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(1)

ANTIMIKROBA

ANTIMIKROBA

ANTIMIKROBA

ANTIMIKROBA

DAN UJI KEPEKAAN

DAN UJI KEPEKAAN

DAN UJI KEPEKAAN

DAN UJI KEPEKAAN

dr. Evita Mayasari, MKes.

dr. Evita Mayasari, MKes.

Medical Faculty, University of Sumatera Utara

Medical Faculty, University of Sumatera Utara

(2)

OBAT ANTIMIKROBA

OBAT ANTIMIKROBA

OBAT ANTIMIKROBA

OBAT ANTIMIKROBA

Obat

Obat yangyang digunakandigunakan untukuntuk menghambatmenghambat Obat

Obat yang yang digunakandigunakan untukuntuk menghambatmenghambat pertumbuhan

pertumbuhan dandan atauatau membunuhmembunuh bakteribakteri penyebab

penyebab infeksiinfeksi yang yang dapatdapat diberikandiberikan per oral, per oral, parenteral

parenteral atauatau lokallokal sebagaisebagai obatobat luarluar parenteral

parenteral atauatau lokallokal sebagaisebagai obatobat luarluar.. Antibiotika

Antibiotika bahanbahan yang yang dihasilkandihasilkan oleholeh ““biotikbiotik” ” tt kkhl khl k hidhid // ikik ii titi

atau

atau mamakkhlukhluk hiduphidup//mikroorganismemikroorganisme sepertiseperti Bakteri

(3)

ANTIMIKROBA

ANTIMIKROBA

ANTIMIKROBA

ANTIMIKROBA

ANTIBIOTIKA

ANTIBIOTIKA

CHEMOTHERAPEUTIKA

CHEMOTHERAPEUTIKA

ANTI FUNGUS

ANTI FUNGUS

ANTI VIRUS

ANTI VIRUS

ANTI VIRUS

ANTI VIRUS

ANTISEPTIKA ANTISEPTIKA DESINFEKTANSIA DESINFEKTANSIA

(4)

PENEMUAN AWAL ANTIMIKROBA

PENEMUAN AWAL ANTIMIKROBA

PENEMUAN AWAL ANTIMIKROBA

PENEMUAN AWAL ANTIMIKROBA

SALVARSAN :

SALVARSAN : ditemukanditemukan padapada awalawal tahuntahun 1900 1900 oleh

oleh Paul EhrlichPaul Ehrlich untukuntuk pengobatanpengobatan penyakitpenyakit oleh

oleh Paul Ehrlich Paul Ehrlich untukuntuk pengobatanpengobatan penyakitpenyakit Syphilis.(Noble Prize)

Syphilis.(Noble Prize)

PRONTOSIL (Sulfonamide)

PRONTOSIL (Sulfonamide) OlehOleh Gerard Domagk Gerard Domagk 1927

1927 dandan penggunaannyapenggunaannya tahuntahun 1935 (Noble1935 (Noble 1927

1927 dandan penggunaannyapenggunaannya tahuntahun 1935 (Noble 1935 (Noble Prize)

Prize)

SULFADIAZINE 693 = Sulfanilamide

SULFADIAZINE 693 = Sulfanilamide oleholeh British British Team

Team pimpinanpimpinan A J EvansA J Evans tahuntahun 19381938 Team

Team pimpinanpimpinan A.J.EvansA.J.Evans tahuntahun 19381938 PENICILLIN

PENICILLIN oleholeh Alexander FlAlexander Fleemmingmming tahuntahun 1929 1929 dan

dan penggunaannyapenggunaannya tahuntahun 1940 (Noble Prize)1940 (Noble Prize) NYSTATIN

NYSTATIN : : antifungantifungalal pertamapertama dijumpaidijumpai tahuntahun 1949

1949 oleholeh Elisabeth Hazen & BrownElisabeth Hazen & Brown STREPTOMYCIN

STREPTOMYCIN oleholeh Selman Waksman Selman Waksman tahuntahun 1940 (Noble Prize)

(5)

MIKROORGANISME YANG MENGHASILKAN

MIKROORGANISME YANG MENGHASILKAN

AANTI

NTIMIKROBA

MIKROBA

Bakteri

Bakteri

Actinomycetes

Actinomycetes (2100) ((2100) (StreptomycesStreptomyces)) (400) (Genus Bacillus)

(400) (Genus Bacillus)

Fungi (800)

Fungi (800)

(Mold = (Mold = PenicilliumPenicillium & & CephalosporiumCephalosporium))

Algae

Algae

Protozoa

Protozoa

Protozoa

Protozoa

(6)

JENIS DAN CARA KERJA

JENIS DAN CARA KERJA

ANTIMIKROBA

ANTIMIKROBA

Menghambat

Menghambat sintes

sintesis

is

dinding

dinding sel

sel

bakteri

bakteri

Merusak

Merusak permeabilitas

permeabilitas

pp

membran

membran

si

sitoplasma

toplasma

Menghambat

Menghambat sintes

sintesis

is

protein

protein..

Menghambat

Menghambat sintes

sintesis

is

protein

protein..

Menghambat

(7)

PENICICLLIN (Mold =

PENICICLLIN (Mold = PenicilliumPenicillium)) PNC

PNC--G G dandan Penicillin VPenicillin V Methicillin

Methicillin OxacillinOxacillin CloxacillinCloxacillin DicloxacillinDicloxacillin Methicillin

Methicillin, , OxacillinOxacillin, , CloxacillinCloxacillin, , DicloxacillinDicloxacillin Ampicillin

Ampicillin & & AmoxacillinAmoxacillin, , CarbenicillinCarbenicillin, , TicarcillinTicarcillin, , Piperacillin

Piperacillin, , MezlocillinMezlocillin

CEPHALOSPORIN (

CEPHALOSPORIN ( ldld CC h lh l ii ))

CEPHALOSPORIN (

CEPHALOSPORIN (mold = mold = CephalosporiumCephalosporium)) Gen.I

Gen.I : : CefachlorCefachlor, , CephalothinCephalothin, , CephalexinCephalexin Gen.II

Gen.II : : CefuroximCefuroxim, , CefiximeCefixime, , CefoxitinCefoxitin Gen.III :

Gen.III : CefotaximeCefotaxime, , CeftriaxoneCeftriaxone, , CefoperazonCefoperazon Gen.IV

Gen.IV : : CefepimeCefepime, , CefpiromCefpirom

CARBAPENEM

CARBAPENEM :: ImipenemImipenem && MeropenemMeropenem

CARBAPENEM

CARBAPENEM : : ImipenemImipenem & & MeropenemMeropenem

MONOBACTAM

MONOBACTAM : : AztreonamAztreonam GLYCOPEPTIDE

(8)

