Antimikroba PDF

ANTIMIKROBA
-Dian Natasya-
Referensi
• Tortora GJ, Funke BR, Case CL. 2001. Microbiology an

Introduction, 7th edition. Benjamin Cummings, San Francisco,
CA 94111, USA
• Lüllmann, 2000, Color Atlas of Pharmacology, Thieme, New
York
• Bauman BR, Machunis-Masuoka E, Tizard I, 2007,
Microbiology with Disease by Taxonomy, 2nd edition,
Pearson Benjamin Cumming, San Francisco, USA
• Todar K, 2009, Antimicrobial Agents in the Treatment of
Infectious Disease, Available from:
http://www.textbookofbacteriology.net/antimicrobial
Sejarah dan Definisi
 Paul Erlich (1854-1915)

• Chemotherapy: penggunaan bahan kimia yang secara
selektif membunuh patogen, tanpa efek/ dengan efek yang
ringan terhadap pasien
 1928: Alexander Fleming
• The growth of Staphylococcus aureus was inhibited in the
area surrounding the colony of a mold that have
contaminated a Petri plate  Penicillium notatum
• Antibiotik: bahan yg dihasilkan oleh mahluk hidup
yg dapat membunuh/menghambat pertumbuhan
mikroorganisme lain.
 Antibiotics ~ antibacterial
Mikroorganisme penghasil antimikroba
Bacillus subtilis Bacitracin

B. polymyxa Polymyxin
Streptomyces venezuelae Chloramphenicol
S. aureofaciens Chlortetracycline & tetracycline
S.nodosus Amphotericin B
S.erythraeus Erythromycin
S.fradiae Neomycin
S.griseus Streptomycin
Micromonospora purpurea Gentamycin
Cephalosporium spp. Cephalotin
Penicillium griseofulvum Griseofulvin
Selective toxicity
• Selective toxicity
antibiotics must be highly effective against the microbe but
have minimal or no toxicity to humans
• Therapeutic index
the ratio of the toxic dose (to the patient) to the therapeutic
dose (to eliminate the infection). The larger the index, the
safer is the drug (antibiotic) for human use.
Spektrum aktivitas
• Limited number of
Narrow microorganisms
• Penicillin: gram (+)
spectrum
• Broad range of
Broad microorganisms
• Tetracycline: gram (-), gram
spectrum (+), chlamydia, rickettsia
• Table 20.2
Aktivitas antimikroba
• Selective toxicity
• A primary factor involved in the selective toxicity:
- LPS outer layer of gram (-) bacteria
- porin  water-filled channels across this layer
• Drug that pass through the porin channels must be relatively
small and hydrophilic
• Many antibiotic that are lipophilic or especially large do not
enter gram (-) bacteria readily
• Dinding sel gram negatif - Lipopolisakarida
Penggolongan antimikroba
berdasarkan efeknya thd mikroba
Bactericidal: penicillin,
cephalosporine
Bacteriostatic:
chloramphenicol,
sulphonamide,
tetracycline
Lüllmann, Color Atlas of Pharmacology ©

2000 Thieme
Mekanisme kerja antimikroba
1. Inhibisi sintesis dinding sel
• Inhibisi sintesis peptidoglikan ddg sel  dinding sel

rapuh lisis
• Hanya dapat mempengaruhi sel-sel yang aktif
bertumbuh
• Selective
toxicity 
Antibiotik bekerja
pada dinding sel
bakteri
Beta-lactams’ mechanism of action
http://www.microbelibrary.org/images/kaiser/penresanim.gif
Vancomycin’s mechanism of action
http://www.microbelibrary.org/images/kaiser/vanresanim.gif
2. Inhibisi sintesis protein
http://www.microbelibrary.org/images/kaiser/mechanisms/altribo_antibiot.html
• Aktif pada ribosom 70S

