antibiotics of microbilogy syllabls

1. Antimicrobial agents

2. Principles and Definitions
• Antimicrobial drugs frequently play a role in the treatment of
both purulent and mucosal infection in the head and neck
region
• Antimicrobial agents may also be used prophylactically for
example in the prevention of infective endocarditis among
susceptible patients receiving dental treatment.
– The ideal antimicrobial agent
3. Selective toxicity against microbial target
4. Minimal toxicity to the host
5. Cidal activity
6. Long plasma half life
7. Good tissue distribution
8. Oral and parenteral preparation
9. No adverse interactions with other drugs

3. Principles and Definitions
• Antibiotic are natural product of bact. or fungi which kill or inhibit the
growth of other micro-orginisms
• Most of antimicrobial drugs in current use have been chemically
modified.
• classification
Bactericidal; agents KILL bacteria.
• Bacteriostatic; agents INHIBIT GROWTH of bacteria
• Target site
6. Cell wall synthesis 3. nucleic acid synthesis
7. Protein synthesis 4. membrane function

4. Principles and Definitions
• Combination therapy
– Prevent emergence of resistant strains
– Take advantage of antibiotic synergism
• Penicillins and aminoglycosides inhibit cell wall
synthesis and allow aminoglycosides to enter the
bacterium and inhibit protein synthesis.
• CAUTION: Antibiotic antagonism
– Penicillins and bacteriostatic antibiotics. Cell wall
synthesis is not occurring in cells that are not growing.
– Susceptibility tests are a valuable aid to antibiotic
management of infection. There are tow main types;
diffusion tests and dilution tests.

5. Antibiotic that inhibit cell-wall
synthesis
• BETA-LACTAMS
Includes the penicillins and cephalosporins
Structurally these agents all contain the beta-lactam ring
• Mode of action
• They prevent cell wall synthesis by binding to the enzyme
known as penicillin binding proteins which are responsible
for the final stages of cross-linking of the cell wall during
growth and division.
• Many are active against G+ve bacteria.
• New beta-lactum with activity against G-ve bacteria.
• Some patients are allergic to beta-lactum antibiotic

6. Antibiotic that inhibit cell-wall
synthesis
• GLYCOPEPTIDS
• Include vancomycin and teicoplanin
Mode of action
• Interfere with cell wall synthesis by binding to terminal D-
ala-D-ala residue at the end of pentapeptide chains.
• This prevents the subsequent incorporation of new
subunits into growing cell wall.
• They are active against G+ve bacteria.

7. Review of Initiation of Protein Synthesis
1 3
30S 2 GTP
1 2 3 GTP
Initiation Factors
f-met-tRNA
mRNA
Spectinomycin
3
GDP + Pi
2
50S
P A
1 1
2 GTP
70S Aminoglycosides
30S
Initiation Initiation
Complex Complex

8. Review of Elongation of Protein Synthesis
P A Tetracycline P A
Tu GTP Tu GDP + Pi
GTP Ts
Ts Tu
Ts GDP
Chloramphenicol
GDP
Fusidic Acid +
GTP
G
G GDP + Pi
G GTP
P A P A
Erythromycin

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Inhibitor of protein synthesis
Aminoglycosides
(only bactericidal protein synthesis inhibitor)
streptomycin, kanamycin, gentamicin, tobramycin,
amikacin, netilmicin, neomycin (topical)
• Modes of action -
– Irreversibly bind to the 30S initiation complex (30S-mRNA-
tRNA) and prevents initiation of translation.
– must be given I.V or I.M.
– Their main indication is for treatment for serious G-ve
infection.
– They are potentially nephrotoxic & ototoxic.
– They are not indicated for the treatment of oral and dental
infection.

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Tetracyclines (bacteriostatic)
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tetracycline, minocycline and doxycycline
• Mode of action - The tetracyclines reversibly bind to the 30S
ribosome and inhibit binding of aminoacyl-t-RNA to the acceptor site
on the 70S ribosome.
• Spectrum of activity - Broad spectrum; Useful against intracellular
bacteria (chlamydiae)
• Resistance – Common
• Tetracycline mouthwashes sometimes used for treatment of oral
ulceration
• Adverse effects - Destruction of normal intestinal flora resulting in
increased secondary infections (Candida spp.); staining and
impairment of the structure of bone and teeth. Not used in children.

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Chloramphenicol,
Lincomycin, Clindamycin
(bacteriostatic)
• Mode of action - These antimicrobials bind to the 50S ribosome and
inhibit peptidyl transferase activity. No new peptide bonds formed.
• Spectrum of activity - Chloramphenicol - Broad range;
Lincomycin and clindamycin - Restricted
range
It used for the prophylaxis of infective endocarditic in patients who are
allergic to penicillin.
• Resistance - Common
• Adverse effects - Chloramphenicol is toxic (bone marrow
suppression) but is used in life threatening situations such as the
treatment of bacterial meningitis.