PENICILLIN GROUP

PENICILLIN GROUP

Penicillins

Penicillins:: penicillin G (penicillin G (PfizerpenPfizerpen; ; BicillinBicillin; ; WycillinWycillin), ), penicillin V (

penicillin V (BetapenBetapen; Pen; Pen--VeeVee K), K), methicillinmethicillin ((StaphcillinStaphcillin), ), ampicillin

ampicillin ((OmnipenOmnipen;; PolycillinPolycillin)) oxacillinoxacillin ((BactocillBactocill )) ampicillin

ampicillin ((OmnipenOmnipen; ; PolycillinPolycillin), ), oxacillinoxacillin ((BactocillBactocill ), ), amoxicillin (

amoxicillin (AmoxilAmoxil; ; BiomoxBiomox; ; PolymoxPolymox), ), ticarcillinticarcillin ((TicarTicar), ), carbenicillin

carbenicillin ((GeocillinGeocillin), ), piperacillinpiperacillin ((PipracilPipracil), ), mezlocillinmezlocillin

((MezlinMezlin), ), bacampicillinbacampicillin ((SpectrobidSpectrobid), ), dicloxacillindicloxacillin ((DynapenDynapen), ),

(( ),), pp (( pp ),), (( yy pp ),),

nafcillin

nafcillin ((NallpenNallpen; ; UnipenUnipen).).

Penicillins

Penicillins plus plus ββ--lactamaselactamase inhibitorsinhibitors or compounds or compounds pre enting antibiotic degradation on the kidne s

pre enting antibiotic degradation on the kidne s:: preventing antibiotic degradation on the kidneys preventing antibiotic degradation on the kidneys: :

amoxicillin +

amoxicillin + clavulanateclavulanate ((AugmentinAugmentin), ), ticarcillin

ticarcillin + + clavulanateclavulanate ((TimentinTimentin), ), i illi

i illi ++ lblb tt ((UU )) ampicillin

ampicillin + + sulbactamsulbactam ((UnasynUnasyn), ), piperacillin

piperacillin + + tazobactamtazobactam ((ZosynZosyn), ), imipenem

(9)
(10)

STRUKTUR DINDING GRAM (+) & GRAM ( STRUKTUR DINDING GRAM (+) & GRAM (--))

(11)

Amphotericin

Amphotericin BB

-- Amphotericin

Amphotericin BB

-- Nystatin

Nystatin

-- Colistin

Colistin

-- Polymixin

Polymixin

Polymixin

Polymixin

Tidak

(12)

::

-- ChloramphenicolChloramphenicol (50S)(50S) -- AminoglycosideAminoglycoside (30S)(30S) -- Erythromycin (50S)Erythromycin (50S)Erythromycin (50S) Erythromycin (50S) -- TetracyclinTetracyclin (30S)TetracyclinTetracyclin (30S)(30S)(30S)

-- LyncomycinLyncomycin (50S)(50S)

Ribosom

Ribosom MamaliaMamalia 80S, 80S, sedangkansedangkan bakteribakteri 70S, 70S, reseptorreseptor d

d bb it 30Sit 30S tt 50S50S pada

pada subunit 30S subunit 30S atauatau 50S.50S. Macrolides

Macrolides : erythromycin, : erythromycin, roxithromycinroxithromycin, , clarithromycinclarithromycin, , azithromycin

azithromycin;; digunakan untuk bakteri Gdigunakan untuk bakteri Gramram (+)(+) ddan an beberapa bakteri G

beberapa bakteri Gramram ((--))..

Lincomycin

Lincomycin dandan ClindamycinClindamycin umumnya digunakan untuk bakteri Gram (+).(+).

(13)

Aminoglycoside

Aminoglycoside : : Streptomycin, Streptomycin, kanamycin

kanamycin, , tobramycintobramycin, and , and amikacinamikacin.. Most of

Most of AminoglycosideAminoglycoside are effective are effective against

against GGramram (+)(+) and and GGramram ((--)) bacteria.bacteria.

A i l id

A i l id bb i id li id l hh Aminoglycoside

Aminoglycoside ::bactericidalbactericidal,, others: others:

bacteriostati bacteriostaticc

(14)

Selective antimicrobial action to a specific

Selective antimicrobial action to a specific

tt k

th 70S ib

f b t i

tt k

th 70S ib

f b t i

attack on the 70S ribosome of bacteria

attack on the 70S ribosome of bacteria

Several medically important antibiotics owe their Several medically important antibiotics owe their yy pp

selective antimicrobial action to a specific attack on the selective antimicrobial action to a specific attack on the

70S ribosome of bacteria

70S ribosome of bacteria, with , with mammalian 80S mammalian 80S

ribosomes

ribosomes left unaffectedleft unaffected

ribosomes

ribosomes left unaffected. left unaffected.

Those that act on the 30S ribosome are: Those that act on the 30S ribosome are:

Amikacin Amikacin Amikacin Amikacin Gentamycin Gentamycin Kanamycin Kanamycin ii Neomycin Neomycin Streptomycin Streptomycin Tobramycin Tobramycinyy

(15)

Antibiotics that act on the 50S

Antibiotics that act on the 50S

i

f h ib

i l d

i

f h ib

i l d

portion of the ribosome include:

portion of the ribosome include:

Chloramphenicol Chloramphenicol Clindamycin Clindamycin Furadantin Furadantin Furadantin Furadantin Fusidic

Fusidic acidacid Lincomycin Lincomycin Nitrofuran Nitrofuran Nitrofuran Nitrofuran Puromycin Puromycin Quinopristin Quinopristin//DalfopristinDalfopristin Spectinomycin Spectinomycin Tetracycline Tetracycline

(16)

Sulfonamide (

Sulfonamide (berkompetisiberkompetisi dengandengan PABA)PABA) Sulfonamide (

Sulfonamide (berkompetisiberkompetisi dengandengan PABA)PABA) Trimethoprim

Trimethoprim ((menghambatmenghambat dihidrofolicdihidrofolic acid acid redu

reducctasetase))

redu

reducctasetase)) Rifampicin

Rifampicin ((StreptomycesStreptomyces,, menghambatmenghambat enz

enziim RNAm RNA polpoliimerasemerase,, mencegahmencegah sintessintesisis enz

enziim RNA m RNA polpoliimerasemerase, , mencegah mencegah sintessintesisis RNA)

RNA)

Pyrimidine

Pyrimidineyy

Quinolone

Quinolone : (: (blokadeblokade DNA DNA gyrasegyrase))

-- NalidixicNalidixic acidacid -- CyprofloxacinCyprofloxacinypyp -- NorfloxacinNorfloxacin -- OfloxacinOfloxacin

(17)

Quinolone

Quinolone

Fluoroquinolones

Fluoroquinolones (synthetic

(synthetic

chemicals) are broad spectrum and

chemicals) are broad spectrum and

chemicals) are broad spectrum and

chemicals) are broad spectrum and

examples include

examples include

norfloxacin,

norfloxacin,

ciprofloxacin enoxacin

ciprofloxacin enoxacin

ciprofloxacin, enoxacin,

ciprofloxacin, enoxacin,

levofloxacin, and trovafloxacin

levofloxacin, and trovafloxacin

.

