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5.1 Antimicrobial Agents

This document discusses antimicrobial agents including definitions, mechanisms of action, sources, spectrum of action, and factors influencing effectiveness. It defines terms like antibiotic, antimicrobial, bactericidal, bacteriostatic, and resistant/sensitive. It describes four main mechanisms of action: inhibiting cell wall synthesis, cell membrane function, protein synthesis, and nucleic acid synthesis. Sources include fungi, Streptomyces bacteria, and chemical synthesis. Spectrum of action can be narrow or broad. Determining antimicrobial activity involves dilution susceptibility testing.

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Wong Shuan
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129 views22 pages

5.1 Antimicrobial Agents

This document discusses antimicrobial agents including definitions, mechanisms of action, sources, spectrum of action, and factors influencing effectiveness. It defines terms like antibiotic, antimicrobial, bactericidal, bacteriostatic, and resistant/sensitive. It describes four main mechanisms of action: inhibiting cell wall synthesis, cell membrane function, protein synthesis, and nucleic acid synthesis. Sources include fungi, Streptomyces bacteria, and chemical synthesis. Spectrum of action can be narrow or broad. Determining antimicrobial activity involves dilution susceptibility testing.

Uploaded by

Wong Shuan
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
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Antimicrobial Agents

Dr. Ng Woei Kean


Ph.D. (Molecular Medicine)
Definitions
• Antibiotic: antimicrobials of microbial origin,
most of which are produced by fungi or by
bacteria of the genus Streptomyces.
• Antimicrobial: any substance with sufficient
antimicrobial activity that it can be used in the
treatment of infectious diseases.
• Bactericidal: an antimicrobial that not only
inhibits growth but is lethal to bacteria.
• Bacteriostatic: an antimicrobial that inhibits
growth but does not kill the organisms.
Bactericidal vs Bacteriostatic
• Minimal inhibitory concentration (MIC): a
laboratory term that defines the lowest
concentration (g/mL) able to inhibit growth of the
microorganism.
• Resistant: organisms that are not inhibited by
clinically achievable concentrations of a
antimicrobial agent.
• Sensitive: term applied to microorganisms
indicating that they will be inhibited by
concentrations of the antimicrobic that can be
achieved clinically.
• Spectrum: an expression of the categories of
microorganisms against which an antimicrobial
is typically active. A narrow-spectrum agent has
activity against only a few organisms. A broad-
spectrum agent has activity against organisms of
diverse types (e.g., Gram-positive and Gram-
negative bacteria).
• Susceptible: term applied to microorganisms
indicating that they will be inhibited by
concentrations of the antimicrobic that can be
achieved clinically.
Sources of Antimicrobial Agents
• Penicillin – produced by several molds of the
genus Penicillium.
• The largest source of naturally occurring
antibiotics is the genus Streptomyces, the
members of which are Gram-positive, branching
bacteria found in soils and freshwater
sediments.
• Streptomycin, the tetracyclines,
chloramphenicol, erythromycin, and many other
antibiotics were discovered by screening large
numbers of Streptomyces isolates from different
parts of the world.
• Chemically synthesized antimicrobial agents are
discovered by chance or as the result of
screening programs (e.g. sulfonamides).
• A third source of antimicrobial agents is
molecular manipulation of previously discovered
antibiotics to broaden their range and degree of
activity against microorganisms or to improve
their pharmacologic characteristics.
• E.g. penicillinase-resistant & broad-spectrum
penicillins, aminoglycosides and cephalosporins.
Spectrum of Action
• Narrow-spectrum antibiotics:
benzyl penicillin, penicillinase-
resistant penicillins, erythromycin,
clindamycin and vancomycin.
• Broad-spectrum antibiotics:
ampicillin, piperacillin,
cephalothin, ceftazidime,
imipenem, aztreonam,
tetracycline, chloramphenicol,
ciprofloxacin and etc.
Mechanisms of Action of
Antimicrobial Agents
1. Inhibition of cell wall synthesis
2. Inhibition of cell membrane function
3. Inhibition of protein synthesis
4. Inhibition of nucleic acid synthesis
Inhibition of Cell Wall Synthesis
• Antimicrobial agents: β-lactam (e.g. penicillins,
cephalosporins, carbapenems) and
glycopeptides (e.g. vancomycin).
• The peptidoglycan component of the bacterial
cell wall gives it its shape and rigidity.
• This antimicrobial agents attach to the
transpeptidases enzymes that cross-link
peptidoglycans, thus preventing cell walls
synthesis in bacteria/fungi.
• Vancomycin binds directly to the amino acids,
preventing the binding of transpeptidase.
Basic structure of β-lactam antibiotics. Different side
chains determine degree of activity, spectrum,
pharmacologic properties and resistance to β-lactamases.
Inhibition of Cell Membrane Function

