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Learning objective
- Mahasiswa mampu menjelaskan tanda dan
gejala infeksi
- Mahasiswa mampu menjelaskan pemilihan
antimikroba utk mengatasi penyakit
infeksi

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Pendahuluan
- Tanda dan gejala infeksi :
* Leukositosis (WBC > 10.000/mm3)(N:4.000-10.000)
atau leukopeni ( WBC < 4000/mm3)
* increased production & mobilization of granulocytes
(neutrophils, basophils, and eosinophils), lymphocytes
*Infeksi akutshift to the left (adanya immature
neutrophils )
*Neutropenia : penurunan jumlah neutrofil dlm darah
* demam dgn suhu > 37C (N:36-37C) atau < 36oC

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The explanation :
- WBCs are divided into two groups: granulocytes &
agranulocytes
- Polymorphonuclear (PMN) granulocytes are made up of
neutrophils, basophils, and eosinophils.
- Neutrophils In response to infection leave the
bloodstream and enter the tissue to interact with and
phagocytize offending pathogens.
-Neutrophil :

* Mature neutrophils segmen


* Immature neutrophils bands.
- an acute infection immature neutrophils ( bands )

increased rate and the percentage of bands (usually 5%)


can increase in relationship to mature cells shift to the
left
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Demam, menggigil,hipotermi
Extreme fatigue yg bisa berlangsung > 23 bln
Weight loss berkelanjutan
Nyeri dan sakit seluruh tbh
*Nyeri dan inflamasi : bengkak, eritema, kesakitan, purulent
drainage
Symptoms referable to an organ system :

* Febrile patient with complaints of flank pain and dysuria


pyelonephritis ok E.coli
* Febrile individual with cough and sputum production
pulmonary infection
Catatan :
leukositosis stres, inflamasi ( mis.RA,keganasan),
respon dr obat (mis. korticosteroid)

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- Leukocytosis normal host defense to infection and is an
important adjunct to antimicrobial therapy.
- Neutropenia cancer chemotherapy neutrophil
counts < 500 cells/mm3 high risk for bacterial or fungal
infections
- Lymphocytes (T cell ( immunity) & B cell ( humoral ) the

immune system lymphocytosis acute viral


infections
- ESR) / LED &CRP concentration endocarditis,

osteomyelitis, intraabdominal infections

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Identification Of The Pathogen
- the human body contains microorganisms that colonize
body systems normal flora
* organisms occur naturally in the tissues of the host and
provide some benefits (defense by occupying space,
competing for essential nutrients, stimulating cross-
protective antibodies suppressing the growth of
pathogenic bacteria and fungi )
- Organisms that comprise the normal florapathogenic
when host defenses become impaired or translocated to
other body sites during trauma

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FLORAL NORMAL TUBUH

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Identifikasi kuman itu flora normal or patogen
- Staphylococcus epidermidis (ditemukan di darah pasien
RS )
* normal skin flora & colonizes intravenous catheters.

-kondisi pasien (signs and symptoms, laboratory data )


-kemungkinan m.o penyebab infeksi

If removal of the catheter can eliminate the organism from


the bloodstream

unnecessary application of antimicrobials

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Pewarnaan kuman ( gram staining )
- Menggunakan pewarna crystal violet+ iodium kompleks
crystal violetiodine + alkohol + safranin

-Bakteri gram (+) : warna ungu


-Bakter gram (-) : warna merah
Blood cultures
- the most definitive method available for the diagnosis and
eventual treatment of infection
- A clinical specimen inoculated in a variety of artificial media
bakteri (+) identifikasi

true pathogen, contaminant, normal flora

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GRAM STAIN

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Kuantitatif
MIC ( minimal Inhibitory concentrations )
- the lowest antimicrobial concentration that prevents visible growth of
an organism after approximately 24 hours of incubation in a specified
growth medium.
- in-vitro antibacterial activity
- It is determined through the macrotube dilution method
- It uses liquid growth medium (broth), doubling serial dilutions of
antimicrobials in test tubes, and a standard inoculum of bacteria (
105 CFU/ mL).
- The tubes (up to 10 mL) were incubated at approximately 35C for18
to 24 hours and then examined for visible bacterial growth