.

The fluoroquinolones inhibiting one or

The fluoroquinolones inhibiting one or

more of a group of enzymes called

more of a group of enzymes called

g

g

p

p

y

y

topoisomerase, enzymes needed for

topoisomerase, enzymes needed for

bacterial nucleic acid synthesis.

(18)

Inhibisi

Inhibisi Pathway Folic Acid

Pathway Folic Acid oleh

yy

oleh

Sulfonamide

Sulfonamide dan

dan Trimethoprim

Trimethoprim

Sulfona

Sulfonamide mide TrimethoprimTrimethoprim

Pteridine Pteridine HH22

+

+ PurinePurine

P A B A

P A B A FAHFAH22 FAHFAH4 + 4 + CC11 +

+ ((DihydroDihydro ((TetrahydroTetrahydro PyrimidinePyrimidine +

+ ((DihydroDihydro-- ((TetrahydroTetrahydro-- PyrimidinePyrimidine

Glutamic

Glutamic acidacid folic acfolic acidid)) folic acfolic acidid))

Amino acid Amino acid

(19)

Antimicrobial Spectrum

Antimicrobial Spectrum

p

p

BROAD SPECTRUM

BROAD SPECTRUM

: Drugs that are effective

: Drugs that are effective

against a variety of both gram

against a variety of both gram--positive and

positive and

against a variety of both gram

against a variety of both gram--positive and

positive and

gram

gram--negative bacteria

negative bacteria

(e.g., tetracycline, (e.g., tetracycline, streptomycin,

streptomycin, cephalosporinspp yy ,, cephalosporins, pp pp , ampicillin,, ampicillin, pp , ,, sulfonamides).

sulfonamides).

NARROW SPECTRUM

NARROW SPECTRUM

: Those effective

: Those effective

against just

against just G

Gram

ram (+)

(+) bacteria, just

bacteria, just G

Gram

ram ((--))

b

t i

l

f

i

b

t i

l

f

i

bacteria, or only a few species

bacteria, or only a few species

(e.g., penicillin G, (e.g., penicillin G, erythromycin,

(20)

Range of Activity Organisms Affected Example Antibiotics G Narrow Spectrum Gram-positives (Actinomyces, Corynebacteria, Bacillus, Clostridium, Pyogenic cocci,

Macrolides (Erythromycin) Polypeptides (Polymyxin)

Clostridium, Pyogenic cocci,

Spirochetes)

Moderate Spectrum

Gram-positives plus systemic, enteric and

Sulfonamides Aminoglycosides

Moderate Spectrum urinary tract Gram-y

negatives

g y

(Streptomycin, Gentamycin, Tobramycin)

Narrow/Moderate Gram-positives plus Gram- Beta-lactams

Narrow/Moderate Spectrum

Gram positives plus Gram

negatives (Penicillin, Ampicillin, Cephalosporins)

Broad Spectrum

All prokaryotes except

Mycobacteria and Chloramphenicol

Broad Spectrum Mycobacteria and Pseudomonas

p Tetracycline

Isoniazid Ethambutol

Anti-mycobacterial Mycobacteria Isoniazid Ethambutol

(21)

Antibacterial activity (spectrum) of antimicrobial agents.

Aerobic

bacteria Anaerobic bacteria Spectrum Gram Gram Gram Gram

Examples

(+) (-) (+) (-)

Broad + + + + cefoxitin, chloramphenicol, imipenam,

tetracyclines

Intermediate + + + ± carbenicillin, ticarcillin, ceftiofur,

penicillin/clavulanic acid, cephalosporins

+ ± + ± ampicillin, amoxicillin Narrow + aztreonam, polymyxin

+ ± + ± benzyl penicillin Gy p + + aminoglycosides, spectinomycin, sulfonamides, trimethoprim + + enrofloxacinenrofloxacin + + + lincosamides, macrolides,pleuromutilins, vancomycin

(22)

Antimicrobial Effects on Cells

Antimicrobial Effects on Cells

Drugs that actually kill microorganisms are Drugs that actually kill microorganisms are termed

termed

bactericidal

bactericidal

..

Drugs that only inhibit the growth of Drugs that only inhibit the growth of microorganisms are termed

microorganisms are termed gg

bacteriostatic

bacteriostatic

..

The decision to use a bactericidal or The decision to use a bactericidal or bacteriostatic

bacteriostatic drug to treat infectiondrug to treat infection dependsdepends

bacteriostatic

bacteriostatic drug to treat infection drug to treat infection depends depends entirely upon the type of infection.

entirely upon the type of infection.

B

Bactericidactericid agentagents will kill cells that are activelys will kill cells that are actively B

Bactericidactericid agentagents will kill cells that are actively s will kill cells that are actively growing.

growing. BacteriostaticsBacteriostatics, will only inhibit the , will only inhibit the growth of cells; ultimate elimination of the growth of cells; ultimate elimination of the organisms is

organisms is dependent upon host dependent upon host phagocyticphagocytic activity

(23)

Bactericidal

Bactericidal and

and Bacteriostati

Bacteriostaticc

Some antimicrobial agents are

Some antimicrobial agents are cidal

cidal in

in

action: they kill microorganisms (e g

action: they kill microorganisms (e g

action: they kill microorganisms (e.g.,

action: they kill microorganisms (e.g.,

penicillins, cephalosporins,

penicillins, cephalosporins,

streptomycin neomycin

streptomycin neomycin))

streptomycin, neomycin

streptomycin, neomycin).

).

Others are

Others are static

static in action: they inhibit

in action: they inhibit

microbial growth long enough for the

microbial growth long enough for the

body's own defenses to remove the

body's own defenses to remove the

organisms (e.g.,

organisms (e.g., tetracyclines,

tetracyclines,

erythromycin, sulfonamides

(24)

Choice of Antimicrobial

Choice of Antimicrobial

A narrow spectrum is preferable

A narrow spectrum is preferable since it will cause less since it will cause less destruction to the body's normal flora.

destruction to the body's normal flora.

Indiscriminate use of broad spectrum antibiotics can Indiscriminate use of broad spectrum antibiotics can lead to

lead to superinfectionsuperinfection by opportunistic by opportunistic

i i h

i i h

C did

C did

(( t i f tit i f ti ))

microorganisms, such as

microorganisms, such as

Candida

Candida

(yeast infections) (yeast infections) and

and

Clostridium

Clostridium difficile

difficile

(antibiotic(antibiotic--associated associated

ulcerative colitis), when the body's normal flora is ulcerative colitis), when the body's normal flora is ulcerative colitis), when the body s normal flora is ulcerative colitis), when the body s normal flora is destroyed.

destroyed.