• Mempengaruhi 50 S ribosom:
- menghambat pembentukan ikatan peptida
(chloramphenicol)
- menghambat pergerakan ribosom sepanjang mRNA
(erythromycin)
• Mempengaruhi 30 S ribosom:
- mengubah bentuk 30 S ribosom shg mRNA terbaca
salah (streptomycin, gentamicin)
- mengikat tempat perlekatan tRNA pada mRNA-
ribosom (tetracycline)
Sintesis Protein
3. Perusakan membran plasma
• Perubahan permeabilitas membran sel  hilangnya

metabolit2 penting (sitoplasma keluar dari sel)
• Polymixin B: berikatan dgn fosfolipid pada membran sel
shg permeabilitas terganggu
• Ketokonazole,amphotericin B
(Antifungi):
berikatan dgn sterol pada plasma
fungi shg terjadi kerusakan pada
membran plasma
4. Inhibisi sintesis asam nukleat
• Mempengaruhi proses replikasi dan transkripsi

DNA
• Beberapa obat dpt mempengaruhi DNA dan RNA
sel mamalia shg penggunaannya terbatas
• Rifampicin, quinolones: selective toxicity
• Rifampicin : bekerja pada RNA-polimerase 
inhibisi sintesis mRNA
• Quinolones: inhibiting DNA gyrase enzyme
(topoisomerase)  inhibiting DNA synthesis.
• Replikasi DNA
Supercoils DNA
5. Inhibisi sintesis metabolit2 penting
• Inhibitor kompetitif
• Co: gol. Sulfa dan trimetophrim
• PABA (para amino benzoic acid)  asam folat
(coenzym untuk sintesis purin dan pirimidin)
• Struktur sulfanilamide mirip dgn PABA
• m.o + sulfanilamide  asam folat tidak terbentuk
• Selective toxicity 
ANTIFUNGI
Antiviral
Antiprotozoa dan Antihelmintic
Mechanisms of resistance
1. Produce an enzyme that destroy or deactivates drug

 enzim β-lactamase
2. Slow or prevent the entry of the drug into the cell 
changes in the structure of the cytoplasmic
membrane
3. Alter the receptor for the drug
4. Alter the metabolic chemistry or abandon the
sensitive metabolic step altogether
5. Pump the drug out of the
cell before the drug can act
Antibiotics and methods of resistance
Chloramphenicol reduced uptake into cell
Tetracycline active efflux from the cell
β-lactams, Erythromycin, eliminates or reduces binding of

Lincomycin antibiotic to cell target
enzymatic cleavage or modification

β-lactams, Aminoglycosides,
to inactivate antibiotic molecule
Chloramphenicol
metabolic bypass of inhibited

Sulfonamides, Trimethoprim
reaction
overproduction of antibiotic target
Sulfonamides, Trimethoprim
(titration)
• Inherent (Natural) resistance
Bacteria may be inherently resistant to an antibiotic.
The cell wall of gram negative bacteria is covered
with an outer membrane that establishes a
permeability barrier against the antibiotic.
• Acquired resistance
Require either the modification of existing genetic
material or the acquisition of new genetic material
from another source  PLASMID: R factors
© 2009 Kenneth Todar, PhD
• Multiple resistance  superbugs
resistant to 3 or more types of antimicrobial agents
• Cross resistance
occurs when drugs are similar in structure
• Synergism effect: sulfamethoxazole - trimetophrim
• Antagonism effect: penicillin - tetracycline
UJI ANTIMIKROBA
• The Diffusion
Methods (cylinder
cup, paper
disc, well methods)
• Kirby-Bauer test
• Broth Dilution test
• MIC and MBC test
• E-test

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ANTIMIKROBA

• Tortora GJ, Funke BR, Case CL. 2001. Microbiology an

 Paul Erlich (1854-1915)

Bacillus subtilis Bacitracin

Lüllmann, Color Atlas of Pharmacology ©

• Inhibisi sintesis peptidoglikan ddg sel  dinding sel

• Aktif pada ribosom 70S

• Perubahan permeabilitas membran sel  hilangnya

• Mempengaruhi proses replikasi dan transkripsi

1. Produce an enzyme that destroy or deactivates drug

Tetracycline active efflux from the cell

β-lactams, Erythromycin, eliminates or reduces binding of

enzymatic cleavage or modification

metabolic bypass of inhibited

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