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Antibiotics
This document discusses antibiotics and their mechanisms of action. It describes how antibiotics target bacterial cell structures like the cell wall and membrane, as well as intracellular components like protein and nucleic acid synthesis. The major groups of antibiotics are outlined, including how they inhibit cell wall synthesis, membrane function, protein production, and nucleic acid replication. Mechanisms of antibiotic resistance in bacteria are also reviewed. The document concludes by explaining methods for determining antibiotic susceptibility, including minimum inhibitory concentration and disk diffusion tests.
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Antibiotics
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- 2. OUTLINE a. Bacterial cellstructure b. Antibiotic groups and sites of action c. Mechanisms of Resistance in Bacteria d. Sensitivity testing
- 3. Principles and Definitions •Selectivity – Selective toxicity • 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
- 7. Inhibitors of cellwall synthesis A Beta lactam antibiotics Penicillins Cephalosporins B Glycopeptides C Bacitracin spheroplasts and protoplasts
- 8. Cytoplasm Lipoteichoic acid Peptidoglycan-teichoicacid Cytoplasmic membrane GRAM POSITIVE CELL ENVELOPE Degradative enzyme
- 9. GRAM NEGATIVE CELL ENVELOPE Cytoplasm Inner(cytoplasmic) membrane Outer Membrane (Major permeability barrier) LipopolysaccharidePorin Braun lipoprotein Degradative enzyme Periplasmic binding protein Permease
- 10. Inhibitors of CellMembrane 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 proteinsynthesis 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 receptorattachment 2 prevents formation of initiation complex 3 misreading 4 polysomes break into monosomes
- 15. Inhibition of NucleicAcid Synthesis DNA • Quinolones DNA gyrase • Sulfonamides • Trimethoprim RNA • Rifampicin RNA polymerase
- 16. Inhibitors of RNASynthesis Selectivity due to differences between prokaryotic and eukaryotic RNA polymerase
- 17. Inhibitors of DNASynthesis 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.
- 20. Inhibitors of FolicAcid Synthesis • Basis of Selectivity • Review of Folic Acid Metabolism p-aminobenzoic acid + Pteridine Dihydropteroic acid Dihydrofolic acid Tetrahydrofolic acid Pteridine synthetas e Dihydrofolat e synthetase Dihydrofolat e reductase ine Purine s Methionin e Trimethoprim Sulfonamide
- 21. • Most antimicrobialshave more than one mechanism of action.
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- 24. Mechanism of Actionof Beta-lactams
- 25. Penicilllin, action of b-lactamase Siteof amidase action Site of penicillinase action (break in b-lactam ring)
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- 30. Antibiotic susceptibility testing (invitro) 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
- 31. Antibiotic Susceptibility Testing 8 402 1 Tetracycline ( g/ml) MIC = 2 g/ml Determination of MIC Chl Amp Ery Str Tet Disk Diffusion Test
- 32. Media used forSensitivity Testing • Mueller Hinton Agar • DST • Special media e.g. Chocolate agar
- 33. Disc Diffusion Testing •A. Kirby Bauer method…… CLSI recommended • B. Stokes Comparitive method
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- 36. MIC evaluation byE test
- 37. • Inoculum Standardization 0.5McFarland Standard
- 38. Review • Sites ofaction • Mechanisms of action • Major groups • Sensitivity testing methodology