Download Dr.A.K.AL-Yassari 2016-2017 Microbiology Year:third Antibiotics

Dr.A.K.AL-Yassari
2016-2017
Microbiology
Year:third
Antibiotics and Chemotherapeutic agents
 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.
 Chemotherapeutic: a broad term that encompasses antibiotics, antimicrobials, and
drugs used in the treatment of cancer. In the context of infectious diseases, it implies
the agent is not an antibiotic.

Resistant: organisms that are not inhibited by clinically achievable concentrations of
a antimicrobial agent.
 Sensitive or Susceptible: term applied to microorganisms indicating that they will be
inhibited by concentrations of the antimicrobial that can be achieved clinically.
 Narrow-spectrum antibiotics: chemotherapeutic agents acting only on a single or a
limited group of microorganisms are said to have a narrow spectrum. For example,
isoniazid is active only against Mycobacteria.
 Extended-spectrum antibiotics: is the term applied to antibiotics that are effective
against gram-positive organisms and also against a significant number of gramnegative bacteria. Cephalosporins generation are a good example.
 Broad-spectrum antibiotics: drugs such as tetracycline and chloramphenicol affect a
wide variety of microbial species (G+ and G- bacteria) and are referred to as broadspectrum antibiotics.
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Dr.A.K.AL-Yassari
2016-2017
Microbiology
Year:third
Factors effecting individuality of the ideal antimicrobial drug:
1. Selective toxicity to the microbe but non-toxic to host cells.
2. Microbicidal rather than microbistatic.
3. Relatively soluble and functions even when highly diluted in body fluids.
4. Remains potent long enough to act and is not broken down or excreted prematurely.
5. No subject to development of antimicrobial resistance.
6. Complements or assists the activities of the host's defenses.
7. Remains active in tissues and body fluids.
8. Readily delivered to the site of infection.
9. Not excessive in coast.
10.Doesn't disrupt the host's health by causing allergies or predisposing the host to other
infection.
Classification of antibiotics:
According to the mode of action:
1.
2.
3.
4.
5.
Inhibition of cell wall synthesis: such as penicillin, cephalosporin, and vancomycin.
Inhibition of cell membrane function: such as polymyxin, and colistin.
Inhibition of protein synthesis: such as tetracycline, aminoglycoside, and macrolides
Inhibition of nucleic acid synthesis: such as quinolones, rifampin, and metronidazole.
Inhibition of essential metabolites: such as sulphonamides, and trimethoprim.
According to the spectrum:
A. Narrow spectrum: such as penicillin which effect on G+ bacteria, and colistin which
effect on G- bacteria.
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Dr.A.K.AL-Yassari
2016-2017
Microbiology
Year:third
B. Extended spectrum: antibiotics which have had chemical modifications which increa
their gram negative coverage. An example is the first generation of cephalosporins
have no effect on gram negative bacteria, while in the next generations cephalosporins
will be active against gram negative bacteria.
C. Broad spectrum: effect on G+ and G- bacteria such as tetracycline and
chloramphenicol.
According to their action:
 Bacteriostatic: such as macrolides and sulphonamides.
 Bacteriocidal: such as penicillin and amoxicillin.
According to their absorption degree:
1. Weak absorption: useful in enteric infections such as neomycin and streptomycin.
2. Middle absorption: useful in enteric and systemic infections such as sulphonamides.
3. Strong absorption: useful in systemic infections such as erythromycin.
Mechanisms of antibiotics action:
 Inhibition of cell wall synthesis
 Binding to penicillin binding proteins (PBPs) These penicillin-binding proteins
(PBPs) are bacterial enzymes involved in the synthesis of the cell wall and in the
maintenance of the morphologic features of the bacterium.
 Inhibition of transpeptidase: Some PBPs catalyze formation of the cross-linkages
between peptidoglycan chains. Penicillins inhibit this transpeptidase-catalyzed
reaction, thus hindering the formation of cross-links essential for cell wall integrity.
 Production of autolysins which are degradative enzymes causing cell lysis.