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Macrolides (bacteriostatic)
erythromycin, clarithromycin, azithromycin, spiramycin
• Mode of action - The macrolides inhibit translocation of
the ribosome.
• Spectrum of activity - Gram-positive bacteria,
Mycoplasma, Legionella
• Resistance - Common

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Fusidic acid (bacteriostatic)
• Mode of action - Fusidic acid binds to elongation factor G (EF-G) and
inhibits release of EF-GDP from the EF-G/GDP complex. Can’t
reload EF-G with GTP.
• Spectrum of activity - Gram-positive cocci
• Topical preparation including an ointment for treatment of angular
cheilitis.
• Main use is in the treatment of staphylococcal infection resistant to
beta-lactum or in penicillin-allergic patients

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inhibitor of nucleic acid
Rifampin, Rifamycin,
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Rifampicin, Rifabutin
(bactericidal)
Mode of action - These antimicrobials bind to RNA polymerase and
inhibit of mRNA synthesis.
• Spectrum of activity - Broad spectrum but is used most commonly in
the treatment of tuberculosis.
• Resistance - Common. Develops rapidly (RNA polymerase
mutations)
• Combination therapy - Since resistance is common, rifampin is
usually used in combination therapy to treat tuberculosis.

15. Quinolones (bactericidal)
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nalidixic acid, ciprofloxacin, ofloxacin,
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norfloxacin, levofloxacin, lomefloxacin,
sparfloxacin
• Mode of action - These antimicrobials inhibit an enzyme called DNA
gyrase and prevent supercoiling of DNA, thereby inhibiting DNA
synthesis.
• Spectrum of activity - Gram-positive cocci and urinary tract
infections
• The commonest side-effects are gastrointestinal.
• METRONIDAZOLE; the active intermediates of the drug
interact with and break the bacterial DNA
• It is active against anaerobic bacteria
• It is widely used by dentists.

16. Inhibitors of Folic Acid Synthesis
• Basis of Selectivity- p-aminobenzoic acid + Pteridine
Bacteria synthesize Sulfonamides
Pteridine
folic acid, humans synthetase
do not. We get it Dihydropteroic acid
from our diet.
Dihydrofolate
• Review of Folic synthetase
Acid Metabolism
Dihydrofolic acid
• Tetrahydrofolate
Dihydrofolate
required for the Trimethoprim reductase
methyl group on
methionine, and for Tetrahydrofolic acid
thymidine and purine Thymidine Methionine
synthesis. Purines

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Sulfonamides,
Sulfones
(bacteriostatic)
• Mode of action - These antimicrobials are analogues of para-
aminobenzoic acid and competitively inhibit dihydropteroate synthetase,
block the formation of tetrahydrofolic acid and inhibits synthesis of
purines and pyrimidine
• Spectrum of activity - Broad range activity against gram-positive and
gram-negative bacteria; used primarily in urinary tract and Nocardia
infections.
• Resistance - Common
• Combination therapy - The sulfonamides are used in combination with
trimethoprim; this combination blocks two distinct steps in folic acid
metabolism and prevents the emergence of resistant strains.

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Trimethoprim,
Methotrexate,
Pyrimethamine
(bacteriostatic)
• Mode of action - These antimicrobials binds to dihydrofolate
reductase and inhibit formation of tetrahydrofolic acid.
• Spectrum of activity - Broad range activity against gram-positive and
gram-negative bacteria; used primarily in urinary tract and Nocardia
infections.
• Resistance - Common
• Combination therapy - These antimicrobials are used in combination
with the sulfonamides; this combination blocks two distinct steps in
folic acid metabolism and prevents the emergence of resistant strains.

19. Antifungal agents
Most act on synthesis or function of the fungal cell membrane.
• POLYENES
Includes nystatin & amphotericin B
Mode of action; bind to sterol in eukaryotic cell membranes resulting in
impairment of barrier function.
Spectrum of activity- amphotericin B;broad spectrum but is very toxic.
Used in treatment of systemic mycosis.
New formalation of amphotericin B (AmBisome) is better tolerated. Used
for treatment of oral candidosis
Nystatin; prescribed for topical use.

20. Antifungal agents
• AZOLES
Includes fluconazole, itraconazol and miconazole
• Mode of action- bind to cytochrome P450 which lead to
inhibition of lanosterol C14-demethylase resulting in
inhibition of ergosterol synthesis
• Spectrum activity- fluconazole ; oropharyngeal
candidosis
Resistance- common
Itraconazole; broad spectrum

21. Antiviral agents
• ACICLOVIR- is the only one likely to be prescribed by
dental surgeons
• Mode of action- inhibition of herpesvirus DNA
polymerase, and lead to DNA chain termination
It is an analogue of guanosine
• Spectrum activity- herpes simplex virus
It is valuable in the mangement of orofacial herpes simplex
infections (herpetic gingivostomatitis, herpes labialis)
• INTERFERONS- are naturally produced protein with
potent antiviral activity
• Spectrum activity- hepatitis B & C virus
• Adverse effect- flu-like symptom.

22. Important antiviral agents
Interfere with DNA/RNA
Aciclovir Herpes simplex virus
Ganciclovir Cytomegalovirus
Zidovudine Human immunodeficiency v.
Ribavirin Respiratory syncytial virus
Interfere with virus
uncoating
amentidine Influenza type a virus
Interferon ά Hepatitis B and C virus

23. Antimicrobial Drug Resistance
Principles and Definitions
• Some species of bacteria are innately resist to certain
antibiotic.
• Some strains may develop or acquire resistance to
particular antibiotics.
• Acquired resistance may arise by a single, spontaneous
chromosome mutation .
• Bacteria can acquire resistance genes via plasmids
• An individual plasmid may code for resistance to several
types of antibiotics

24. Antimicrobial Drug Resistance
Mechanisms
• Altered target- target enzyme may change perhaps by
mutation.( penicillin binding protein)
– Alteration in access to the target site (altered uptake)- through
change permeability or by actively pumping the drug out of the cell
(tetracycline)
– Drug inactivation- enzyme may produced that inactivate the
antibacterial agent. beta lactamase)