Other dangers from indiscriminate use of antimicrobial Other dangers from indiscriminate use of antimicrobial Other dangers from indiscriminate use of antimicrobial Other dangers from indiscriminate use of antimicrobial chemotherapeutic agents include

chemotherapeutic agents include drug toxicity, allergic drug toxicity, allergic reactions to the drug, and selection for resistant

reactions to the drug, and selection for resistant

t i f i i

t i f i i

strains of microorganisms strains of microorganisms. .

(25)

Site of Activity Example Antibiotics

Inhibition of cell wall integrity Lysozyme

Inhibition of cell wall integrity Lysozyme

Inhibition of cell wall synthesis :

1. Biosynthetic enzymes

F f i C l i

1. Biosynthetic enzymes

(cytoplasmic) Fosfomycin, Cycloserine 2. Membrane-bound phospholipid

carrier Bacitracin carrier

3. Polymerization of subunits Beta-lactams

4. Combine with wall substrates Vancomycin

Inhibition of membrane integrity : Surfactants, Polyenes, Polypeptides I hibiti f b Inhibition of membrane synthesis : None

(26)

Inhibition of nucleic acid synthesis : Inhibition of nucleic acid synthesis :

1. Metabolism of DNA 5-Fluorocytosine, Acyclovir, NTP

analogs

2. Replication of DNA Nalidixic acid, Novobiocin,

Nitroimadazoles

3 Synthesis of RNA Rifampin

3. Synthesis of RNA Rifampin

Protein integrity : Phenolics, Heavy metals

Protein synthesis :

1 30S Subunit Streptomycin, Kanamycin, 1. 30S Subunit

Tetracycline

2. 50S Subunit Chloramphenicol, Macrolides

(Clindamycin, Erythromycin)

(27)

Altered Receptors :

1. Beta-lactams Altered Penicillin Binding Proteins

2. Macrolides Methylation of 2 adenine residues in 23S RNA of the 50S subunit

3 Rifampin Single amino acid change in RNA 3. Rifampin

polymerase ß-subunit

4. Sulfonamide/trimethoprim Altered synthetase binds pABA

preferentially/altered reductase for TMP 5. Nalidixic acid Altered gyrase

6. Streptomycin Altered S12 protein in 30S subunit

Decreased Entry : Decreased Entry :

1. Tetracycline Normally biphasic, active transport reduced 2. Fosfomycin (chromosomal) Glucose-6-phosphate transport reduced

Destruction/Inactivation :

(28)

Side effects/Toxic effects Examples

Overgrowth of pathogens Intestinal (C. difficile), Vaginal (Candida)

D i f i t ti l

Depression of intestinal

symbiotes Several

Nephrotoxicity Polypeptides, Aminoglycosides

Nephrotoxicity Polypeptides, Aminoglycosides

Ototoxicity - 8th cranial nerve Aminoglycosides Ophthalmic toxicityp y Ethambutol

Aplastic anemia Chloramphenicol

Hypersensitivity Penicillin

(29)

Cephalosporins

Cephalosporins

1st 1st g

generaenerationtion

2nd 2nd g

generaenerationtion

3rd 3rd g

generaenerationtion

4th 4th g

generaenerationtion

Cefadroxil Cefaclor Cefdinir Cefepime Cefazolin Cefamandole Cefoperaxone Cefpirom

Cefelixin Cefonicid Cefotaxime Cephalothin Ceforanide Ceftazidime

Cephaprin Cefotetan Ceftibuten Cephradine Cefoxitin Ceftizoxime

Cefuroxime Ceftriaxone

(30)

The Future of Chemotherapeutic Agents

The Future of Chemotherapeutic Agents

Many bacterial diseases, previously treatable with

Many bacterial diseases, previously treatable with

antibiotics have become

antibiotics have become

resistant

resistant

to antibiotics

to antibiotics

antibiotics, have become

antibiotics, have become

resistant

resistant

to antibiotics.

to antibiotics.

Chemicals produced by plants and animals are

Chemicals produced by plants and animals are

providing

providing new antimicrobial agents

new antimicrobial agents, including

, including

antimicrobial peptides.

antimicrobial peptides.

New antimicrobials include DNA that is

New antimicrobials include DNA that is

complementary to specific genes in a pathogen;

complementary to specific genes in a pathogen;

complementary to specific genes in a pathogen;

complementary to specific genes in a pathogen;

the DNA will bind to the pathogen's DNA or

the DNA will bind to the pathogen's DNA or

mRNA and inhibit protein synthesis

mRNA and inhibit protein synthesis

mRNA and inhibit protein synthesis.

mRNA and inhibit protein synthesis.

(31)

Message From the Director General

Message From the Director General

WHO (2000)

WHO (2000)

WHO (2000)

WHO (2000)

Drug resistance is the most telling sign that we Drug resistance is the most telling sign that we Drug resistance is the most telling sign that we Drug resistance is the most telling sign that we

have failed to take the treat of infectious diseases have failed to take the treat of infectious diseases serio

seriouusly. It suggests that we have mishandled of sly. It suggests that we have mishandled of disease fighting drugs, by

disease fighting drugs, by misusing, misusing, underusingunderusing and overusing them.

and overusing them.

“A World without Antibiotics”. It could bring back “A World without Antibiotics”. It could bring back to a pre

to a pre--antibiotic age. We are antibiotic age. We are vulnerable without vulnerable without effective medicines.

(32)

Impact of Resistance :

Staph aureus 99% sensitive to penicillin G 1940's

p p

and all other Beta lactam antibiotics.

Staph aureus 75% resistant to penicillin 1970's

Staph aureus 75% resistant to penicillin and ampicillin but still 99% sensitive to flucloxacillin and cephalosporin.

Staph aureus 98% resistant to penicillin and 20% resistant to flucloxacillin and all 1990's Beta lactams.

Vancomycin and Teicoplanin only therapeutic options remaining

therapeutic options remaining.

1995 - Intensive care units - Acinetobacter and Moraxella species resistant to all

1996 Moraxella species resistant to all antibiotics tested.

(33)

MICROBIAL RESISTANCE TO

MICROBIAL RESISTANCE TO

ANTIMICROBIAL CHEMOTHERAPEUTIC

ANTIMICROBIAL CHEMOTHERAPEUTIC

AGENTS

AGENTS

AGENTS

AGENTS

A common problem in antimicrobial

A common problem in antimicrobial

A common problem in antimicrobial

A common problem in antimicrobial

chemotherapy is

chemotherapy is

the development of

the development of

resistant strains of bacteria

resistant strains of bacteria

Most

Most

resistant strains of bacteria

resistant strains of bacteria

. Most

. Most

bacteria become resistant to

bacteria become resistant to

antimicrobial agents by one or more of

antimicrobial agents by one or more of

antimicrobial agents by one or more of

antimicrobial agents by one or more of

the following mechanisms:

(34)

Mekanisme

Mekanisme terjadinya

terjadinya strain

strain resist

resisteen

n

1.

