ANTIMIKROBA-Dian Natasya-

Referensi

Tortora GJ, Funke BR, Case CL. 2001. Microbiology an Introduction, 7th edition. Benjamin Cummings, San Francisco,

CA 94111, USA

Lllmann, 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 secaraselektif 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 microorganisms

Penicillin: gram (+)Narrow

spectrum

Broad range of microorganisms

Tetracycline: gram (-), gram (+), chlamydia, rickettsia

Broad spectrum

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

Lllmann, Color Atlas of Pharmacology

2000 Thieme

Bactericidal: penicillin,

cephalosporine

Bacteriostatic:

chloramphenicol,

sulphonamide,

tetracycline

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 actionhttp://www.microbelibrary.org/images/kaiser/penresanim.gif

Vancomycins mechanism of actionhttp://www.microbelibrary.org/images/kaiser/vanresanim.gif

2. Inhibisi sintesis proteinhttp://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 -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

-lactams, Erythromycin, Lincomycin

eliminates or reduces binding of

antibiotic to cell target

-lactams, Aminoglycosides, Chloramphenicol

enzymatic cleavage or modification

to inactivate antibiotic molecule

Sulfonamides, Trimethoprimmetabolic bypass of inhibited

reaction

Sulfonamides, Trimethoprimoverproduction of antibiotic target

(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