• Antimicrobial agents: polypeptide antimicrobics


(e.g. polymyxin B and colistin).
• Have a cationic detergent-like effect.
• It binds to the cell membranes of susceptible
Gram-negative bacteria and alter their
permeability, resulting in loss of essential
cytoplasmic components and bacterial death.
Inhibition of Protein Synthesis

• Antimicrobial agents: Aminoglycosides (e.g.


gentamicin, streptomycin), tetracyclines,
chloramphenicol, microlides (e.g. erythromycin).
• Acts by interfering translation step in bacteria.
• Aminoglycosides – binds to bacterial ribosomes,
destabilises the ribosomes and thus prevents
elongation of polypeptide.
• Tetracyclines – blocks attachment of tRNA to
ribosomes.
• Chloramphenicol – blocks peptidyl transferase
and thus prevents peptide bond formation.
Action of antimicrobics on protein synthesis. Aminoglycosides (A) bind to multiple
sites on both the 30S and 50S ribosomes in a manner that prevents the tRNA
from forming initiation complexes. Tetracyclines (T) act in a similar manner,
binding only to the 30S ribosomes. Chloramphenicol (C) blocks formation of the
peptide bond between the amino acids. Erythromycin (E) and macrolides block
the translocation of tRNA from the acceptor to the donor side on the ribosome.
Inhibition of Nucleic Acid Synthesis

• Antimicrobial agents: quinolones (e.g.


ciprofloxacin), folate inhibitors (e.g.
sulfonamides), rifampin and etc.
• Quinolones – inhibiting DNA topoisomerase and
thus interfering DNA replication.
• Folate inhibitors - interfere with synthesis of folic
acid by bacteria and thus inhibiting nucleic acid
synthesis.
• Rifampin – blocking RNA synthesis by binding to
RNA polymerase.
Sulfonamides block
the folate precursors
of DNA synthesis,
rifampin inhibits the
synthesis of RNA
from DNA by
inhibiting RNA
polymerase, and
quinolones inhibit
DNA topoisomerase
and thus prevent the
supercoiling required
for the DNA to “fit”
inside the bacterial
cell.
Side Effects of Antimicrobial Agents

• Toxicity
• Allergy
• Disruption of normal microflora
Factors Influencing the
Effectiveness of Antimicrobial Drugs
• Drugs ability to reach the site of infection greatly
influence by the mode of administration (oral,
topical, parenteral) or exclusion from the
infected sites by blood clots, pus, necrotic
tissues.
• Susceptibility of pathogens – influenced by
growth rate and by inherent properties (has or
not the target for drugs).
• Drug concentration in the body – must exceed
the pathogens MIC.
• Drug resistance
Determining the Level of
Antimicrobial Activity
• Dilution susceptibility test: a set of broth-
containing tubes are prepared; each tube in the
set has a specific antibiotic concentration; to
each is added a standard number of test
organisms.
• The lowest concentration of the antibiotic
resulting in no microbial growth is the MIC.
• Tubes showing no growth are sub-cultured into
tubes of fresh medium lacking the antibiotic to
determine the lowest concentration of the drug
from which the organism does not recover.

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