1. Producing enzymes which detoxify or Producing enzymes which detoxify or inactivate the antibiotic

inactivate the antibiotic, e.g.,, e.g., penicillinasepenicillinase

inactivate the antibiotic

inactivate the antibiotic, e.g., , e.g., penicillinasepenicillinase and other beta

and other beta--lactamaseslactamases. . 2.

2. Altering the target site in the bacterium to Altering the target site in the bacterium to d bl k bi di f h ibi i

d bl k bi di f h ibi i reduce or block binding of the antibiotic reduce or block binding of the antibiotic, , e.g., producing a slightly altered ribosomal

e.g., producing a slightly altered ribosomal

subunit that still functions but to which the drug subunit that still functions but to which the drug subunit that still functions but to which the drug subunit that still functions but to which the drug can't bind.

can't bind. 3.

3. Preventing transport of the antimicrobial Preventing transport of the antimicrobial agent into the bacterium

agent into the bacterium, , egeg., producing an ., producing an altered

altered cytoplasmiccytoplasmic membrane or outer membrane or outer membrane

membrane membrane. membrane.

(35)

4.

4. Developing an alternate metabolic Developing an alternate metabolic e e op g a a te atee e op g a a te ate etabo cetabo c pathway to by

pathway to by--pass the metabolic step pass the metabolic step being blocked by the antimicrobial agent being blocked by the antimicrobial agent, , e g overcoming drugs that resemble substrates e g overcoming drugs that resemble substrates e.g., overcoming drugs that resemble substrates e.g., overcoming drugs that resemble substrates and tie

and tie--up bacterial enzymes. up bacterial enzymes. 5.

5. Increasing the production of a certain Increasing the production of a certain bacterial enzyme

bacterial enzyme, e.g., overcoming drugs that , e.g., overcoming drugs that resemble substrates and tie

resemble substrates and tie--up bacterial up bacterial enzymes.

(36)

UJI KEPEKAAN BAKTERI

UJI KEPEKAAN BAKTERI

O

O

TERHADAP ANTIMIKROBA

TERHADAP ANTIMIKROBA

CARA PENGENCERAN

CARA PENGENCERAN

(Dilution

(Dilution

CARA PENGENCERAN

CARA PENGENCERAN

(Dilution

(Dilution

Methods) :

Methods) :

Memakai

Memakai mediamedia caircair Memakai

Memakai media media caircair Memakai

Memakai media media padatpadat

Cara

Cara ini

ini kwantitatip

kwantitatip dan

pp

dan akurat

akurat

CARA DIFUSI

CARA DIFUSI

(Diffusion Methods) :

(Diffusion Methods) :

Memakai

Memakai cakramcakram antimikrobaantimikroba Memakai

Memakai cakramcakram antimikrobaantimikroba Tablet

Tablet antimikrobaantimikroba

Cara

Cara ini

ini kwalitatip

kwalitatip dan

pp

dan rutin

rutin

dilakukan

(37)

CARA PENGENCERAN

CARA PENGENCERAN

CARA PENGENCERAN

CARA PENGENCERAN

KWANTITATIP KWANTITATIP KWANTITATIP KWANTITATIP KHM (Kadar

KHM (Kadar HambatanHambatan Minimal = MIC)Minimal = MIC) KBM (Kadar B

KBM (Kadar Bunuhunuh Minimal = MBC)Minimal = MBC) KBM (Kadar B

KBM (Kadar Bunuhunuh Minimal = MBC)Minimal = MBC) AKURAT

AKURAT

UNTUK PENELITIAN / PERMINTAAN KHUSUS UNTUK PENELITIAN / PERMINTAAN KHUSUS

(38)

CARA PENGENCERAN (lanjutan)

CARA PENGENCERAN (lanjutan)

MEDIA CAIR

MEDIA CAIR

Cara

Cara Makro

Makro

:: seri

seri 12

12 tabung

tabung reaksi

reaksi

Cara

Cara Makro

Makro

:

: seri

seri 12

12 tabung

tabung reaksi

reaksi

Cara

Cara Mikro

Mikro : plat

: plat m

mikrotiter

ikrotiter,

, pipet

pipet mikro

mikro

MEDIA PADAT

MEDIA PADAT

Mueller Hinton Agar

g

AM

AM diencerkan

diencerkan kelipatan

kelipatan dua

dua (1

(1 ug

ug, 0,5

, 0,5 ug

ug,

,

0 25

0 25 ug

ug 0 125

0 125 ug

ug dst

dst))

0.25

0.25 ug

ug. 0.125

. 0.125 ug

ug,

, dst

dst))

Larutan

(39)

CARA DIFUSI

CARA DIFUSI

MEDIA : MEDIA :

Mueller Hinton Agar

Mueller Hinton Agar atau

g

g

atau Sensitest

Sensitest

Agar

Agar

Jika

Jika bakteribakteri fastidifastidiuus : Agars : Agar DarahDarah Jika

Jika bakteribakteri fastidifastidiuus : Agar s : Agar DarahDarah

BAKTERI : BAKTERI :

Bakteri

Bakteri Log phaseLog phase kelarutankelarutan MacFarlandMacFarland 0 50 5 Bakteri

Bakteri Log phase, Log phase, kelarutankelarutan MacFarlandMacFarland 0,50,5 Disemaikan

Disemaikan dengandengan kapaskapas lidilidi sterilsteril 3 streak3 streak

CAKRAM : CAKRAM : CAKRAM : CAKRAM :

Kertas

(40)

MEMBACA DAERAH INHIBISI

MEMBACA DAERAH INHIBISI

Daerah

Daerah inhibisiinhibisi diukurdiukur menggunakan

menggunakan kkalipergggg aliper ((jangkapp ((j gjangkaj g sorong

sorong) ) atauatau penggarispenggaris Lebar

Lebar daerahdaerah inhibisiinhibisi

di ik

di ik dd d fd f disesuaikan

disesuaikan dengandengan daftardaftar dari

dari setiapsetiap AM AM dandan BakteriBakteri yang

yang diujidiuji kepekaannyakepekaannya y g

y g jj pp yy

((setelahsetelah dieramkandieramkan 1818--24 24 jam). jam). Di t k Di t k Dinyatakan Dinyatakan:: Sensiti

Sensitif f ((ssusceptibleusceptible),), Hampir

Hampir resistenpp resisten,,,, Resisten

(41)

ANTIMIKROBA GENUS

Kandungan disk (cakram

AM)

