Baedah Madjid

BAGIAN MIKROBIOLOGI FK-UNHAS

2007

A. Antibiotics & antibacterial agent

a. Antibiotics: Produced only by
microorgnisms (Natural)
b. Antibacterials: Produced: natural, synthetics
or semi-synthetics
B. Bacteriostatic agents & Bactericidal agents
C. Narrow-spectrum & Broad-spectrum
antibacterial agents
D. MIC & MBC

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

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
a. Natural penicillins
Penicillin G

b. Semisynthetics
penicillins
Methicillin, oxacillin,
cloxacillin, nafcillin,
discloxacillin

c. Extended-spectrum

penicillins (Broad-s)

a. Aminopenicillin:
ampicillin, amoxycillin
b. Carboxypenicillin:
carbenicillin, ticarcillin
c. Ureidopenicillins:
azlocicllin
d. Piperazine penicillin:
piperacillin

Penicillins
1.

Mechanism of action

3.

Target:penicillin-binding
proteins transpeptidase,
carboxypeptidase,
autolytic enzymes
Inactivation of than enzymes
rapid dest-ruction of
peptidoglycan & dissulution
cell wall bacterial lysis

2.

Spectrum
a. Natural Penicillin
Narrow : Gr + &
anaerob
b. Semi-synthetics
-lactam ring << <
accessible
c. Extended-spectrum P
Gr+ & Gr
Some: have -lactamase
inhibitors

Bacterial resistance
-lactamases

4.

Toxicity
very limited

Cephalosporins
Classification
a.
b.
c.

First-generation : Oral & injectible form

Second-generation : mostly injectible
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

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 ( R ) plasmids
- New chromosomal genes

Mechanisms of Bacterial Resistance

A.
B.
C.
D.
E.

Enzymatics inactivation
Modification of cell wall permiability
Alteration of target molecules
Development of alternate pathways
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, nucleotidases: modify aminoglycosides incapble of

binding to the ribosomal target.

3. Chloramphinecol acetyltransferases: similar

to aminoglycoside transferases.

B. Modification of cell wall permiability

Degree of cell wall permeability correlates w
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. R 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.

ANTIBACTERIAL
Penicillin
Cephalosporin

RESISTANCE MECHANISMS

& Enzymatic inactivation (-lactamase)

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
protein)

Chloramphenicol

Enzymatic inactivation (acetyltrans-ferase)

Macrolides

Target alteration (50S ribosomal unit)

Quinolones

Target alteration (DNA gyrase mutation)

(mutation of membrane transport