2. OUTLINE
a. Bacterial cell structure
b. Antibiotic groups and sites of action
c. Mechanisms of Resistance in Bacteria
d. Sensitivity testing
3. Principles and Definitions
• Selectivity
– Selectivetoxicity
• Therapeutic index
– Toxic dose/ Effective dose
• Categories of antibiotics
– Bactericidal
• Usually antibiotic of choice
– Bacteriostatic
• Duration of treatment sufficient for host
defenses
4. Principles and Definitions
• Antibiotic susceptibility testing (in vitro)
– Minimum inhibitory concentration (MIC)
• Lowest concentration that results in inhibition of
visible growth
– Minimum bactericidal concentration (MBC)
• Lowest concentration that kills 99.9% of the
original inoculum
5.
6.
7. Inhibitors of cell wall synthesis
A Beta lactam antibiotics
Penicillins
Cephalosporins
B Glycopeptides
C Bacitracin
spheroplasts and protoplasts
10. Inhibitors of Cell Membrane function
1. Detergents: Colistin and Polymyxins
2. Inhibition of Biosynthetic Functions:
Nalidixic acid and Novobiocin Polyenes
3. Ionophores: eg K+ loss
Antifungals
11. Inhibitors of protein synthesis
70S versus 80S ribosomes
30S
AMINOGLYCOSIDES
TETRACYCLINES
OXAZOLIDINONES
50S
CHLORAMPHENICOL
MACROLIDES
LINCOMYCIN
12. Protein Synthesis Inhibitors
• Mostly bacteriostatic
• Selectivity due to differences in
prokaryotic and eukaryotic ribosomes
• Some toxicity -
13. • Aminoglycosides
1 receptor attachment
2 prevents formation of initiation
complex
3 misreading
4 polysomes break into monosomes
14.
15. Inhibition of Nucleic Acid
Synthesis
DNA
• Quinolones DNA gyrase
• Sulfonamides
• Trimethoprim
RNA
• Rifampicin RNA polymerase
16. Inhibitors of RNA Synthesis
Selectivity due to differences between
prokaryotic and eukaryotic RNA polymerase
17. Inhibitors of DNA Synthesis
Selectivity due to differences between
prokaryotic and eukaryotic enzymes
18. Quinolones (bactericidal)
nalidixic acid, ciprofloxacin, ofloxacin, norfloxacin,
levofloxacin, lomefloxacin, sparfloxacin
• Mode of action - These antimicrobials bind to the A subunit of
DNA gyrase (topoisomerase) and prevent supercoiling of DNA,
thereby inhibiting DNA synthesis.
• Spectrum of activity - Gram-positive cocci and urinary tract
infections
• Resistance - Common for nalidixic acid; developing for
ciprofloxacin
19. Rifampin, Rifamycin,
Rifampicin, Rifabutin (bactericidal)
• Mode of action - These antimicrobials bind to DNA-dependent
RNA polymerase and inhibit initiation of mRNA synthesis.
• Spectrum of activity - Broad spectrum but is used most
commonly in the treatment of tuberculosis
• Resistance - Common
• Combination therapy - Since resistance is common, rifampin
is usually used in combination therapy.
30. Antibiotic susceptibility testing
(in vitro)
Minimum inhibitory concentration (MIC)
Lowest concentration that results in inhibition of
visible growth
Minimum bactericidal concentration (MBC)
Lowest concentration that kills 99.9% of the
original inoculum
38. Review
• Sites of action
• Mechanisms of action
• Major groups
• Sensitivity testing methodology
Editor's Notes
Prokaryotic cell
Selective permeability barrier and active trnsport. Damage leads to loss of macromolecules and ions.
Ionophores: discharge of membrane potential and loss of oxidative phosphorylation.(Valinomycin)