Diameter Zona Hambat (mm) Resisten Intermediat Sensitif Resisten Intermediat Sensitif β-LACTAMS Ampicillin Enterobacteriaceae 10 µg <13 14-16 >17 Staphylococci 10 µg <28 >29 Enterococci 10 µg <16 >17 Carbenicillin Pseudomonas 100 µg <13 14-16 >16 Gram (-) 100 µg <19 20-22 >23

Methicillin Staphylococci 5 µg <9 13-Oct >14

Mezlocillin Pseudomonas 75 µg <15 >16

Other Gram (-) 75 µg <17 18-20 >21

Nafcillin Staphylococci 1 µg <10 12-Nov >13

Oxacillin Staphylococci 1 µg <10 12-Nov >13

Oxacillin Staphylococci

Penicillin Staphylococci 10 units <28 >29

(42)

FAKTOR PENYEBAB RESISTENSI

FAKTOR PENYEBAB RESISTENSI

Faktor

Faktor non

non genetik

genetik ::

AM akan resisten jika bukan pada masa aktif pembelahan bakteri. PadaPada umumnyaumumnya semuasemua AM

AM barubaru bisabisa bekerjabekerja baikbaik padapada masamasa aktiaktiff pembelahan

pembelahan bakteribakteri pembelahan

pembelahan bakteribakteri.. Hilangnya

Hilangnya strukturstruktur target target untukuntuk AM (AM (kehilangankehilangan dinding

dinding selgg sel)),, sehingga)),, sehingga obatgggg obat betalaktambetalaktam jadijadijj resisten

resisten. .

Faktor

Faktor genetik

genetik ::

TerjadiTerjadi perperuubahanbahan genetikgenetik menimbulkan

menimbulkan resistensiresistensi bakteribakteri.. Resistensi kromosomal

R i t i k t k l ( l l i Pl id) Resistensi ekstrakromosomal (melalui Plasmid)

(43)

CARA TERJADINYA RESISTENSI

CARA TERJADINYA RESISTENSI

INTRINSIC

INTRINSIC

::

Hal

Hal iniini biasabiasa untukuntuk semuasemua spespessiesies dimanadimana spespessiesies tertentutertentu tid k

tid k memp n imemp n i t gett get tt e eptoe epto nt knt k ntimik obntimik ob tidak

tidak mempunyaimempunyai target target atauatau reseptorreseptor untukuntuk antimikrobaantimikroba, , atau

atau adaada barrier barrier alamiahalamiah a.la.l.:.: =

= BakteriBakteri anaeroba ea e a ae obanaerob terhadapa ae ob e adapterhadap Aminogle adap Aminoglikogog os dikosidosidaaos daa = Streptococcus

= Streptococcus resistenresisten terhadapterhadap AminoglAminoglikikosidosidaa karenakarena mempunyai

mempunyai //adanyaadanya barierbarier alamiahalamiah.. =

= EnterobacteriaceaeEnterobacteriaceae resistenresisten terhadapterhadap PNCPNC--GG

ACQUIRED

ACQUIRED

: FAKTOR EKSTRA KHROMOSOMAL: FAKTOR EKSTRA KHROMOSOMAL

Modifikasi

Modifikasi genetikgenetik karenakarena mutasimutasi, , tranfertranfer gene gene melaluimelalui

(44)

PLASMID

PLASMID

Plasmid

Plasmid == closed loop of DNAclosed loop of DNA, , elemen elemen genetigenetik yg sangat k yg sangat kecil

kecil ((beratberat kira2 1kira2 1--3% 3% kromosomkromosom bakteribakteri)), , didi luarluar

kkromosomromosom,, membawamembawa gengen resistenresisten terhadapterhadap antimikrobaantimikroba.. kkromosomromosom, , membawamembawa gen gen resistenresisten terhadapterhadap antimikrobaantimikroba.. M

Mampuampu bebereplikasireplikasi didi dalamdalam ssel el bakteribakteri secarasecara autonomautonom Bisa

Bisa berpindahberpindah antarantar spespessiesies (broad host range)(broad host range) Bisa

Bisa berpindahberpindah antarantar spespessiesies (broad host range) (broad host range) Berada

Berada bebasbebas dalamdalam sitoplasmasitoplasma bakteribakteri Salah

Salah satusatu PlasmidPlasmid adalahadalah R FactorR Factor beberapabeberapa R FactorR Factor

Salah

Salah satusatu Plasmid Plasmid adalahadalah R FactorR Factor, , beberapabeberapa R Factor R Factor

membawa

membawa transposontransposon (gen resisten yang bisa berpindah dari satu Plasmid ke Plasmid lainnya atau ke kromosom). Kini dikenal lagi INTEGRON

Contoh

(45)
(46)

CARA PERPINDAHAN GEN

CARA PERPINDAHAN GEN

TRANSDUKSI TRANSDUKSI

Plasmid DNA via

Plasmid DNA via BaBakkterioterioffagagaa ((biasabiasa bakteribakteri GamGam positippositip) ) ditransfer

ditransfer keke populasipopulasi kumankuman lainlain ditransfer

ditransfer keke populasipopulasi kumankuman lain.lain.

TRANSFORMASI

TRANSFORMASI (fragment DNA (fragment DNA bebasbebas dapatdapat melewatimelewati dinding

dinding ssel el dandan kemudiankemudian bersatubersatu dalamdalam genomgenom selsel)).. BiasaBiasa dil k k

dil k k didi l bl b t it i (( kk tiktik)) Pi d hPi d h

dilakukan

dilakukan didi laboratoriumlaboratorium ((rekayasarekayasa genetikgenetik)).. PindahPindah secara

secara spontanspontan

KONYUGASI KONYUGASI

Melalui

Melalui Fertility Factor Fertility Factor makamaka RTF (ResistRTF (Resistaanntt Transfer Transfer Factor)

Factor) pindahpindah daridari satu satu selsel keke selsel lain lain seringsering menyebabkan

menyebabkan multidrugmultidrug resistenresisten.. menyebabkan

menyebabkan multidrug multidrug resistenresisten..

TRANSLOKASI / TRANSPOSISI TRANSLOKASI / TRANSPOSISI

Perpindahan

(47)

CONJUGATIVE TRANSPOSON

CONJUGATIVE TRANSPOSON

Telah

Telah dikenaldikenal type type barubaru elemenelemen conjugative conjugative yaituyaitu Conjugative Conjugative Transposon

Transposon Terdapat

Terdapat didalamdidalam khromosomkhromosom bakteribakteri.. Conjugative

Conjugative TransposonTransposon terintegrasiterintegrasi didalamdidalam Plasmid Plasmid atauatau berada

berada didi dalamdalam khromosomkhromosom bakteribakteri sehinggasehingga lebihgggg lebih susahsusah untukuntuk dideteksi

dideteksi.. Ada

Ada kemungkinankemungkinan bertanggungbertanggung jawabjawab dalamdalam kebanyakankebanyakan transfer Plasmid

transfer Plasmid

Transfer

Transfer terjaditerjadi tidaktidak hanyahanya antarantar species species padapada group group BakteriBakteri Gram(+)

Gram(+) atauatau antarantar group group BakteriBakteri Gram (Gram (--) ) tetapitetapi jugajuga antaraantara Bakteri

Bakteri Gram (+) Gram (+) dandan BakteriBakteri Gram (Gram (--))

Transposons or "jumping genes" are capable of integration into the chromosome of a bacteria or into plasmids. The can be a whole gene or part of a gene.

