL1,TNF, IL6, IL8, IL-10
netrofil
(Guntur 2000)

ENDOTHEL

INFLAMMATORY TRIAD

Fever
Tachycardia
Flushed skin

GRADASI SEPSIS
SIRS

SEPSIS

SEPSIS BERAT

SEPSIS DENGAN HIPOTENSI

SYOK SEPTIK

DEFINITION
Sepsis is an infection accompanied by
systemic response/inflamtion is marked by
two or more of the following :

Temperature >38C or <36C

Pulse rate >90x/minute

Respiratory rate> 20/minute or PaCO2< 32

mmHg

Leucocyte >12000/mm3, <4000/mm3 or >10% of

immature/band leucocyte

SIRS/SEPSIS : CLINICAL
SYNDROM
COLD

WARM

*Hypothermi : *< 35,6 0C

*Hyperthermi : *38,3 0C

*Tachypneu ( resp > 20 /mnt)

* Tachypneu ( resp > 20 /mnt)

*Tachycardi ( pulse > 100 / mnt)

*Tachycardi ( pulse > 100 / mnt)

*Leukopenia

*Leukocytosis > 12000 / mm3

< 4000 / mm3

*10% > cell imature

*10% > cell imature

Suspected infection (1992)

Suspected infection (1992)

Biomarker dini PCT dan CRP

Biomarker dini PCT dan CRP

(2003)

(2003)

INSIDEN SEPSIS & SEPSIS BERAT

Insiden sepsis USA 400.000 kasus sepsis;

200.000 kasus syok septik; 100.000 kematian

More than 750,000 cases of severe sepsis in US

annually, more than 500 patients die of severe
sepsis daily.

Indonesia data??

Mediator Inflamasi pada Sepsis

MEDIATORS
PRO-

ANTI-

INFLAMMATORY

INFLAMMATORY

Bacterial Endotoxin

Interleukin-10

TNF-

PGE2

Interleukin-1

Protein C

Interleukin-6

Interleukin-6

Interleukin-8

Interleukin-4

Platelet Activating Factor Interleukin-12

(PAF)

Lipoxins

Interferon-Gamma

GM-CSF

Prostaglandins

TGF

COMMON MICROBIAL
ETIOLOGY OF SEPSIS
GRAM

NEGATIVE : 60-70%

GRAM

POSITIVE :

E.coli,

Enterobacteriaceae, Klebsiella sp,

Pseudomonas aeruginosa, Haemophillus influenzae

Streptococcus

pneumoniae, Staphylococcus aureus,

Coagulase Negative Staphylococcus, Group B
Streptococcus

Yeast

: Mucormycosis
Virus : CMV

Andrew d Bradley, Current Diagnostic and Treatment in Infection Disease, 2001

Structureof
ofthe
thecell
cellsurface
surfaceof
ofaagram-negative
gram-negative
Structure
bacterium
bacterium
Porin
Lipoprotein

Receptor protein

LPS

Outer
membrane

Peptidoglycan

Periplasmic
space

Cytoplasmic
membrane

O antigen
Lipid A

Salyers, 1994
Bacterial Pathogenesis a Molecular

CLINICAL CONDITION AND PCT

(NG/ML)

Clinical condition
Health
Local Infection
Systemic Infection
(Sepsis)
Severe Sepsis
Septic Shock
PCT = Pro Calcitonin

PCT (ng/mL)
0.05
0.05
2
10
>>>

PCT AND SEPSIS, SEVERE SEPSIS

& SEPTIC SHOCK

PCT

1000

PENYEBAB DEMAM
1. INFEKSI
2. PENY. KOLLAGEN

8. PENY. ENDOKRIN
9. TRAUMA FISIK

3. PENY. SSP

10. BAHAN-2 KIMIA

4. TUMOR GANAS

11. GGN BALANS CAIRAN

5. PENY. DARAH

12. PSIKOGENIK

6. PENY. KARDIOVASKULER

13. FAKSISI/FALSE

7. PENY. GASTROINTESTINAL

FEVER/DEMAM PALSU
14. FUO (FEVER OF
UNKNOWN ORIGIN)

