POTENSI

DAN
RESISTENSI ANTIBIOTIK

Muhamad Rinaldhi Tandah

Program Studi Farmasi
Fakultas Matematika dan Ilmu Pengetahuan Alam
Universitas Tadulako
Palu
ANTI BACTERIAL AGENTS
A. Antibiotics & antibacterial agent
B. Bacteriostatic agents & Bactericidal
agents
C. Narrow-spectrum & Broad-spectrum
antibacterial agents
D. MIC & MBC
ANTI BACTERIAL AGENTS
A. Antibiotics & antibacterial agent
a. Antibiotics: Produced only by
microorgnisms (Natural)
b. Antibacterials: Produced: natural, synthetics
or semi-synthetics

B. Bacteriostatic agents & Bactericidal agents

. Bacteriostatic agents: inhibit the growth of
microorganisms
. Bactericidal agents: kill microoranisms
ANTI BACTERIAL AGENTS
C. Narrow-spectrum & Broad-spectrum
antibacterial agents
. Narrow-spectrum antibacterial agents:
effective againts only a limited range of
organisms
. Broad-spectrum antibacterial agents:
effective againts wide range of organisms

D. MIC (Minimal Inhibitory Concentration) &

MBC (Minimal Bactericidal

Concentration)
 Antibiotics
Properties of antibiotics we need:

Prevent the bacterial multiplication or can

destroy pathogen bacteria, but not the host
cells.
Bactericidal agents >> Bacteriostatic agents
The bacteria still sensitive
Effective to many bacteria
Do not cause allergy or other side effect.
Active in plasma or other body liquid.
Stable in solution.
 Criteria for Effective Antibiotic Action
1. Microorganism : a unique & vital target
susceptible to C must exist in microorganism,
target must differ from related host target
side effects
2. Antibacterial Agents
a. Able to penetrate the bacterial surface &
reach target of its action.
b. Can reach the infected tissue
c. Can not diffuse in to mammalian cells
3. Host
a. Intact immune system
b. vascularization & drainage
Antibiotics Rational Therapy
Rational Therapy:
Appropriate target, dose, regimens, and application.

For Rational Antibiotic Therapy: we must know

1. Microbiology : The agents & its susceptibility
2. Clinical: organs or tissue involved the
antibiotics must be rapidly reached the tissue &
still in active condition
3. Pharmacology: Pharmacokinetic &
Pharmacoaction: solubility, toxicity, side effects
 CLASSIFICATION
Antibacterial agents that inhibit:
A. Cell wall synthesis
1. -lactam antibacterial agents
2. Other inhibitors of bacterial cell wall
synthresis
B. Nucleotide synthesis
C. Nucleic acid synthesis
1. DNA synthesis inhibitors
2. RNA synthesis inhibitors
D. Protein synthesis
1. Inhibitors of the 30S ribosomal unit
2. Inhibitors of the 50S ribosomal unit
A. Antibacterial agents that inhibit cell wall
synthesis

1. -lactam antibacterial agents

Inhibition of peptidoglican layer cross-
linking:
- Penicillin
- Cephalosporin
- Others: carbapenems (e.g. imipenem),
monobactam (e.g. aztreonam)
2. Other inhibitors
Inhibition of peptidoglican synthesis:
- Cyclocerine
- Vancomycin
- Bacitracin
 Penicillins
Classification
c. Extended-spectrum
a. Natural penicillins
Penicillin G
b. Semisynthetics penicillins
Methicillin, oxacillin,
cloxacillin, nafcillin,
discloxacillin
penicillins (Broad-s)
a. Aminopenicillin:
ampicillin, amoxycillin
b. Carboxypenicillin:
carbenicillin, ticarcillin
c. Ureidopenicillins:
azlocicllin
d. Piperazine penicillin:
piperacillin
Penicillins
1. Mechanism of action 3. Spectrum
Target:penicillin-binding a. Natural Penicillin
proteins transpeptidase, Narrow : Gr + & anaerob
carboxypeptidase, b. Semi-synthetics
autolytic enzymes -lactam ring << <
Inactivation of than enzymes accessible
rapid destruction of
peptidoglycan & dissulution cell c. Extended-spectrum P
wall bacterial lysis Gr+ & Gr
Some: have -lactamase
2. Bacterial resistance inhibitors
-lactamases
4. Toxicity
very limited
Cephalosporins
Classification
a. First-generation : Oral & injectible form
b. Second-generation : mostly injectible
c. Third-generation: mostly injectible
d. Fourth-generation: mostly injectible

Spectrum: broad-spectrum
Toxicity :
- Allergy
- More toxic than penicillin nephrotoxic
- Latest generation < toxic than early-generation
B. Antibacterial agents that inhibit
nucleotide synthesis
1. Sulfonamides
a. Preparations: Sulfadiazine, sulfamethoxazole,
sulfisoxazole, sulfaamethoidiazine orally.
b. Mechanism of action: bacteriostatic conpetitive to
PABA
c. Spectrum: broad
d. Toxicity: Hypersensitivity
hematologic disorders & crystal formation
2. Trimethoprim structure = hydrofolic acid

