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 c. Extended-spectrum
a. Natural penicillins penicillins (Broad-s)
Penicillin G a. Aminopenicillin:
ampicillin, amoxycillin
b. Semisynthetics
b. Carboxypenicillin:
penicillins
carbenicillin, ticarcillin
Methicillin, oxacillin,
cloxacillin, nafcillin, c. Ureidopenicillins:
discloxacillin azlocicllin
d. Piperazine penicillin:
piperacillin
Penicillins
1. Mechanism of action 3. Spectrum
Target:penicillin-binding a. Natural Penicillin
proteins transpeptidase, Narrow : Gr + &
carboxypeptidase, anaerob
autolytic enzymes b. Semi-synthetics
Inactivation of than enzymes -lactam ring << <
rapid dest-ruction of accessible
peptidoglycan & dissulution
cell wall bacterial lysis c. Extended-spectrum P
Gr+ & Gr
2. Bacterial resistance
Some: have -lactamase
-lactamases inhibitors
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
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. 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 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 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)