(48)

INTEGRON

INTEGRON

KINI DIKENAL ELEMENT INTERGRATING

KINI DIKENAL ELEMENT INTERGRATING

BARU = INTEGRON

BARU = INTEGRON

BARU = INTEGRON

BARU = INTEGRON

INTEGRON BERTANGGUNG JAWAB UN

INTEGRON BERTANGGUNG JAWAB UN--TUK

TUK

BERBAGAI PLSMID YANG MEMBA

BERBAGAI PLSMID YANG MEMBA--WA

WA

MULTIPLE DRUG RESISTANCE GENE

MULTIPLE DRUG RESISTANCE GENE

INTEGRON SEPERTI TRANSPOSON

INTEGRON SEPERTI TRANSPOSON

ADALAH SEGMEN DNA LINEAR

ADALAH SEGMEN DNA LINEAR

ADALAH SEGMEN DNA LINEAR.

ADALAH SEGMEN DNA LINEAR.

(49)

RESISTENSI PADA BETALAKTAM :

RESISTENSI PADA BETALAKTAM :

Enz

Enziim m ββ--laktamaselaktamase yang yang dihasilkandihasilkan bakteribakteri membukamembuka ( l )

( l ) ii ii ββ l ktl kt hihi tdktdk ktiktiff B kt iB kt i (cleaves)

(cleaves) cincincincin ββ--laktamlaktam sehinggasehingga tdk tdk aktiaktiff. . BakteriBakteri Gram(

Gram(--) ) menghasilkanmenghasilkan ββ--lalakktamasetamase dalamdalam periplasmaperiplasma sedangkan

sedangkan bakteribakteri Gram(+) Gram(+) : : dalamdalam cairancairan ekstraselulekstraselulaar.r. Tidak

Tidak adanyaadanya PBP (Penicillin Binding Protein) PBP (Penicillin Binding Protein) reseptorreseptor bakteri

bakteri menjadimenjadi resistenresisten. (Alteration of the target of the . (Alteration of the target of the antibiotic)

antibiotic) DalamDalam halhal iniini penambahanpenambahan ββ--laktamaselaktamase antibiotic)

antibiotic) DalamDalam halhal iniini penambahanpenambahan ββ laktamaselaktamase inhibitor

(50)

RESISTENSI PADA

RESISTENSI PADA

BETALAKTAM :

BETALAKTAM :

Betalaktam

Betalaktam tidak

tidak berhasil

berhasil mengaktivasi

mengaktivasi

g

g

autolytic

autolytic enzyme

enzyme ((yang

yang menghancurkan

menghancurkan

peptidogl

peptidoglik

ikan),

an), sehingga

sehingga bakteri

bakteri menjadi

menjadi

toleran

toleran

toleran

toleran..

Resisten

Resisten terhadap

terhadap AM

AM Glycopeptide

Glycopeptide :

: walau

walau

belum

belum jelas

jelas benar

benar tetapi

tetapi 2 gene (

2 gene (vanA

vanA &

&

belum

belum jelas

jelas benar

benar,

, tetapi

tetapi 2 gene (

2 gene (vanA

vanA &

&

vanH

vanH) yang

) yang terlibat

terlibat menye

menye--babkan

babkan dihasilkan

dihasilkan

protein yang

protein yang berbeda

berbeda yang

yang tidak

tidak mengi

mengi--kat

kat

V

i

V

i

Vancomycin

Vancomycin..

(51)

ANTI ENZYME BETALACTAMASE

ANTI ENZYME BETALACTAMASE

Obat

Obat golgol. . betalaktambetalaktam menjadi resisten karena bakteri

menghasilkan enzim betalaktamase yang yang

menghancurkan

menghancurkan cincincincin betabeta laktamlaktam daridari obatobat menghancurkan

menghancurkan cincincincin betabeta--laktamlaktam daridari obatobat.. Enz

Enziim m betalaktamasebetalaktamase tersebuttersebut bisabisa dirusakdirusak dengandengan b hk

b hk l hl h tt tt didi bb hh i ii i menambahkan

menambahkan salahsalah satusatu zatzat didi bawahbawah iniini ::

+

+ Clavulanic

Clavulanic acid (

acid (Augmentin

Augmentin))

+

+ Sulbactam

Sulbactam ((Sulperazon

Sulperazon))

+

+ Tazobactam

Tazobactam

ob c

ob c

((Piperacillin(( pePiperacillin + pe cc + TazobactamTazobactam))ob cob c ))

Penambahan

(52)

MRSA

MRSA,, VISA

VISA,, VRSA

VRSA,, ESBLs

ESBLs

MRSA : Meth

MRSA : Methiicillincillin--rresistantesistant S. S. aaureusureus

MRSA refers to a type of bacteria (

MRSA refers to a type of bacteria (Staphylococcus Staphylococcus

aureus

aureus) that is resistant to many antibiotics. It is a ) that is resistant to many antibiotics. It is a

common cause of hospital

common cause of hospital--acquired infections.pp acquired infections.qq

•• MupirocinMupirocin ointment has also shown promising ointment has also shown promising

results in decreasing nasal carriage. Wide spread use

results in decreasing nasal carriage. Wide spread use gg gg pp

is only indicated in certain settings to avoid

is only indicated in certain settings to avoid mupirocinmupirocin

resistance. resistance.

VISA :

VISA : Vancomycin

Vancomycin Interm

Intermeediate

diate

S.

S. aaureus

ureus

VRSA :

(53)

ESBL = Extended spectrum beta

ESBL = Extended spectrum beta lactamase

pp

lactamase.

.

This term refers to

This term refers to

beta

beta lactamase

lactamase enzymes

enzymes

produced mainly by

produced mainly by

Klebsiella

Klebsiella

and

and

E. coli

E. coli

that

that

encode for resistance to broad

encode for resistance to broad--spectrum

spectrum

β

β--lactam

lactam antibiotics that normally have activity

antibiotics that normally have activity

against Gram

against Gram ((--)) bacilli.

bacilli.

