Invasi mikroorganisme ke jaringan tubuh

I
n
f Ganggu
e Kolonisasi –
fungsi
normal
tumbuh –
k Menempel
kembang
biak
inang

s inang

i Organisme

2
 Patient
Farmakologist Host Defence

Drug Micro-organism

Microbiologist
 Microbiology Outcome
 Mechanism of action Concentration  Clinical efficacy
 Antibacterial spectrum at infection site  Bacterial eradication
 Antimicrobial Mapping
 Compliance with
Drug Pathogen MIC dosing regimen
 Tolerability
PK PD  Rate of resolution
 Absorption  Prevention of
 Time vs.
 Distribution resistance
concentration
 Metabolism
dependent killing
 Excretion
 Bactericidal vs.
 Optimal dosing
bacteriostatic activity
regimen
 Tissue penetration
 Persistence of antibacterial
(Scaglione, 2002) effect
Empirical therapy

Definite therapy

Prophylaxis

Pre-emptive
 Patient

Microbiological specimen

Empirical antimicrobial therapy

Microbiological result

Definite antimicrobial therapy

 Strategy for
Patient

Outpatient Hospitalized

Stable condition Severe/ high risk

Escalation De-escalation

Antibiotic selection based on

susceptibility and resistance pattern,
immunity status, comorbidity,
organ dysfunction

Antibiotic monotherapy or combination

Pohan HT, 2005
 Microbiological culture results

Colonization Pathogen MDR

Sensitive Resistant

No Treat

Antibiotics Optimized
Treat with Combination PK/PD
Recommended
Antibiotics
YUMC
The Rational Use of Antibiotics
 There is no evidence that antibiotics will prevent
secondary bacterial infection in patients with viral
infection
 Terapi Antibiotik
untuk Infeksi
yang Tidak
Responsif
terhadap Terapi

Terapi untuk
Demam yang
Kurangnya
Penyebabnya
Informasi
Tidak Diketahui
Mengenai Bakteri
(Fever of
Unknown Origin)
Penggunaan
Berlebihan
Antibiotika

Penggunaan
Antibiotik tanpa Dosis yang Tidak
Memperhatikan Tepat
Terapi Definitif

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RESUME GOLONGAN ANTIBIOTIK
TEMPAT INHIBISI GOLONGAN ANTIBIOTIK
Sensitif penisilinase
Penisilin alami (narrow spectrum) Penisilin G, Penisilin V
Aminopenisilin (broad spectrum) Ampisilin, Amoksisilin
Resisten penisilinase (spektrum sangat sempit)
Penisilin
Nafsilin, Oksasilin, Dikloxaksilin
Antipseudomonal (spektrum tambahan)
Karboksi penisilin Tikarsilin, Karbenisilin
Ureido penisilin Piperasilin, Azlosilin, Mezlosilin
Cefazolin, Cefadroxil, Cefadrine
Generasi 1
Cefalexine, Cefapirin, Cefalotin
Cefuroxime, Cefoxitin, Cefotetan
Generasi 2 Cefamandole, Cefonicid, Cefaclor
Beta Laktam
Cefprozil, Cefmetazole, Cefotiam
Sintesa Dinding Sel
Sefalosporin Cefoperazone, Cefdinir,
Cefditoren, Ceftriaxone,
Generasi 3 Ceftrioxime, Ceftributen,
Ceftazidine, Cefotaxime,
Cefixime
Generasi 4 Cefepime, Cefpirome
Generasi 5 Ceftaroline
Karbapenem Meropenem, Ertapenem, Doripenem, Imipenem + Silastatine
Monobaktam Aztreonam
Beta laktamase
Sulbaktam, Tazobaktam, Asam klavulanat
inhibitor
Glikopeptida Vankomisin, Basitrasin, Polimiksin B, Teikoplanin
Non betalaktam
Lainnya Fosfomisin
Aminoglikosida Gentamisin, Amikasin, Neomisin, Tobramisin, Streptomisin
30S
Tetrasiklin Doksisiklin, Tetrasiklin, Tigesilin, Minosilin
Oksazolidonon Linezolid
Protein sintesis Streptogramins Quinupristin / Dalfopristin
50S Kloramfenikol
Makrolida Eritromisin, Azitromisin, Klarithromisin
Lincosamid Klindamisin, Linkomisin
Ciprofloxasin, Sparfloksasin, Nofloksasin, Moxifloksasin,
Florokuinolon
DNA topoisomerase Levofloxasin Gemifloksasin, Ofloksasin, Enofloksasin
Kuinolon Asam Nalidixic
Sulfonamida Sulfamethoxazole, Ag Sulfadiazine, Sulfasalazine, Sulfisoxazole
Sintesa Asam Folat
Inhibitor DFHR Trimetropin, Pirimethamine
DNA (merusak) Metronidazole
mRNA sintetik Rifampin
 IV fluids: Bowel:
incompatible Other drug or food
drug mixtures modifies absorbtion

