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Antimicrobial Drugs. Chapter 20:. Antimicrobial Drugs: Antibiotic : Substance produced by a microorganism that in small amounts inhibits the growth of another microbe. Antibiotic producing microbes include: Gram-Positive Rods : Bacillus subtilis : Bacitracin Bacillus polymyxa : Polymyxin

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Antimicrobial Drugs

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    1. Antimicrobial Drugs Chapter 20:

    2. Antimicrobial Drugs: Antibiotic: Substance produced by a microorganism that in small amounts inhibits the growth of another microbe. Antibiotic producing microbes include: • Gram-Positive Rods: • Bacillus subtilis: Bacitracin • Bacillus polymyxa: Polymyxin • Fungi • Penicillium notatum: Penicillin • Cephalosporium spp.: Cephalothin • Actinomycetes: • Streptomyces venezuelae: Chloramphenicol • Streptomyces griseus: Streptomycin • Streptomyces nodosus: Amphotericin B • Micromonospora purpurea: Gentamycin

    3. Penicillium Colony Inhibits Bacterial Growth

    4. Antibacterials: Relatively easy to develop and find with low toxicity because procaryotic cells are very different from host cells. • Antihelminthic, antiprotozoan, andantifungal drugs: More difficult to develop because eucaryotic cells resemble human cells. • Antivirals: Most difficult to develop because virus reproduces using host cell enzymes and machinery. Spectrum of Antimicrobial Activity • Broad Spectrum: Effective against many different types of bacteria (e.g.: both gram positive and negative). Examples: Tetracyclin • Narrow Spectrum Antibiotics: Effective against a subset of bacteria (either gram positive and negative). Examples: Penicillin, Isoniazid (Mycobacteria only}

    5. Mechanisms of Action of Antibiotics

    6. Antimicrobial Mechanisms of Action • Inhibition of Cell Wall Synthesis: Interfere with peptidoglycan synthesis. • Result in cell lysis. • Low toxicity. • E.g.: Penicillin and vancomycin. Other antibiotics in the penicillin family (B-lactams): Ampicillin, Methicillin, and Oxacillin

    7. Structure of Penicillin and Related Antibiotics

    8. Penicillinase and Penicillin Resistance

    9. Antimicrobial Mechanisms of Action • Inhibition of Protein Synthesis: Interfere with procaryotic (70S) ribosomes, also found in mitochondria. • Most have broad spectrum of activity • Tetracyclin, chloramphenicol, erythromycin, and streptomycin.

    10. Chloramphenicol and Tetracycline Inhibit Protein Synthesis

    11. Chloramphenicol Inhibits Protein Synthesis

    12. Antimicrobial Mechanisms of Action • Injury to the Plasma Membrane: Cause changes in membrane permeability. • Result in loss of metabolites and/or cell lysis. • Many polypeptide antibiotics. • E.g.: Polymyxin B (antibacterial) or miconazole (antifungal). • Inhibition of Nucleic Acid (DNA/RNA) Synthesis: Interfere with DNA replication and transcription. • May be toxic to human cells. • E.g.: Rifampin and quinolones..

    13. Antimicrobial Mechanisms of Action • Inhibition of Synthesis of Essential Metabolites: Involve competitive inhibition of key enzymes. • Closely resemble substrate of enzyme. • E.g.: Sulfa drugs inhibit the synthesis of folic acid which is necessary for DNA and RNA synthesis.

    14. Sulfa Drugs Inhibit Folic Acid Synthesis

    15. Safety Concerns with the Use of Antimicrobials: • Toxicity • Kidney damage • Liver damage • Bone marrow (Chloramphenicol and aplastic anemia) • Interactions with other medications • May neutralize effectiveness of contraceptive pills • Hypersensitivity reactions • Anaphylactic reactions to penicillin • Triple antibiotic ointment (rashes & neomycin B) • Fetal damage/risk to pregnant women • Tetracyclin causes discoloration of teeth in children and may cause liver damage in pregnant women • Fluoroquinolones may cause cartilage damage. • Dysbiosis: Host’s normal beneficial flora killed off, causing various symptoms such as diarrhea, digestive problems (constipation, gas), yeast infections, etc. Probiotics and antifungals can help. • Antibiotic Resistance: Multiple antibiotic resistant is becoming a huge problem. MRSA= Methicillin Resistant Staphylococcus aureus.

    16. Fluoroquinolone Resistant Campylobacter jejuni in U.S.