KAUSA FUO

40% INFEKSI

20% NEOPLASMA

15% PENYAKIT JARINGAN IKAT

SISANYA(25% BERBAGAI SEBAB

5-10% TETAP TIDAK DIKETAHUI

Clinical conditions associated with sepsis

Gastrointestinal
Intravascular
Liver
Central iv line
Gallbladder
Infected prostetic device
Colon
Septic thrombophlebitis
Intraabdominal abscess
Lower respiratory tract
Intestinal obstruction
Community acquired pneumonia
Intraabdominal instrumentation Nosocomial pneumonia
Genitourinary
Empyema
Acute pyelonephritis
Lung abscess
Renal abscess
Cardiovascular
Renal calculi
Acute bacterial endocarditis
Urinary tract obstruction
Myocardial abscess
Prostatic abscess
Central nervous system
Instrumentation
Bacterial meningitis
Pelvic
Brain abscess
Pelvic abscess, peritonitis
Perimeningeal infection
Cuncha B. In : Conn Current Therapy 2003

SYMPTOMS AND SIGNS

Tachycardia

Fever

Tachypnea

Hypotension

Organ dysfunction

MANAGEMENT OF SEPSIS
1. Terapi dasar
2. ANTIBIOTIKA DAN ELIMINASI SUMBER
INFEKSI
3. Resusitasi cairan
4. Nutrisi enteral Imuno nutrisi
5. Terapi suplementatif

1. PENGOBATAN DASAR

Mengatasi penyebab vasodilatasi:

IL-1

(Interneukin-1)
TNF (Tumor Necrosis Factor)
NO (Nitric oxide)
Prostaglandin
Aktivasi

komplemen (C3a, C5a)

ABC (airway, breathing dan circulation):

Oksigen
Koloid

dan kristaloid bergantian

Sodium bikarbonat koreksi asidosis

FACTORS TO BE CONSIDERED FOR

THE CHOICE OF ANTIBIOTICS
Community

versus hospital-acquired
infections/ nosocomial
The anatomical site of the focus of
sepsis
The presence of underlying diseases
Diagnostic or surgical intervention
in the recent past

Samples have to be taken for culture before

the administration of antibiotics
Begin intravenous antibiotics as early
as possible & always within the first
hour

of

recognizing

severe

sepsis

/septic shock
Bactericidal antibiotics should be chosen

ANTIBIOTIC
The probability of effectivenes of antimicrobial
therapy should be at least 90-95 % in severe
infections
Broad-spectrum empirical antimicrobials (3rd
Generation or 4th Generation Cephalosporin)
should be reviewed no later than 48 hours and
stepped down to narrow spectrum agents
promptly when appropriate
The Combination therapy de-escalation
following susceptibilities

Duration of therapy typically limited to 7-10

days: longer if response is slow or there are
undrainable foci of infection or immunologic
deficiencies/HIV
Stop antimicrobial therapy if cause is found
to be non infectious

MAJOR GROUP CEPHALOSPORIN

1st generation

Cefadroxil
Cefazolin
Cephalotin
Cephapirin
Cephalexin/
1
Cephradine/
1
/1 : Oral

2nd

3rd

4th

Generation

Generation

Generation

Cefotetan
Cefoxitin
Cefamandol
e
Cefuroxime
Cefaclor
Cefuroxine
axetil

Cefepime
Ceftriaxon
Ceftazidine Sefpirom
Cefotaxime
Ceftizoxime
Cefoferazone
Cefpodoxine
Ceftinir/1
Ceftibuten/1
Cefixime

COMMON MICROBIAL
ETIOLOGY OF SEPSIS
GRAM

E.coli,

NEGATIVE : 60-70%

Enterobacteriaceae, Klebsiella sp,

Pseudomonas aeruginosa, Haemophillus influenzae

GRAM

POSITIVE :

Streptococcus

pneumoniae, Staphylococcus aureus,

Coagulase Negative Staphylococcus, Group B
Streptococcus

Yeast

:Mucormycosis
Virus : CMV

Andrew d Bradley, Current Diagnostic and Treatment in Infection Disease, 2001

EMPIRIC THERAPIES FOR CLINICAL

PRESENTATIONS
Suspected
Empiric therapy
UNDERLYING
SEPSIS SYNDROME
Sources
Intra-abdominal
sepsis (eg.
perforated
viscus)

Ampicillin OR third generation cephalosporin

and aminoglycoside and metronidazole, OR
ampicillin/ sulbactam OR
ticarcillin/clavulanate OR piperacillin/
tazobactam OR imipenem/MEROPENEM

Fever in
neutropenia
patient

Ceftazidime OR cefepime OR
imipenem/MEROPENEM

Biliary sepsis
(eg,
cholangitis)

Ampicillin and aminoglycoside and

metronidazole, OR piperacillin/tazobactam
OR ticarcillin/clavulanate OR
imipenem/MEROPENEM

Unknown

Andrew DB,

Vancomycin + aminoglycoside + OR
piperacillin/ tazobactam OR
James
MS, CURRENT DTID, 2001
imipenem/MEROPENEM

Perbandingan Dengan Imipenem

Isolat bakteri patogen sejumlah 30.244 dari 9 negara.
Hasil:
Meropenem 4-64 kali lebih aktif dari imipenem thdp
Gram negatif termasuk Pseudomonas aeruginosa, Haemophilus
influenzae, dan Neisseria meningitidis.

