ANTIMIKROBA -Dian Natasya-


mikrobiologi farmasi

Transcript of ANTIMIKROBA 2014

  • 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:

  • 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


    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,






  • 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



  • Antibiotik bekerja

    pada dinding sel


  • Beta-lactams mechanism of action

  • Vancomycins mechanism of action

  • 2. Inhibisi sintesis protein

    Aktif pada ribosom 70S

    Mempengaruhi 50 S ribosom:

    - menghambat pembentukan ikatan peptida


    - menghambat pergerakan ribosom sepanjang mRNA


    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


    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


  • 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


    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


    Sulfonamides, Trimethoprimoverproduction of antibiotic target


  • 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


    The Diffusion Methods (cylinder

    cup, paper

    disc, well methods)

    Kirby-Bauer test

  • Broth Dilution test

    MIC and MBC test

  • E-test