 Binding to the D-Ala-D-Ala side chain in cell wall and This prevents the
transglycosylation step in peptidoglycan polymerization, thus weakening the cell wall
and damaging the underlying cell membrane.
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Dr.A.K.AL-Yassari
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2016-2017
Microbiology
Year:third
Inhibition of cell membrane function
Alters bacterial outer membrane permeability by binding to a negatively charged site
in the lipopolysaccharide layer, the result is a destabilized outer membrane.
Fatty acid portion dissolves in hydrophobic region of cytoplasmic membrane and
disrupts membrane integrity.
Leakage of cellular molecules, and inhibition of cellular respiration.
Binds and inactivates endotoxin.
Inhibition of protein synthesis
 Tetracyclines bind reversibly to the 30S subunit of the bacterial ribosome, thereby
blocking access of the amino acyl-tRNA to the mRNA-ribosome complex at the
acceptor site. By this mechanism, bacterial protein synthesis is inhibited.
 Aminoglycosides bind to the 30S ribosomal subunit prior to ribosome formation cause
the 30S subunit of the completed ribosome to misread the genetic code.
 Macrolides bind irreversibly to a site on the 50S subunit of the bacterial ribosome,
thus inhibiting the translocation steps of protein synthesis.
 Chloramphenicol bind to the bacterial 50S ribosomal subunit and inhibits protein
synthesis at the peptidyl transferase reaction.
Inhibition of nucleic acid synthesis
 The quinolones and novobiocin act on enzymes which separate the strands of DNA
during bacterial replication such as DNA gyrase (in Gram-negative bacteria) and
topoisomerase IV (more commonly in Gram- positive organisms).
 Rifampin acts by interfering with the activity of RNA polymerase, and preventing
RNA synthesis.
 Metronidazole, the most commonly used drug of the nitroimidazole class, causes
breaks in DNA strands.
Inhibition of essential metabolites
 Sulphonamides interfere with the formation of folic acid, an essential precursor for
nucleic acid synthesis.
 Trimethoprim, inhibits the activity of dihydrofolate reductase which an essential
enzyme in the synthesis of folic acid by bacteria.
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Dr.A.K.AL-Yassari
2016-2017
Microbiology
Year:third
Antibiotics classification according to their mode of action
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Dr.A.K.AL-Yassari
2016-2017
Microbiology
Year:third
Modes and sites of action of antibacterial drugs
Factors influencing antibacterial activity
1.
2.
3.
4.
5.
Site and rate of absorption.
The site of excretion.
The tissue distribution and metabolism.
Drug–pathogen interactions.
Host-pathogen interaction.
Antibiotics combinations
When antibacterial drugs are combined for the treatment of disease, the outcome is
influenced by the particular combinations used:
1. A synergistic effect results when the combined action of two drugs is significantly
greater than the sum of effects of each drug used separately.
2. Indifference is defined as lack of an enhancement effect when two drugs are
administered in combination.
3. Antagonism describes the reduced effectiveness of combined antibacterial therapy
when compared with the effectiveness of each drug alone.
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Dr.A.K.AL-Yassari
2016-2017
Microbiology
Year:third
Antibiotics resistance
 Intrinsic resistance due to an inherent characteristics of the microorganisms. For
example, gram-negative organisms are inherently resistant to vancomycin.
 Acquired resistance : resistance that develops through mutation or acquisition of
new genes.
Mechanisms of antibiotic resistance
1. Enzymatic destruction of drug, an example β-lactamase (penicillinases).
2. Prevention of penetration of drug.
3. Alteration of drug's target site.
4. Rapid ejection of the drug by using pump efflux.
5. A variety of mutations can lead to antibiotic resistance. An example is the emergence
of rifampin-resistant Mycobacterium tuberculosis when rifampin is used as a single
antibiotic.
6. Resistance genes are often on plasmids or transposons that can be transferred between
bacteria by conjugation, transduction and transformation processes, finally lead to
antibiotic resistance.
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Dr.A.K.AL-Yassari
2016-2017
Mechanisms of antibiotics resistance
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Microbiology
Year:third