Examples are

Examples are cefotaxime

cefotaxime ceftriaxone

ceftriaxone

Examples are

Examples are cefotaxime

cefotaxime,

, ceftriaxone

ceftriaxone,

,

ceftazidime

ceftazidime,

, aztreonam

aztreonam and

and cefpodoxime

cefpodoxime.

.

These enzymes are

These enzymes are

not active against

not active against

the

the

cephamycins

(54)

AMINOGL

AMINOGLIK

IKOSID

OSIDAA

Ba

Bakkteriterissidalidal, , inainakktitiff pd pH pd pH rendahrendah dandan anaerobanaerob dan

dan MO intraMO intrasselularelular dan

dan MO intraMO intrasselularelular

SSiinergistiknergistik dengandengan grupgrup BetaBeta--lalakktamtam Ampuh

Ampuh untukuntuk bakteribakteri BatangBatang GramGram (( )) Ampuh

Ampuh untukuntuk bakteribakteri BatangBatang Gram Gram ((--)) To

Toksksiikk padapada dosisdosis tinggitinggi Menghambat

Menghambat sintessintesisis proteinprotein dengandengan berberikatanikatan Menghambat

Menghambat sintessintesisis protein protein dengandengan berberikatanikatan pada

pada 30S ribosomal unit 30S ribosomal unit sehinggasehingga tjd tjd

misreading

misreading

mRNA

mRNA mRNA mRNA

Streptomycin,

Streptomycin, KanamycinKanamycin, , GentamycinGentamycin, , Tobramycin

Tobramycin,, AmikacinAmikacin,, NetilmicinNetilmicin Tobramycin

(55)

RESISTENSI PADA AMINOGL

RESISTENSI PADA AMINOGLIK

IKOSID

OSIDAA

RESISTENSI PADA AMINOGL

RESISTENSI PADA AMINOGLIK

IKOSID

OSIDAA

Reseptor

Reseptor subunit 30 S

subunit 30 S hilang

hilang

Reseptor

Reseptor subunit 30 S

subunit 30 S hilang

hilang

Terdapat

Terdapat enz

enziim yang

m yang menghancurkan

menghancurkan

obat

obat ((acethylase

acethylase adenylase

adenylase dan

dan

obat

obat ((acethylase

acethylase,

, adenylase

adenylase dan

dan

fosforilase

fosforilase))

P

bilit

P

bilit

t h d

t h d

b t

b t tt

Permeabilitas

Permeabilitas terhadap

terhadap obat

obat turun

turun,

,

transport

transport obat

obat ke

ke dalam

dalam ssel

el berkurang

berkurang

hi

hi

tid k

tid k

ii Rib

Rib

sehingga

(56)

IMPLIKASI KLINIS RESISTENSI

IMPLIKASI KLINIS RESISTENSI

Timbulnya resistensi bakteri terhadap antimikroba Timbulnya resistensi bakteri terhadap antimikroba bahkan terjadinya multiple drugs resisten

bahkan terjadinya multiple drugs resisten (MDR)(MDR)

bahkan terjadinya multiple drugs resisten

bahkan terjadinya multiple drugs resisten (MDR)(MDR)

bisa mengundang banyak problem berat dalam bisa mengundang banyak problem berat dalam pengobatan penyakit infeksi

pengobatan penyakit infeksi Timbulnya

Timbulnya “Kuman Rumah Sakit”“Kuman Rumah Sakit” yang amat yang amat resisten sebab RS sering menggunakan dosis resisten sebab RS sering menggunakan dosis resisten sebab RS sering menggunakan dosis resisten sebab RS sering menggunakan dosis tinggi dan dalam intensitas tinggi.

tinggi dan dalam intensitas tinggi.

Antibiotik baru perlu riset yg lama (10

Antibiotik baru perlu riset yg lama (10 20 tahun)20 tahun) Antibiotik baru perlu riset yg lama (10

Antibiotik baru perlu riset yg lama (10--20 tahun) 20 tahun) sehingga bisa terjadi

sehingga bisa terjadi tiadanya antibiotikatiadanya antibiotika yang yang bisa digunakan untuk mengobati penyakit infeksi. bisa digunakan untuk mengobati penyakit infeksi. bisa digunakan untuk mengobati penyakit infeksi. bisa digunakan untuk mengobati penyakit infeksi.

(57)

Prevention and control

of antibiotic resistance

of antibiotic resistance

Reduce selective pressures:

1 Use antibiotics for bacterial disease

1. Use antibiotics for bacterial disease

2. Use appropriate dosing and length of time 3. Change medication if ineffective

4 U i t di ti f ifi it

4. Use appropriate medication for a specific site

5. Stop use of antibiotics in the animal husbandry for growth promotion

p

6. Regulate prescribing practices in veterinary medicine

7. Establish antibiotic prescribing practices and distribution especially in countries that allow over the counter

especially in countries that allow over the counter medications without precripton

(58)

Antifungal Drugs

Antifungal Drugs

1. Polyenes, such as nystatin and amphotericin B,

bi

ith l

b

t

l

d

combine with plasma membrane sterols and are

fungicidal.

2. Azoles interfere with sterol synthesis and are used

to treat cutaneous and systemic mycoses

to treat cutaneous and systemic mycoses.

3. Griseofulvin interferes with eukaryotic cell division

and is used primarily to treat skin infections

(59)

Antifungals that bind sterols :

g

Membrane structural differences :

The composition of the fungal plasma membrane differs from the composition of the mammalian plasma

membrane particular in terms of the presence or absence of certain kinds of sterols

of certain kinds of sterols.

There exist antibiotics that, consequently, more effectively recognize fungal plasma membrane than mammalian

recognize fungal plasma membrane than mammalian plasma membrane.

Examples include:

= amphotericin B = nystatin = ketoconazole = miconazole

(60)

Antiviral

Antiviral Drugs

Drugs

g

g

1.

1. AmantadineAmantadine blocks penetration or uncoating of blocks penetration or uncoating of pp gg influenza A virus

influenza A virus..

2

2 Nucleoside and nucleotide analogsNucleoside and nucleotide analogs such assuch as acycloviracyclovir

2.

2. Nucleoside and nucleotide analogsNucleoside and nucleotide analogs such as such as acycloviracyclovir, ,

AZT

AZT, , ddIddI, and , and ddC inhibit DNA or RNA synthesisddC inhibit DNA or RNA synthesis..

3

3 Protease inhibitorsProtease inhibitors such assuch as indinavirindinavir andand saquinavirsaquinavir

3.

3. Protease inhibitorsProtease inhibitors, such as , such as indinavirindinavir and and saquinavirsaquinavir, ,

block

block activity of an HIV enzyme essential for activity of an HIV enzyme essential for assembly of assembly of a new viral coat

a new viral coat..

4.

4. AlphaAlpha--interferonsinterferons inhibit the spread of viruses to new inhibit the spread of viruses to new cells

cells cells. cells.

(61)

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