Imipenem 4-8 kali lebih aktif dari meropenem terhadap

bakteri Gram positif

Pfaller M.A.;Jones R.N., Diagnostic Microbiology and Infectious Disease, Vol

28 (4), 1997, pp. 157-163(7)

II. RESUSITASI CAIRAN

Perubahan hemodinamika sepsis

Permeabilitas kapiler

Cairan keluar ruang interstital

Cairan intravaskular berkurang

Dilatasi pembuluh darah resistensi

Tekanan darah menurun syok

Restorasi volume intravaskuler

Kristaloid + koloid

KRISTALOID:KOLOID = 4:1 ATAU 3:1;

KECEPATAN TETESAN KOLOID 10-20
ML/KGBB/JAM
MAKSIMAL 1000-1500 ML/24 JAM

TUJUAN RESUSITASI
CAIRAN
- Perbaikan volume darah
- Mengoptimalkan Cardiac Output
- Mengurangi resiko edema paru
- Koreksi acidosis

VASOACTIVE THERAPY

Indikasi vasoaktif
Syok

septik jika mengalami

hipoperfusi jaringan
Tidak

merespon terapi cairan

VASOAKTIF

Dobutamine, -adrenergic agonist

Increasing contractility
Decreasing afterload
Initial dose: 0,5-1 mcg/kg/min/iv continous, then
titrated every few minutes (range 2-20
mcg/kg/min/iv)

 Dopamine
Low

doses: 2-3 mcg/kg/min, stimulation

of dopaminergec & -adrenergic
receptprs:
Glomerular filtration
Heart rate
Contratility Hight doses: > 5 mcg/kg/min,
-adrenergiceffect

Peripheral

vasoconstriction

 Norepinephrine
Vasopressine

(ADH=antidiuretic hormone)

Pheripheral vasoconstriction

VASOPRESSOR AND INOTROPIC

Drug
resceptor
DA
Dobutamin
0
Dopamine
++++
Epinephrin
0
Norepinephrin
0
Contractility
Vasodilatation

Activity to adrenergic
1

++++

++

++++

++

++++

++++

+++

+++

+++

+/++

++/+++
++++
+++
Heart rate

Vasoconstriction

IV. TERAPI SUPLEMENTATIF

Strategi Anti Eksotoksin dan Endotoksin

Monoklonal antibodi

Strategi Anti Mediator

Netralisasi NO

Terapi Herbal??

 Intra

Venus Immuno Globulin (IVIG)

Kortikosteroid

???

Some Immunomodulatory Therapy in Sepsis

Antiendotoxin therapy

Monoclonal or polyconal antibodies

LPS analog, LPS elimination

Specific mediators

anti TNF
TNF receptors
IL-1 RA
Coagulants (AT, activated protein C)
Tissue factor pathway inhibitors
PAF
Arachidonic metabolites
Bradikinin antagonist
Nitric oxide synthase inhibitors

Immunostimulation
Immunoglobulins
G-CSF
IFN
Immunonutrition

Non specific

Corticosteroids
Pentoxifillin
Hemofiltration

Vincent JL, Sun Q, Duboid MJ. Clin Infec Dis 2002;34:1084-93

Supportive Therapy in Sepsis

Oxygenization
Fluid and volume resucitation
Vasopresor and inotropic
Albumine
Blood trasfusion
Nutrition
Blood glucose controlled
Renal dysfuction
Bicarbonate therapy
Corticosteroids
Coagulation disorders
Jindal N, Hollenberg SM, Dellinger RP. Crit Care Clin 2000;16(2):233-49

KESIMPULAN
Sepsis merupakan penyebab utama kematian di
ruangan perawatan, oleh karena itu diperlukan
diagnosis yang lebih dini.
Untuk mencegah terjadinya kematian akibat sepsis
diperlukan penanganan yang adekuat.
Penanganan sepsis diantaranya:
Terapi dasar
Resusitasi cairan
Nutrisi parenteral-imuno nutrisi
Pemberian Antibiotik yang adekuat dalam hal ini
dari golongan MEROPENEM
Pemberian agen vasoaktif