Kidney: Drug interaction Plasma:

Effect on passive Competitition for
reabsorbtion & protein binding sites
active secretion

Liver: Receptor sites:

Induction of liver enzymes - Drugs may compete
modified excretion at binding site
 Site Antimicrobial Interacting drug/effects

IV fluids Many
Tetracyclines  Absorbtion by food
GI tract Quinolones  Absorbtion reduced by iron

Chloramphenicol Warfarin (antiocoagulant), Sulpho-

Protein binding Co-trimoxazole ureas effects 

Oral contraceptive, warfarin, antidiabetics,

Liver enzyme cyclosporin, etc, metabolism 
Rifampicin , i.e.,  effect
induction

Loop diuretics (frusemide) 

Kidney Aminoglycosides ototoxicity
Diagnosis Klinis
 ‘Ketajaman’ klinis, berdasar

 Terapi Empiris
Diagnosis Laboratorium
 Interpretasi yang tepat
 Bakteri yang tumbuh pada kultur belum
tentu bakteri yang pathogen
 Cara pengambilan spesimen
 Apakah kontaminan atau kolonisasi ?
 Hasil sensitivitas antibiotik merupakan kunci
penting
21
Mouth Skin/Soft Tissue Bone and Joint
Peptococcus S. aureus S. aureus
Peptostreptococcus S. pyogenes S. epidermidis
Actinomyces S. epidermidis Streptococci
Pasteurella N. gonorrhoeae
Gram-negative rods

Abdomen Urinary Tract Upper Respiratory

E. coli, Proteus E. coli, Proteus S. pneumoniae
Klebsiella Klebsiella H. influenzae
Enterococcus Enterococcus M. catarrhalis
Bacteroides sp. Staph saprophyticus S. pyogenes

Lower Respiratory Lower Respiratory Meningitis

Community Hospital S. pneumoniae
S. pneumoniae K. pneumoniae N. meningitidis
H. influenzae P. aeruginosa H. influenza
K. pneumoniae Enterobacter sp. Group B Strep
Legionella pneumophila Serratia sp. E. coli
Mycoplasma, Chlamydia S. aureus Listeria
1. Immunocompetence
2. Immunodeficiency / immunocompromised :
Imunocompromise Primer
• ANA +
• Anti ds DNA+
• Hyper gamma globulinemia
• Hyper Eosinophilia
• Complement Deficiency, etc
Immunocompromised Secunder :
• Neutropenia
• Indwelling medical devices
• Hospitalized patients, esp. ICU patients
• Neoplasm
• Corticosteroid/Cytotoxic agent
• Burn
• Diabetes
• Trauma
• Drugs user, Alcoholic
• Elderly, neonatal, pregnancy and
purpureum
• Dialysis, implants/ prostheses
 absorpsi
 ekskresi
 Level di jaringan
 peak levels, AUC, Time above MIC
Concentration Cmax:MIC Time dependent
T>MIC (CEF)
Concentration dependent
AUC:MIC Cmax>MIC (AM)
AUC>MIC (FQ)