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Kualitatif
- It uses selected antibiotic-impregnated disks are placed on
an agar plate previously streaked with a standard suspen-
sion of bacteria (12 108 CFU/mL)
The drug contained in the disk diffuses in a concentration
gradient out into the agar.
- The plate is incubated (18 to 24 hours at 35C)visual

bacterial growth occurs only in areas in which the drug


concentrations are below those required for growth
inhibition.
- The diameters of the zones of inhibition are measured and

are compared with standard zone size ranges determine


susceptibility (S), intermediate susceptibility (I), or
resistance (R)
-

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PENGUKURAN
DIAMETER HAMBAT AB

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Pemilihan AB
Empiris antibiogram RS setempat,patients history,

physical examination,gram stains, performed tests on


specimens from the infected site
- Culture and sensitivity
Host factor :

* alergi obat : alergi AB cephalosporin, cross sensitivity dll


* usia : > 65 thn penurunan fgs nephron penurunaan
fgs renal
* kehamilan : risiko drug teratogenicity, perubahan
farmakokinetik obat penicillins, cephalosporins, and
aminoglycosides
are cleared from the peripheral circulation more rapidly

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* genetic or metabolic abnormalities
- Patients with G6P4 dehydrogenase + sulfonamides,
nitrofurantoin, nalidixic acid, antimalarials, dapsone, and
perhaps, chloramphenicol hemolysis
* Renal and hepatic function
- penyesuaian dosis
- site of infection
- concomitant drug therapy
* INH + phenytoin metab phenytoin dihambat INH
toksisitas fenitoin

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Underlying disease states
Patients with immunosuppressive diseases (malignancy,

HIV-AIDS dll ) highly predisposed to infections


Concomitant Disease States

Trauma, burns, iatrogenic wounds induced in surgery

predisposing to infection (disruption of the hosts inte-


gumentary barriers )
Drug factors

* PK & PD considerations
# concentration-dependent bactericidal effects : aminogly-
coside, fluoroquinolone
- maximize peak:MIC ratio
# time-dependent bactericidal effects : lactam AB (ce-
phalosporin, carbapenem )
- (T > MIC) duration that drug concentrations >the MIC
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Tissue Penetration
* Kadar obat yg rendah pada cairan bilier utk terapi
kolesistitis dan kolangitis dan sedikitnya obat yg rute
eliminasi primer di bilier sbg btk aktif
* Abses
# Penetrasi ke jaringan sulit krn dipengaruhi o/ acid
pH,WBC products,various enzymes can inactivate even
high concentrations of certain drugs

*CNS antimicrobial penetration is relatively well defined


- cth.AB utk penyakit meningitis bakterial

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Drug Toxicity
- Antibiotics associated with CNS toxicities (not dose-

adjusted for renal function


* Penicillins, cephalosporins, quinolones, and imipenem.
- Hematologic toxicities ( prolonged use)
* chloramphenicol bone marrow suppression
* trimethoprim megaloblastic anemia
* aminoglycoside nephrotoxicity,ototoxicity

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MONITOR
Efektivitas terapi
1.Kondisi klinis
tampilan fisik pasien, daerah sekitar infeksi lokal
( inflamasi, sekresi pus atau sekret),nyeri berkurang,
SOB berkirang,batuk or produksi sputum berkurang,
nafsu makan meningkat )
tanda vital suhu, nadi, TD sistemik ( infeksi disertai
syok),kesadaran (infeksi disertai penurunan kesadaran)
2.Data laboratoris
- hasil lab :kdr leukosit dlm drh,leukosuria (ISK),LED
(infeksi kronik TBC), CRP ( TBC, pneumonia)
- gambar radiologis membaik

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Efek samping obat
- Gangguan fgs ginjal:
acute kidney injury : aminoglikosida
Acute interstitial nephritis : kotrimoksazol, ciprofloksasin
- Monitor kadar kreatinin
- Gangguan fgs liver
hepatitis : kloksasillin, amoksiklav, ceftriaxone
- monitor kdr SGPT, SGOT, bilirubin total
- Skin rash, urtikuria : gol penisillin, ciprofloxacine, kotri-

moksazple
- Steven Johnson syndrome : kotrimoksazol, ciprofloxa-

cine
- Bone marrow supression : chloramphenicol

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Lampiran
Klasifikasi organisma infeksius

Rods (bacilli)
Clostridia (Clostridium perfringens, Clostridium tetani, Clostridium difficile)
Propionibacterium acnes
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Golongan
KlasifikasiAntibiotika
Antibiotika

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Folate
Inhibitors

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