ANTIMICROBIALS

AGENTS

Setio Harsono
Dept/SMF Mikrobiologi Klinik
FK Unair/RSUD.Dr.Soetomo

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 Desirable Properties :

1. Selective toxicity
2. Bactericidal
3. Susceptible organisms do not become resistant
4. Effective againts a broad range of microorganisms
5. Should not be allergenic
6. Should not cause adverse side effect
7. Should remain active in the presence of plasma, body
fluids, or exudates
8. Water soluble and stable
9. Bactericidal levels in the body be rapidly reached and
maintained for prolonged periods
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Definitions :
 Bactericidals = kills the organisms againts which
they are used.
 Bacteriostatic = inhibitory to the organisms and
relys upon the host defence mechanisms for final
eradications.

Antimicrobials drug used in combinations

1. Prompt treatment of unknown pathogens.
2. Mixed infections.
3. Delay emergence of resistant mutants.
4. Synergism.
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Adverse effect :
1. Toxic side effect.
2. Development of hypersensitivity.
3. Mask serious infection without eradicating
pathogens.
4. Alteration of normal flora.

MECHANISMS OF ACTION :
1. Cell Wall Inhibitors.
• Penicillin Cephalosporin Fosfomycin.
• Vancomycin Bacitracin.
2. Cell Membrane Inhibitors
Polymyxins 4
3. Inhibitors of Proteins Synthesis and Assembly.
• Inhibitors of Transcription :
● Rifampicin ● Actinomycin
• Inhibitors of Translation
● Inhibitors of the 30S Ribosomal Subunit.
- Aminoglycosides - Nitrofurans - Tetracyclin
● Inhibitors of the 50S Ribosomal Subunit.
- Chloramphenicol - Lincomycin and Clindamycin
- Fusidic Acid - Erythromycin
• Inhibitors of Protein Assembly.
● Griseofulvin.
4. Inhibitors of DNA Function.
• Quinolones
• Novobiocin
• Metronidazole
• Mitomycin

5. Metabolite Analogues.
• Sulfonamides, Trimethoprim, Isoniazid, PAS, Sulfones, Flucytosine.
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Antimicrobial Action 7
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 MECHANISMS OF ANTIMICROBIAL
RESISTENCE
1. Decreased Cell Permeability.
• Tetracyclines Resistance.
2. Enzymatic Inactivation of the Antimicrobials.
• Inactivation of Beta-Lactam Antibiotics.
• Inactivation of Aminoglycosides Antibiotics.
• Inactivation of Chlorampenicol.
3. Modification of Antimicrobials Receptor side.
• Streptomycin Resistance.
• Erythromycin Resistance.
• Rifampicin Resistance.
• Penicillin Resistance.
4. Synthesis of Resistance Pathway.
• Sulfonamide Resistance.
• Trimethoprim Resistance.
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Resistensi bakteri terhadap Antimikroba
1. Non Genetik
• Bakteri yang proses metabolismenya tidak aktif 
resisten terhadap antimikroba.
Misal : Mycobacterium yang tidak mengadakan
multiplikasi dalam sel inang (Dormant)  resisten
terhadap Antimikroba.
• Bakteri kehilangan target spesifik untuk Antimikroba.
Misal : Bakteri L-form karena tidak mempunyai dinding
sel  Resisten terhadap Penicillin / Cephalosporin.
2. Genetik
Mikroorganisme sering resisten terhadap Antimikroba 
karena adanya perubahan genetik.

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Perubahan Genetik
● Chromosome
● Extra Chromosome

Chromosome Resistance
Terjadi karena Mutasi spontan  perubahan struktur
receptor untuk antimikroba.
Misal : Perubahan receptor spesifik pada Ribosome.

Extra Chromosome Resistance

Bakteri mempunyai elemen genetik extra chromosome
letak didalam cytoplasma  disebut Plasmid.
R-factor  Plasmid yang mengatur resistensi terhadap
antimikroba 12
Elemen Genetik dapat ditransfer dari satu sel
bakteri ke sel bakteri lain

● Transduksi
Misal : Staphylococcus  plasmid ß – lactamase
● Transformasi
Misal : H. influenzae
● Conjugasi
Misal : Bakteri Gram negatif  melalui Pili

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Resistant Gene Transfer 14
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 UJI KEPEKAAN
ANTIMIKROBA
Implikasi Klinis Pemakaian Antimikroba
• Pemakaian antimikroba  terjadi seleksi  kuman
resisten berkembang biak kuman sensitif akan mati /
punah.
• Kuman patogen  banyak yang resisten  untuk terapi
penderita yang tepat  perlu dilakukan Uji Kepekaan
Antimikroba.

Tujuan Uji Kepekaan Antimikroba :

Mengetahui apakah kuman yang diisolasi dari penderita
masih sensitif atau sudah resisten terhadap antimikroba
tertentu. 16
Jenis pemeriksaan :
1. Pemeriksaan Kwalitatif
 Mengetahui kuman sensitif / resisten terhadap
antimikroba.
2. Pemeriksaan Kwantitatif
Mengetahui kuman sensitif / resisten terhadap
antimikroba.
Mengetahui berapa konsentrasi antimikroba yang dapat
menghambat atau membunuh kuman.

Pemeriksaan Kwalitatif :
Cara : Uji Difusi
Metode : 1. Agar disk diffusion (metode Kirby-Bauer).
2. Agar wells diffusion.
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Pemeriksaan Kwantitatif :
Cara : Uji Dilusi
Metode : 1. Agar dilution.
2. Broth dilution : - Micro dilution test.
- Macro dilution test.

Uji Kepekaan Kuman Anaerob :

Cara : Uji Dilusi
Metode : 1. Agar dilution.
2. Broth dilution : - Micro dilution test.
- Macro dilution test.
Cara : Uji Elusi
Metode : Broth-Disk elution.

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Menurut Standard CLSI (Clinical and Laboratory Standards Institute)
Metode : Agar disk diffusion
1. Medium: Mueller-Hinton agar
2. Inokulum kuman: 0,5 Mc Farland standard ~ 1,5 x 10 8kuman/ml
3. Disk content: - Penicillin = 10 units - Chloramphenicol = 30 µg
- Tetracycline = 30 µg - Erythromycin = 15 µg
- dll.
4. Inkubasi: 35 ± 2º C, ambient air, 16 – 18 jam
Mc Farland Nephelometer Standard :
0,5 1 2 3 4 5
Barium Chloride (mL) 0,05 0,1 0,2 0,3 0,4 0,5
Sulfuric Acid (mL) 9,95 9,9 9,8 9,7 9,6 9,5
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Approx. Cell Density 1,5 3 6 9 12 15
(x 10 / mL)
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• Scheme of Broth Dilution 22
Pemeriksaan Broth Dilution: Macro Dilution Test 23
Pemeriksaan Broth Dilution: Micro Dilution Test 24