MIC
T>MIC
PAE
0
Time (hours)

MIC = minimum inhibitory concentration; AUC = area under the curve; T = time;
PAE = post antibiotic effect
 Type of bactericidal Important
Dosage optimization
profile parameter

Dose-dependent Cmax / MIC

Aminoglycosides, Single daily dose
quinolones
Prolonged PAE

Time-dependent Multiple DD or
T > MIC No PAE
Penicillin, cephalosporins continuous infusion

Cumulative-dose
dependent AUC / MIC Total dose and
Clarithromycin, Prolonged PAE duration
clindamycin

PAE: Post-Antibiotic Activity

 “serious = parenteral”
 Tidak adanya antibiotik oral yang broad spectrum
dengan bioavailabilitas yang jelas

 Lebih tinggi dan persisten konsentrasinya dalam

serum dan jaringan
 untuk infeksi tertentu efikasinya sebaik parenteral
Keuntungan Terapi Antibiotik Oral
 Routine early review

 change route
 change dose
 change spectrum of antibacterial activity
 stopping antibiotic
 Avoid antibiotic homogeneity
 Promote appropriate use of multiple drug class
 Apply formulary control and restrict of specific agent
or drug class that resistant
 Consider antibiotic cycling, rotation or mixed use
of antibiotic classes
 Develop and promote antibiotic guidelines and
protocol based on local data
1. Unknown focus of infection
2. Increase antimicrobial potency
3. Febrile Neutropenia

Chambers HF. Antimicrobial agents. 2001

 Antibiotics during pregnancy and lactation period
Post
Embryioni Embryo Peripartal
Agent Lactatio Possible foetal impairment
c nic period***
n
period* period**

Penicillin + + + + None known

Cephalos + + + + None known
porins
Aminogly - - - - Inner ear damage
cosides
Erythrom (+) + + + None known, don’t use erythromycin estolate
ycin
Clincamy (+) (+) (+) (+) None known, pseudomembranous enterocolitis im mother
cin
Tetracycli - - - - Disturbance of bone and tooth growth
nes
Chloram - - - - Gray syndrome, myelosuppression
phenicol
Co- - - - - Teratogenic in animal experiments, kernicterus
trimoxaz
ole
- Contraindicated or + safe for use (+) only if clearly A to be prescribed
not recommended when indicated indicated only in exceptional cases

* Embryonic period (1st to 12th wk. of pregnancy) ** Postembryonic period (13th to 39th wk. of pregnancy)

*** Peripartal period (40th wk. of pregnancy till delivery )

 Antibiotics during pregnancy and lactation
period
Post
Embryionic Peripartal
Agent Embryonic Lactation Possible foetal impairment
period * period ***
period **
Fusicid Acid (+) + + + None known
Rifampicin - - - - Coagulation disorder, liver
damage in mother and fetus
Vancomycin (+) (+) (+) (+) None known
Quinolones - - - - Disturbance of chodral growth
Nitrofurantoin - (+) (+) + Teratogenic in animal
experiments
Metronidazole - A A A Teratogenic in animal
experiments
Amphotericin B - A(+) A(+) + Abortion and foetal retardation
reported

- Contraindicated or (+) only if clearly + safe for use A to be prescribed

not recommended indicated when indicated only in exceptional cases

* Embryonic period (1st to 12th wk. of pregnancy)

** Postembryonic period (13th to 39th wk. of pregnancy)
*** Peripartal period (40th wk. of pregnancy till delivery )
 Types of antibiotic usage: empirical, definite,
prophylaxis, pre-emptive

 Rational antibiotic therapy: rapid, appropriate,

cost effective

 The implementation of antibiotic policy to promote:

• rational use of antibiotics,

• cost-effective therapy,

• prevent collateral damage

THANK YOU

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