3. Sulfamethoxazole-trimethoprim
synergic combination.
C. Antibacterial agents that inhibit
nucleic acid synthesis
1. DNA synthesis inhibitors
a. Novobiocin : limited clinical use
b. Quinolones:
Nalidixic acid : brod spcetrum UT
Flouroquinolones: cloxacin, ciprocloxacin
derivate
of naidixic acid , orally & parenterally.
c. Nitromidazoles, Metronidazole.
Spectrum: T. vaginalis, G. lamblia, E. histolytica,
obligate anaerobic.
Toxicity: mutagenic

2. RNA synthesis inhibitors

Rifampicin : M. tbc, M. leprae, Legionella,
meningitis (N. meningitidis, H. influenzae)
D. Antibacterial agents that inhibit
Protein synthesis
1.Inhibitors of the 30S ribosomal unit
a. Aminoglycosides
- Streptomycin: 2nd line anti-tbc, injection
- Neomycin: topical. orally
- Kanamycin: primary used as anti-tbc
- Gentamycin, tobramycin, amikasi, netilmycin:
fewer bacteria R
b. Tetracyclines: broad-spectrum
2. Inhibitors of the 50S ribosomal unit
a. Chloramphenicol: typhoid fever, H. influenzae,
rickettsia
b. Macrolide antibiotics: erythromycin,
azithromycin
c. Lincosamides: lincomycin, clindamycin
Contoh Hasil Uji Potensi Antibiotik
 T S
EN
AG
A L
R I
T E
AC
I B
T
AN
TO
C E
AN
IS T
E S
R
RESISTANCE TO ANTIBACTERIAL AGENTS
Acquisition of bacteral resistance
A. Intrinsic resistance
related to bacterial structure feature
(permiability of bacterial cell wall)
determined by chromosomal gene. e.g.
Pseudomonas aeroginosa.
B. Mutational resistance
related to chromosomal mutation unable
to interact with antibacterial.

C. Acquisition of resistance genes

- Resistance plasmids
- New chromosomal genes
Mechanisms of Bacterial Resistance

A. Enzymatics inactivation
B. Modification of cell wall permiability
C. Alteration of target molecules
D. Development of alternate pathways
E. Active exclusion of the antimicrobial agent
from the bacteria
F. Development of tolerance
A. Enzymatic inactivation of antibacterial
agents
1. -lactamases: hydrolize -lactam ring of
penicilin

2. Acetyltranferases, phosphorylases,
nucleo-tidases: modify aminoglycosides
incapable of binding to the ribosomal target.

3. Chloramphinecol acetyltransferases:
similar to aminoglycoside transferases.
B. Modification of cell wall permeability
Cell wall permeability correlates with intrinsic resistance
1. Purin (specific outer membrane protein in Gr-negative)
Mutation affecting purin inhibit transport >>> AB.
2. Lipopolisaccharida (LPS) inhibit passage of
hydrophobic antibacterial agents throuh the cell wall.
Thus mutans which lack polysaccharide capsule and
minimal LPS more permiable to multiple antibiotics
3. Membrane transport proteins. Mutation of mtp
resistance to tetracyclin as a result of
transportation into cell
4. Electron transports. Uptake aminoglycosides depens
on electron transport to oxygen this agents are not
effective to anaerobic bacteria or to facultative
organisms in anaerobic enviroment (e.g. abscess)
C. Alteration of target molecules. Molecule target may
be located on cytoplasmic (e.g. PBP), or inside the
cytoplasic membrane (e.g. ribosome). Alteration of the
target affnity for the antibacterial compound.

D. Development of alternate pathways. A mutant

enzyme may bypass the synthetic block exerted by
antibiotic by using an alterntivepathway.

E. Active exclusion of the antimicrobial agent from

the bacteria. Resistance to tetracyclin is mediated by the
synthesis new transport proteins that actively exluded
the drug.

F. Development of tolerance. Impermiability outer

membrane & inactivation of murein hydrolases (autolytic
enzymes) renders bactericidal agent to bacteriostatic.
 BACTERIAL RESISTANCE
ACCORDING TO DRUG CLASS
ANTIBACTERIAL RESISTANCE MECHANISMS
Penicillin & Enzymatic inactivation (-lactamase)
Cephalosporin Target modification (PBPs)
Tolerance

Sulfonamides Active exclusion

Target alternation
Aminoglycosides Enzymatic inactivation (acetyltrans-ferase, phosphorilase,
nucleotidases)
Target alteration (30S ribosomal unit)
Decriaced cell wall permiability

Tetracyclines Active exclusion (mutation of membrane transport

protein)
Chloramphenicol Enzymatic inactivation (acetyltrans-ferase)
Macrolides Target alteration (50S ribosomal unit)
Quinolones Target alteration (DNA gyrase mutation)
ES RESISTENSI TERHADAP ANTIBIOTIK

A.Diffusion Test:
Disc Diffusion test
B. Dilution test:
Tube Dilution test
Microbroth Panel Dilution Test
C. Combine : E. Susceptibility Test
ES RESISTENSI TERHADAP ANTIBIOTIK

Disc Diffusion test: E. Test susceptibility

- R or S MBC & MIC
ES RESISTENSI TERHADAP ANTIBIOTIK
MBC: Minimal Bactericidal Concentration
MIC: Minimal Inhibitory Concentration

Microbroth Panel Test

MBC & MIC