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
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
ANTIMIKROBA
ANTIMIKROBA
ANTIMIKROBA
ANTIMIKROBA
ANTIBIOTIKA
ANTIBIOTIKA
CHEMOTHERAPEUTIKA
CHEMOTHERAPEUTIKA
ANTI FUNGUS
ANTI FUNGUS
ANTI VIRUS
ANTI VIRUS
ANTI VIRUS
ANTI VIRUS
ANTISEPTIKA ANTISEPTIKA DESINFEKTANSIA DESINFEKTANSIAPENEMUAN 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)
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
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
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
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
STRUKTUR DINDING GRAM (+) & GRAM ( STRUKTUR DINDING GRAM (+) & GRAM (--))
Amphotericin
Amphotericin BB
-- Amphotericin
Amphotericin BB
-- Nystatin
Nystatin
-- Colistin
Colistin
-- Polymixin
Polymixin
Polymixin
Polymixin
Tidak
::
-- 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 (+).(+).
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
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
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
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
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.
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
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,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
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
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
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
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) andand
Clostridium
Clostridium difficile
difficile
(antibiotic(antibiotic--associated associatedulcerative 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. .
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
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)
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 :
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
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
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.
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.
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.
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:
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.
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.
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
CARA PENGENCERAN
CARA PENGENCERAN
CARA PENGENCERAN
CARA PENGENCERAN
KWANTITATIP KWANTITATIP KWANTITATIP KWANTITATIP KHM (KadarKHM (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
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
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
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
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
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 menimbulkanmenimbulkan resistensiresistensi bakteribakteri.. Resistensi kromosomal
R i t i k t k l ( l l i Pl id) Resistensi ekstrakromosomal (melalui Plasmid)
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 KHROMOSOMALModifikasi
Modifikasi genetikgenetik karenakarena mutasimutasi, , tranfertranfer gene gene melaluimelalui
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
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
CONJUGATIVE TRANSPOSON
CONJUGATIVE TRANSPOSON
TelahTelah 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.
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.
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
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..
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
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 :
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
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
mRNAmRNA mRNA mRNA
Streptomycin,
Streptomycin, KanamycinKanamycin, , GentamycinGentamycin, , Tobramycin
Tobramycin,, AmikacinAmikacin,, NetilmicinNetilmicin Tobramycin
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
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.
Prevention and control
of antibiotic resistance
of antibiotic resistance
Reduce selective pressures:
1 Use antibiotics for bacterial disease1. 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
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
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
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.